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Sample records for hippocampal injury atrophy

  1. Extent of hippocampal atrophy predicts degree of deficit in recall.

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    Patai, Eva Zita; Gadian, David G; Cooper, Janine M; Dzieciol, Anna M; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2015-10-13

    Which specific memory functions are dependent on the hippocampus is still debated. The availability of a large cohort of patients who had sustained relatively selective hippocampal damage early in life enabled us to determine which type of mnemonic deficit showed a correlation with extent of hippocampal injury. We assessed our patient cohort on a test that provides measures of recognition and recall that are equated for difficulty and found that the patients' performance on the recall tests correlated significantly with their hippocampal volumes, whereas their performance on the equally difficult recognition tests did not and, indeed, was largely unaffected regardless of extent of hippocampal atrophy. The results provide new evidence in favor of the view that the hippocampus is essential for recall but not for recognition.

  2. Evaluating Alzheimer's disease progression using rate of regional hippocampal atrophy.

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    Full Text Available Alzheimer's disease (AD is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects.

  3. Deficits in memory and visuospatial learning correlate with regional hippocampal atrophy in MS.

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    Longoni, Giulia; Rocca, Maria A; Pagani, Elisabetta; Riccitelli, Gianna C; Colombo, Bruno; Rodegher, Mariaemma; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

    2015-01-01

    The hippocampus has a critical role in episodic memory and visuospatial learning and consolidation. We assessed the patterns of whole and regional hippocampal atrophy in a large group of multiple sclerosis (MS) patients, and their correlations with neuropsychological impairment. From 103 MS patients and 28 healthy controls (HC), brain dual-echo and high-resolution 3D T1-weighted images were acquired using a 3.0-Tesla scanner. All patients underwent a neuropsychological assessment of hippocampal-related cognitive functions, including Paired Associate Word Learning, Short Story, delayed recall of Rey-Osterrieth Complex Figure and Paced Auditory Serial Attention tests. The hippocampi were manually segmented and volumes derived. Regional atrophy distribution was assessed using a radial mapping analysis. Correlations between hippocampal atrophy and clinical, neuropsychological and MRI metrics were also evaluated. Hippocampal volume was reduced in MS patients vs HC (p right and hippocampus). In MS patients, radial atrophy affected CA1 subfield and subiculum of posterior hippocampus, bilaterally. The dentate hilus (DG:H) of the right hippocampal head was also affected. Regional hippocampal atrophy correlated with brain T2 and T1 lesion volumes, while no correlation was found with disability. Damage to the CA1 and subiculum was significantly correlated to the performances at hippocampal-targeted neuropsychological tests. These results show that hippocampal subregions have a different vulnerability to MS-related damage, with a relative sparing of the head of the left hippocampus. The assessment of regional hippocampal atrophy may help explain deficits of specific cognitive functions in MS patients, including memory and visuospatial abilities.

  4. Porencephaly in dogs and cats: relationships between magnetic resonance imaging (MRI) features and hippocampal atrophy.

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    Hori, Ai; Hanazono, Kiwamu; Miyoshi, Kenjirou; Nakade, Tetsuya

    2015-07-01

    Porencephaly is the congenital cerebral defect and a rare malformation and described few MRI reports in veterinary medicine. MRI features of porencephaly are recognized the coexistence with the unilateral/bilateral hippocampal atrophy, caused by the seizure symptoms in human medicine. We studied 2 dogs and 1 cat with congenital porencephaly to characterize the clinical signs and MRI, and to discuss the associated MRI with hippocampal atrophy. The main clinical sign was the seizure symptoms, and all had hippocampal atrophy at the lesion side or the larger defect side. There is association between hippocampal atrophy or the cyst volume and the severe of clinical signs, and it is suggested that porencephaly coexists with hippocampal atrophy as well as humans in this study.

  5. Progressive contralateral hippocampal atrophy following surgery for medically refractory temporal lobe epilepsy.

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    Elliott, Cameron A; Gross, Donald W; Wheatley, B Matt; Beaulieu, Christian; Sankar, Tejas

    2016-09-01

    Determine the extent and time course of volumetric changes in the contralateral hippocampus following surgery for medically refractory temporal lobe epilepsy (TLE). Serial T1-weighted MRI brain scans were obtained in 26 TLE patients pre- and post-temporal lobe epilepsy surgery as well as in 12 control subjects of similar age. Patients underwent either anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH). Blinded, manual hippocampal volumetry (head, body, and tail) was performed in two groups: 1) two scan group [ATL (n=6); SAH (n=10)], imaged pre-surgery and on average at 5.4 years post-surgery; and 2) longitudinal group [ATL (n=8); SAH (n=2)] imaged pre-surgery and on post-operative day 1, 2, 3, 6, 60, 120 and a delayed time point (average 2.4 years). In the two scan group, there was atrophy by 12% of the unresected contralateral hippocampus (p<0.001), with atrophy being most pronounced (27%) in the hippocampal body (p<0.001) with no significant differences seen for the hippocampal head or tail. In the longitudinal group, significant atrophy was also observed for the whole hippocampus and the body with atrophy seen as early as post-operative day #1 which progressed significantly over the first post-operative week (1.3%/day and 3.0%./day, respectively) before stabilizing over the long-term to a 13% reduction in total volume. There was no significant difference in atrophy compared by surgical approach (ATL vs. SAH; p=0.94) or side (p=0.31); however, atrophy was significantly more pronounced in patients with ongoing post-operative seizures (hippocampal body, p=0.019; whole hippocampus, p=0.048). There were no detectable post-operative neuropsychological deficits attributable to contralateral hippocampal atrophy. Significant contralateral hippocampal atrophy occurs following TLE surgery, which begins immediately and progresses over the first post-operative week. The observation that seizure free patients had significantly less atrophy of the

  6. Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging

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    Seibert, Tyler M.; Karunamuni, Roshan [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Bartsch, Hauke [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Kaifi, Samar [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Krishnan, Anitha Priya [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Dalia, Yoseph; Burkeen, Jeffrey; Murzin, Vyacheslav; Moiseenko, Vitali [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Kuperman, Joshua; White, Nathan S. [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Brewer, James B. [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Department of Neurosciences, University of California, San Diego, La Jolla, California (United States); Farid, Nikdokht [Department of Radiology, University of California, San Diego, La Jolla, California (United States); McDonald, Carrie R. [Department of Psychiatry, University of California, San Diego, La Jolla, California (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States)

    2017-02-01

    Purpose: After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Methods and Materials: Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3-dimensional volumetric MRI before and 1 year after RT. Images were processed using software with clearance from the US Food and Drug Administration and Conformité Européene marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy 1 year after RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α = 0.05. Results: Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=−0.24, P=.03). Mean hippocampal volume was significantly reduced 1 year after high-dose RT (mean −6%, P=.009) but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (P<.01). Conclusions: The hippocampus demonstrates radiation dose–dependent atrophy after treatment for brain

  7. Potential hippocampal region atrophy in diabetes mellitus type 2. A voxel-based morphometry VSRAD study

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    Kamiyama, Kazutoshi; Sugihara, Masaki; Wada, Akihiko

    2010-01-01

    Among diabetes mellitus type 2 (DM2) patients, the frequency of cognitive dysfunction is higher and the relative risk of Alzheimer's disease (AD) is approximately twice that of nondiabetics. Cognitive impairment symptoms of AD are induced by limbic system dysfunction, and an early-stage AD brain without dementia has the potential for atrophy in the hippocampal region. In this study, we estimated potential hippocampal region atrophy in DM2 and pursued the association between DM2 and cognitive impairment/AD. Voxel-based morphometry analysis was performed in 28 diabetics (14 men, 14 women; ages 59-79 years, mean 70.7 years) and 28 sex- and age- matched (±1 year) nondiabetics. Severity of gray matter loss in the hippocampal region and whole brain were investigated. Group analysis was performed using two-tailed unpaired t-test; significance was assumed with less than 1% (P<0.01) of the critical rate. There was a significant difference between diabetics and nondiabetics regarding the severity of hippocampal region atrophy and whole-brain atrophy. Only diabetics showed a positive correlation for severity of hippocampal region atrophy and whole-brain atrophy (rs=0.69, P<0.0001). Aged DM2 patients have the potential for hippocampal region atrophy, and its dysfunction can be related to the expression of a cognitive impairment that resembles AD. (author)

  8. Neurosyphilis with dementia and bilateral hippocampal atrophy on brain magnetic resonance imaging

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    Mehrabian, S.; Raycheva, M.; Traykova, M.; Stankova, T.; Penev, L.; Georgieva-Kozarova, G.; Grigorova, O.; Traykov, L.

    2012-01-01

    Full text: Background: This article reports a rare case of active neurosyphilis in a 33-years-old man with mild to moderate dementia and marked hippocampal atrophy, mimicking early onset Alzheimer's disease. Few number of cases described bilateral hippocampal atrophy mimicking Alzheimer's disease in neurosyphilis. Case presentation: The clinical feature is characterized by a progressive cognitive decline and behavioral changes for the last 18 months. Neuropsychological examination revealed mild to moderate dementia (MMSE=16) with impaired memory, attention and executive dysfunction. Pyramidal, extrapyramidal signs, dysarthria and impairment in coordination were documented. Brain magnetic resonance imaging showed cortical atrophy with marked bilateral hippocampal atrophy. The diagnosis of active neurosyphilis was based on positive results of Venereal Disease Research Laboratory test - Treponema Pallidum. Hemagglutination reactions in blood and cerebrospinal fluid samples. In addition, cerebrospinal fluid analysis showed pleocytosis and elevated protein levels. High dose intravenous penicillin therapy was administered. During the follow up examination at 6 month, the clinical signs, and neuropsychological examinations, and cerebrospinal fluid samples showed improvement. Conclusion: This case underlines the importance of early diagnosis of neurosyphilis. The results suggest that neurosyphilis should be considered when magnetic resonance imaging results indicate mesiotemporal abnormalities and hippocampal atrophy. Neurosyphilis is a treatable condition and needs early aggressive antibiotic therapy

  9. Bilateral hippocampal atrophy in temporal lobe epilepsy: Effect of depressive symptoms and febrile seizures

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    Finegersh, Andrey; Avedissian, Christina; Shamim, Sadat; Dustin, Irene; Thompson, Paul M.; Theodore, William H.

    2011-01-01

    Summary Purpose Neuroimaging studies suggest a history of febrile seizures, and depression, are associated with hippocampal volume reductions in patients with temporal lobe epilepsy (TLE). Methods We used radial atrophy mapping (RAM), a three-dimensional (3D) surface modeling tool, to measure hippocampal atrophy in 40 patients with unilateral TLE, with or without a history of febrile seizures and symptoms of depression. Multiple linear regression was used to single out the effects of covariates on local atrophy. Key Findings Subjects with a history of febrile seizures (n = 15) had atrophy in regions corresponding to the CA1 and CA3 subfields of the hippocampus contralateral to seizure focus (CHC) compared to those without a history of febrile seizures (n = 25). Subjects with Beck Depression Inventory II (BDI-II) score ≥14 (n = 11) had atrophy in the superoanterior portion of the CHC compared to subjects with BDI-II <14 (n = 29). Significance Contralateral hippocampal atrophy in TLE may be related to febrile seizures or depression. PMID:21269286

  10. Comparison with hippocampal atrophy and hypoperfusion in Alzheimer's disease

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    Chung, YA; Kim, SH; Chung, SK; Juh, RH; Sohn, HS; Suh, TS; Choe, BY

    2004-01-01

    Objective: Hypoperfusion and hippocampal atropy of the medial temporal lobe are peculiarity of Alzheimer's disease (AD). The manual ROI (region of interest) technique for hippocampal volume estimation is specific and sensitive for the detection of hippocampal atrophy. In patients with AD reported a significant correlation between hippocampal volume and hypoperfusion. This study investigated correlations between atrophy distinct medial temporal lobe structure and hypoperfusion in hippocampal volumetry. Methods: The hippocampi were individually outlined on Tl-weighted volumetry MRI and calculated with MATLAB in 12 patients with AD. All volume measurements were performed by a segmentation technique with a combination of tracing and thresholding. The volume of a given structure in each slice was obtained by automatically counting the number of pixels within the segmented regions and multiplying the number by a voxel size. In order to permit direct regional comparisons, both of each patient's Tc- 99m ECD SPECT was then registered to the patient's MRI. Delineation continued anteriorly in each contiguous slice reaching the head of the hippocampus, which was distinguished from the overlying amygdala by the presence of the alveus or uncal recess. The right hippocampus (RH) was measured first, followed by the left hippocampus (LH). The accuracy of registration was investigated in a validation study with developed brain phantom. Results:The mean total intracranial volume of the AD was significantly smaller volume (1492.9 cm 3 ) and hypo perfused than those in normal subjects. The mean hippocampal volumes were 2.01 cm 3 and l.99 cm 3 for the RH and LH. The correlations between volume and hypoperfusion in the affected hippocampi were found to be significant; especially the medial temporal lobe is markedly hypo perfused. Conclusion: Volumetry is the most sensitive tool for the detection of hippocampal abnormality in AD, and significant correlation between asymmetry in

  11. Hippocampal atrophy and memory dysfunction associated with physical inactivity in community-dwelling elderly subjects: The Sefuri study.

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    Hashimoto, Manabu; Araki, Yuko; Takashima, Yuki; Nogami, Kohjiro; Uchino, Akira; Yuzuriha, Takefumi; Yao, Hiroshi

    2017-02-01

    Physical inactivity is one of the modifiable risk factors for hippocampal atrophy and Alzheimer's disease. We investigated the relationship between physical activity, hippocampal atrophy, and memory using structural equation modeling (SEM). We examined 213 community-dwelling elderly subjects (99 men and 114 women with a mean age of 68.9 years) without dementia or clinically apparent depression. All participants underwent Mini-Mental State Examination (MMSE) and Rivermead Behavioral Memory Test (RBMT). Physical activities were assessed with a structured questionnaire. We evaluated the degree of hippocampal atrophy (z-score-referred to as ZAdvance hereafter), using a free software program-the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) based on statistical parametric mapping 8 plus Diffeomorphic Anatomical Registration Through an Exponentiated Lie algebra. Routine magnetic resonance imaging findings were as follows: silent brain infarction, n  = 24 (11.3%); deep white matter lesions, n  = 72 (33.8%); periventricular hyperintensities, n  = 35 (16.4%); and cerebral microbleeds, n  = 14 (6.6%). Path analysis based on SEM indicated that the direct paths from leisure-time activity to hippocampal atrophy (β = -.18, p  physical inactivity, and hippocampal atrophy appeared to cause memory dysfunction, although we are unable to infer a causal or temporal association between hippocampal atrophy and memory dysfunction from the present observational study.

  12. Is radiological evaluation as good as computer-based volumetry to assess hippocampal atrophy in Alzheimer's disease?

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    Boutet, Claire; Drier, Aurelie; Dormont, Didier; Lehericy, Stephane; Chupin, Marie; Colliot, Olivier; Sarazin, Marie; Mutlu, Gurkan; Pellot, Audrey

    2012-01-01

    Hippocampus volumetry is a useful surrogate marker for the diagnosis of Alzheimer's disease (AD). Our purpose was to compare visual assessment of medial temporal lobe atrophy made by radiologists with automatic hippocampal volume and to compare their performances for the classification of AD, mild cognitive impairment (MCI) and cognitively normal (CN). We studied 30 CN, 30 MCI and 30 AD subjects. Six radiologists with two levels of expertise performed two readings of medial temporal lobe atrophy. Medial temporal lobe atrophy was evaluated on coronal three-dimensional T1-weighted images using Scheltens scale and compared with hippocampal volume obtained using a fully automatic segmentation method (Spearman's rank coefficient). Visual assessment of medial temporal lobe atrophy was correlated with hippocampal volume (p < 0.01). Classification performances between MCI converter and CN was better using volumetry than visual assessment of non-expert readers whereas classification of AD and CN did not differ between visual assessment and volumetry except for the first reading of one non-expert (p = 0.03). Visual assessment of medial temporal lobe atrophy by radiologists was well correlated with hippocampal volume. Radiological assessment is as good as computer-based volumetry for the classification of AD, MCI non-converter and CN and less good for the classification of MCI converter versus CN. Use of Scheltens scale for assessing hippocampal atrophy in AD seems thus justified in clinical routine. (orig.)

  13. Hippocampal atrophy and developmental regression as first sign of linear scleroderma "en coup de sabre".

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    Verhelst, Helene E; Beele, Hilde; Joos, Rik; Vanneuville, Benedicte; Van Coster, Rudy N

    2008-11-01

    An 8-year-old girl with linear scleroderma "en coup de sabre" is reported who, at preschool age, presented with intractable simple partial seizures more than 1 year before skin lesions were first noticed. MRI revealed hippocampal atrophy, controlaterally to the seizures and ipsilaterally to the skin lesions. In the following months, a mental and motor regression was noticed. Cerebral CT scan showed multiple foci of calcifications in the affected hemisphere. In previously reported patients the skin lesions preceded the neurological signs. To the best of our knowledge, hippocampal atrophy was not earlier reported as presenting symptom of linear scleroderma. Linear scleroderma should be included in the differential diagnosis in patients with unilateral hippocampal atrophy even when the typical skin lesions are not present.

  14. Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer's disease

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    Dhikav, Vikas; Duraiswamy, Sharmila; Anand, Kuljeet Singh

    2017-01-01

    Introduction: Hippocampus undergoes atrophy in patients with Alzheimer's disease (AD). Calculation of hippocampal volumes can be done by a variety of methods using T1-weighted images of magnetic resonance imaging (MRI) of the brain. Medial temporal lobes atrophy (MTL) can be rated visually using T1-weighted MRI brain images. The present study was done to see if any correlation existed between hippocampal volumes and visual rating scores of the MTL using Scheltens Visual Rating Method. Materia...

  15. Is radiological evaluation as good as computer-based volumetry to assess hippocampal atrophy in Alzheimer's disease?

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    Boutet, Claire; Drier, Aurelie; Dormont, Didier; Lehericy, Stephane [Groupe Hospitalier Pitie-Salpetriere, Department of Neuroradiology, AP-HP, Paris Cedex 13 (France); Universite Pierre et Marie Curie-Paris 6, Centre de Recherche de l' Institut du Cerveau et de la Moelle epiniere, UMR-S975, Paris (France); Inserm, Paris (France); CNRS, Paris (France); ICM-Institut du Cerveau et de la Moelle epiniere, Paris (France); Chupin, Marie; Colliot, Olivier [Universite Pierre et Marie Curie-Paris 6, Centre de Recherche de l' Institut du Cerveau et de la Moelle epiniere, UMR-S975, Paris (France); Inserm, Paris (France); CNRS, Paris (France); ICM-Institut du Cerveau et de la Moelle epiniere, Paris (France); Equipe Cogimage-CRICM, Paris Cedex 13 (France); Sarazin, Marie [Universite Pierre et Marie Curie-Paris 6, Centre de Recherche de l' Institut du Cerveau et de la Moelle epiniere, UMR-S975, Paris (France); Inserm, Paris (France); CNRS, Paris (France); ICM-Institut du Cerveau et de la Moelle epiniere, Paris (France); Groupe Hospitalier Pitie-Salpetriere, Department of Neurology, Institut de la Memoire et de la Maladie d' Alzheimer-IM2A, Paris Cedex 13 (France); Mutlu, Gurkan [Groupe Hospitalier Pitie-Salpetriere, Urgences Cerebro-Vasculaires, Universite Pierre et Marie Curie-Paris 6, Paris Cedex 13 (France); Hopital Saint-Louis, Inserm, Universite Paris 7-Denis Diderot, Paris (France); Pellot, Audrey [Groupe Hospitalier Pitie-Salpetriere, Department of Neuroradiology, AP-HP, Paris Cedex 13 (France); Collaboration: And the Alzheimer' s Disease Neuroimaging Initiative

    2012-12-15

    Hippocampus volumetry is a useful surrogate marker for the diagnosis of Alzheimer's disease (AD). Our purpose was to compare visual assessment of medial temporal lobe atrophy made by radiologists with automatic hippocampal volume and to compare their performances for the classification of AD, mild cognitive impairment (MCI) and cognitively normal (CN). We studied 30 CN, 30 MCI and 30 AD subjects. Six radiologists with two levels of expertise performed two readings of medial temporal lobe atrophy. Medial temporal lobe atrophy was evaluated on coronal three-dimensional T1-weighted images using Scheltens scale and compared with hippocampal volume obtained using a fully automatic segmentation method (Spearman's rank coefficient). Visual assessment of medial temporal lobe atrophy was correlated with hippocampal volume (p < 0.01). Classification performances between MCI converter and CN was better using volumetry than visual assessment of non-expert readers whereas classification of AD and CN did not differ between visual assessment and volumetry except for the first reading of one non-expert (p = 0.03). Visual assessment of medial temporal lobe atrophy by radiologists was well correlated with hippocampal volume. Radiological assessment is as good as computer-based volumetry for the classification of AD, MCI non-converter and CN and less good for the classification of MCI converter versus CN. Use of Scheltens scale for assessing hippocampal atrophy in AD seems thus justified in clinical routine. (orig.)

  16. Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis

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    Miller, T; Chong, T; Aimola Davies, A; Ng, T; Johnson, M; Irani, S; Vincent, A; Husain, M; Jacob, S; Maddison, P; Kennard, C; Gowland, P; Rosenthal, C

    2017-01-01

    Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0....

  17. Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis.

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    Miller, Thomas D; Chong, Trevor T-J; Aimola Davies, Anne M; Ng, Tammy W C; Johnson, Michael R; Irani, Sarosh R; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A; Rosenthal, Clive R

    2017-05-01

    Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P 3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  18. Differential Atrophy of Hippocampal Subfields: A Comparative Study of Dementia with Lewy Bodies and Alzheimer Disease.

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    Mak, Elijah; Su, Li; Williams, Guy B; Watson, Rosie; Firbank, Michael; Blamire, Andrew; O'Brien, John

    2016-02-01

    Dementia with Lewy bodies (DLB) is characterized by relative preservation of the medial temporal lobe compared with Alzheimer disease (AD). The differential involvement of the hippocampal subfields in both diseases has not been clearly established, however. We aim to investigate hippocampal subfield differences in vivo in a clinical cohort of DLB and AD subjects. 104 participants (35 DLBs, 36 ADs, and 35 healthy comparison [HC] subjects) underwent clinical assessment and 3T T1-weighted imaging. A Bayesian model implemented in Freesurfer was used to automatically segment the hippocampus and its subfields. We also examined associations between hippocampal subfields and tests of memory function. Both the AD and DLB groups demonstrated significant atrophy of the total hippocampus relative to HC but the DLB group was characterized by preservation of the cornu ammonis 1 (CA1), fimbria, and fissure. In contrast, all the hippocampal subfields except the fissure were significantly atrophied in AD compared with both DLB and HC groups. Among DLB subjects, CA1 was correlated with the Recent Memory score of the CAMCOG and Delayed Recall subscores of the HVLT. DLB is characterized by milder hippocampal atrophy that was accompanied by preservation of the CA1. The CA1 was also associated with memory function in DLB. Our findings highlight the promising role of hippocampal subfield volumetry, particularly that of the CA1, as a biomarker for the distinction between AD and DLB. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Hippocampal atrophy in people with memory deficits: results from the population-based IPREA study.

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    Ferrarini, Luca; van Lew, Baldur; Reiber, Johan H C; Gandin, Claudia; Galluzzo, Lucia; Scafato, Emanuele; Frisoni, Giovanni B; Milles, Julien; Pievani, Michela

    2014-07-01

    Clinical studies have shown that hippocampal atrophy is present before dementia in people with memory deficits and can predict dementia development. The question remains whether this association holds in the general population. This is of interest for the possible use of hippocampal atrophy to screen population for preventive interventions. The aim of this study was to assess hippocampal volume and shape abnormalities in elderly adults with memory deficits in a cross-sectional population-based study. We included individuals participating in the Italian Project on the Epidemiology of Alzheimer Disease (IPREA) study: 75 cognitively normal individuals (HC), 31 individuals with memory deficits (MEM), and 31 individuals with memory deficits not otherwise specified (MEMnos). Hippocampal volumes and shape were extracted through manual tracing and the growing and adaptive meshes (GAMEs) shape-modeling algorithm. We investigated between-group differences in hippocampal volume and shape, and correlations with memory deficits. In MEM participants, hippocampal volumes were significantly smaller than in HC and were mildly associated with worse memory scores. Memory-associated shape changes mapped to the anterior hippocampus. Shape-based analysis detected no significant difference between MEM and HC, while MEMnos showed shape changes in the posterior hippocampus compared with HC and MEM groups. These findings support the discriminant validity of hippocampal volumetry as a biomarker of memory impairment in the general population. The detection of shape changes in MEMnos but not in MEM participants suggests that shape-based biomarkers might lack sensitivity to detect Alzheimer's-like pathology in the general population.

  20. Neonatal hypoxia, hippocampal atrophy, and memory impairment: evidence of a causal sequence.

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    Cooper, Janine M; Gadian, David G; Jentschke, Sebastian; Goldman, Allan; Munoz, Monica; Pitts, Georgia; Banks, Tina; Chong, W Kling; Hoskote, Aparna; Deanfield, John; Baldeweg, Torsten; de Haan, Michelle; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2015-06-01

    Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life. © The Author 2013. Published by Oxford University Press.

  1. Frequent seizures are associated with a network of gray matter atrophy in temporal lobe epilepsy with or without hippocampal sclerosis.

    Directory of Open Access Journals (Sweden)

    Ana C Coan

    Full Text Available OBJECTIVE: Patients with temporal lobe epilepsy (TLE with hippocampal sclerosis (HS have diffuse subtle gray matter (GM atrophy detectable by MRI quantification analyses. However, it is not clear whether the etiology and seizure frequency are associated with this atrophy. We aimed to evaluate the occurrence of GM atrophy and the influence of seizure frequency in patients with TLE and either normal MRI (TLE-NL or MRI signs of HS (TLE-HS. METHODS: We evaluated a group of 172 consecutive patients with unilateral TLE-HS or TLE-NL as defined by hippocampal volumetry and signal quantification (122 TLE-HS and 50 TLE-NL plus a group of 82 healthy individuals. Voxel-based morphometry was performed with VBM8/SPM8 in 3T MRIs. Patients with up to three complex partial seizures and no generalized tonic-clonic seizures in the previous year were considered to have infrequent seizures. Those who did not fulfill these criteria were considered to have frequent seizures. RESULTS: Patients with TLE-HS had more pronounced GM atrophy, including the ipsilateral mesial temporal structures, temporal lobe, bilateral thalami and pre/post-central gyri. Patients with TLE-NL had more subtle GM atrophy, including the ipsilateral orbitofrontal cortex, bilateral thalami and pre/post-central gyri. Both TLE-HS and TLE-NL showed increased GM volume in the contralateral pons. TLE-HS patients with frequent seizures had more pronounced GM atrophy in extra-temporal regions than TLE-HS with infrequent seizures. Patients with TLE-NL and infrequent seizures had no detectable GM atrophy. In both TLE-HS and TLE-NL, the duration of epilepsy correlated with GM atrophy in extra-hippocampal regions. CONCLUSION: Although a diffuse network GM atrophy occurs in both TLE-HS and TLE-NL, this is strikingly more evident in TLE-HS and in patients with frequent seizures. These findings suggest that neocortical atrophy in TLE is related to the ongoing seizures and epilepsy duration, while thalamic

  2. A cross-sectional MRI study of brain regional atrophy and clinical characteristics of temporal lobe epilepsy with hippocampal sclerosis.

    LENUS (Irish Health Repository)

    2012-02-01

    PURPOSE: Applying a cross-sectional design, we set out to further characterize the significance of extrahippocampal brain atrophy in a large sample of \\'sporadic\\' mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). By evaluating the influence of epilepsy chronicity on structural atrophy, this work represents an important step towards the characterization of MRI-based volumetric measurements as genetic endophenotypes for this condition. METHODS: Using an automated brain segmentation technique, MRI-based volume measurements of several brain regions were compared between 75 patients with \\'sporadic\\' MTLE+HS and 50 healthy controls. Applying linear regression models, we examined the relationship between structural atrophy and important clinical features of MTLE+HS, including disease duration, lifetime number of partial and generalized seizures, and history of initial precipitating insults (IPIs). RESULTS: Significant volume loss was detected in ipsilateral hippocampus, amygdala, thalamus, and cerebral white matter (WM). In addition, contralateral hippocampal and bilateral cerebellar grey matter (GM) volume loss was observed in left MTLE+HS patients. Hippocampal, amygdalar, and cerebral WM volume loss correlated with duration of epilepsy. This correlation was stronger in patients with prior IPIs history. Further, cerebral WM, cerebellar GM, and contralateral hippocampal volume loss correlated with lifetime number of generalized seizures. CONCLUSION: Our findings confirm that multiple brain regions beyond the hippocampus are involved in the pathogenesis of MTLE+HS. IPIs are an important factor influencing the rate of regional atrophy but our results also support a role for processes related to epilepsy chronicity. The consequence of epilepsy chronicity on candidate brain regions has important implications on their application as genetic endophenotypes.

  3. Hippocampal damage and memory impairment in congenital cyanotic heart disease.

    Science.gov (United States)

    Muñoz-López, Mónica; Hoskote, Aparna; Chadwick, Martin J; Dzieciol, Anna M; Gadian, David G; Chong, Kling; Banks, Tina; de Haan, Michelle; Baldeweg, Torsten; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2017-04-01

    Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. To test the generalizability of this causal sequence, we examined a cohort of 41 children aged 8-16, who, having received the arterial switch operation to correct for transposition of the great arteries, had sustained significant neonatal cyanosis but were otherwise neurodevelopmentally normal. As predicted, the cohort had significant bilateral reduction of hippocampal volumes relative to the volumes of 64 normal controls. They also had significant, yet selective, impairment of episodic memory as measured by standard tests of memory, despite relatively normal levels of intelligence, academic attainment, and verbal fluency. Across the cohort, degree of memory impairment was correlated with degree of hippocampal atrophy suggesting that even as early as neonatal life no other structure can fully compensate for hippocampal injury and its special role in serving episodic long term memory. © 2017 Wiley Periodicals, Inc. © 2017 The Authors. Hippocampus Published by Wiley Periodicals, Inc.

  4. Hippocampal Atrophy Is Associated with Altered Hippocampus-Posterior Cingulate Cortex Connectivity in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

    Science.gov (United States)

    Shih, Y C; Tseng, C E; Lin, F-H; Liou, H H; Tseng, W Y I

    2017-03-01

    Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized β = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized β = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity ( F 2,12 = 0.284, P = .757, R 2

  5. Five-year retrospective changes in hippocampal atrophy and cognitive screening test performances in very mild Alzheimer's disease: the Tajiri Project

    International Nuclear Information System (INIS)

    Yamaguchi, S.; Meguro, K.; Shimada, M.; Ishizaki, J.; Yamadori, A.; Sekita, Y.

    2002-01-01

    The medial temporal lobe, especially the hippocampus, is important for normal cognitive function, especially for memory, and is the region with the earliest and most extensive pathological changes in Alzheimer's disease (AD). We investigated the atrophic changes of the hippocampus over a 5-year period and its relation to cognitive screening test performances in normal elderly subjects, those with very mild AD, and patients with AD. Fifty-seven elderly subjects without a moderate or greater degree of cerebrovascular disease as shown by MRI were randomly selected from the town of Tajiri. Thirty-three subjects with a clinical dementia rating (CDR) of 0 (normal), 18 CDR-0.5 (very mild AD) subjects, and six CDR-1 and 2 (AD) subjects underwent MRI and the Mini Mental State Examination (MMSE) twice during the period. Retrospective changes in the hippocampal width and the MMSE scores were evaluated. There were significant CDR group effects for the changes in the mean bilateral hippocampal widths and the MMSE scores. Normal subjects did not show cognitive decline, although there was a slight tendency for hippocampal atrophy. A significant and meaningful Spearman's correlation was noted between left hippocampal atrophy and the MMSE scores over the 5-year period for the CDR-0.5 group. These CDR-0.5 subjects met the MCI (mild cognitive impairment) criteria as proposed by the consensus paper. Findings suggested that normal elderly subjects maintain a high level of cognitive functions for at least 5 years, although hippocampal atrophy might occur. Atrophic change of the left hippocampus might be a good marker of the very early stage of AD. (orig.)

  6. Impaired emotional autobiographical memory associated with right amygdalar-hippocampal atrophy in Alzheimer's disease patients.

    Science.gov (United States)

    Philippi, Nathalie; Botzung, Anne; Noblet, Vincent; Rousseau, François; Després, Olivier; Cretin, Benjamin; Kremer, Stéphane; Blanc, Frédéric; Manning, Liliann

    2015-01-01

    We studied the influence of emotions on autobiographical memory (AbM) in patients with Alzheimer's disease (AD), characteristically triggering atrophy in the hippocampus and the amygdala, two crucial structures sustaining memory and emotional processing. Our first aim was to analyze the influence of emotion on AbM in AD patients, on both the proportion and the specificity of emotional memories. Additionally, we sought to determine the relationship of emotional AbM to amygdalar-hippocampal volumes. Eighteen prodromal to mild AD patients and 18 age-matched healthy controls were included. We obtained 30 autobiographical memories per participant using the modified Crovitz test (MCT). Analyses were performed on global scores, rates and specificity scores of the emotional vs. neutral categories of memories. Amygdalar-hippocampal volumes were extracted from 3D T1-weighted MRI scans and tested for correlations with behavioral data. Overall, AD patients displayed a deficit in emotional AbMs as they elicited less emotional memories than the controls, however, the specificity of those memories was preserved. The deficit likely implied retrieval or storage as it was extended in time and without reminiscence bump effect. Global scores and rates of emotional memories, but not the specificity scores, were correlated to right amygdalar and hippocampal volumes, indicating that atrophy in these structures has a central role in the deficit observed. Conversely, emotional memories were more specific than neutral memories in both groups, reflecting an enhancement effect of emotion that could be supported by other brain regions that are spared during the early stages of the disease.

  7. Intellectual impairment and brain MRI findings in myotonic dystrophy. With a special reference to hippocampal atrophy and white matter lesions

    International Nuclear Information System (INIS)

    Kato, Etsuko; Takahashi, Satoshi; Yonezawa, Hisashi

    1995-01-01

    We performed a correlative study between intellectual impairment, CTG repeat expansion and magnetic resonance imaging (MRI) abnormalities, including hippocampal atrophy, white matter lesions and ventricular dilatation in 15 patients with myotonic dystrophy (MD). They included 4 males and 11 females aged from 20 to 66 years, averaging 43 years of age and 15 years of duration of illness. Nine patients had intellectual impairment (WAIS-R<80). Negative correlations were found between full scale IQ (FSIQ), duration of illness (p<0.05) and CTG repeat expansion (p<0.05). Compared with normal controls, the patients with MD showed a significant reduction in size of the hippocampal head (p<0.01), which was positively correlated to FSIQ, verbal IQ and performance IQ levels (p<0.05). Ten patients had white matter lesions. Severer white matter lesions tended to be recognized in patients with longer duration of illness and with decreased FSIQ level. These results suggest that hippocampal atrophy and white matter lesions are related to intellectual impairment in patients with MD. (author)

  8. Five-year retrospective changes in hippocampal atrophy and cognitive screening test performances in very mild Alzheimer's disease: the Tajiri Project

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, S.; Meguro, K.; Shimada, M.; Ishizaki, J.; Yamadori, A. [Division of Neuropsychology, Department of Disability Medicine, Tohoku University Graduate School of Medicine, Sendai (Japan); Sekita, Y. [Tohoku University Graduate School of Economics, Sendai (Japan)

    2002-01-01

    The medial temporal lobe, especially the hippocampus, is important for normal cognitive function, especially for memory, and is the region with the earliest and most extensive pathological changes in Alzheimer's disease (AD). We investigated the atrophic changes of the hippocampus over a 5-year period and its relation to cognitive screening test performances in normal elderly subjects, those with very mild AD, and patients with AD. Fifty-seven elderly subjects without a moderate or greater degree of cerebrovascular disease as shown by MRI were randomly selected from the town of Tajiri. Thirty-three subjects with a clinical dementia rating (CDR) of 0 (normal), 18 CDR-0.5 (very mild AD) subjects, and six CDR-1 and 2 (AD) subjects underwent MRI and the Mini Mental State Examination (MMSE) twice during the period. Retrospective changes in the hippocampal width and the MMSE scores were evaluated. There were significant CDR group effects for the changes in the mean bilateral hippocampal widths and the MMSE scores. Normal subjects did not show cognitive decline, although there was a slight tendency for hippocampal atrophy. A significant and meaningful Spearman's correlation was noted between left hippocampal atrophy and the MMSE scores over the 5-year period for the CDR-0.5 group. These CDR-0.5 subjects met the MCI (mild cognitive impairment) criteria as proposed by the consensus paper. Findings suggested that normal elderly subjects maintain a high level of cognitive functions for at least 5 years, although hippocampal atrophy might occur. Atrophic change of the left hippocampus might be a good marker of the very early stage of AD. (orig.)

  9. Impaired emotional autobiographical memory associated with right amygdalar-hippocampal atrophy in Alzheimer’s disease patients

    Directory of Open Access Journals (Sweden)

    Nathalie ePHILIPPI

    2015-03-01

    Full Text Available We studied the influence of emotions on autobiographical memory (AbM in patients with Alzheimer’s disease (AD, characteristically triggering atrophy in the hippocampus and the amygdala, two crucial structures sustaining memory and emotional processing. Our first aim was to analyze the influence of emotion on AbM in AD patients, on both the proportion and the specificity of emotional memories. Additionally, we sought to determine the relationship of emotional AbM to amygdalar-hippocampal volumes. Eighteen prodromal to mild AD patients and 18 age-matched healthy controls were included. We obtained 30 autobiographical memories per participant using the modified Crovitz test (MCT. Analyses were performed on global scores, rates and specificity scores of the emotional vs. neutral categories of memories. Amygdalar-hippocampal volumes were extracted from 3D T1-weighted MRI scans and tested for correlations with behavioral data. Overall, AD patients displayed a deficit in emotional AbMs as they elicited less emotional memories than the controls, however, the specificity of those memories was preserved. The deficit likely implied retrieval or storage as it was extended in time and without reminiscence bump effect. Global scores and rates of emotional memories, but not the specificity scores, were correlated to right amygdalar and hippocampal volumes, indicating that atrophy in these structures has a central role in the deficit observed. Conversely, emotional memories were more specific than neutral memories in both groups, reflecting an enhancement effect of emotion that could be supported by other brain regions that are spared during the early stages of the disease.

  10. Influence of APOE Genotype on Hippocampal Atrophy over Time - An N=1925 Surface-Based ADNI Study.

    Directory of Open Access Journals (Sweden)

    Bolun Li

    Full Text Available The apolipoprotein E (APOE e4 genotype is a powerful risk factor for late-onset Alzheimer's disease (AD. In the Alzheimer's Disease Neuroimaging Initiative (ADNI cohort, we previously reported significant baseline structural differences in APOE e4 carriers relative to non-carriers, involving the left hippocampus more than the right--a difference more pronounced in e4 homozygotes than heterozygotes. We now examine the longitudinal effects of APOE genotype on hippocampal morphometry at 6-, 12- and 24-months, in the ADNI cohort. We employed a new automated surface registration system based on conformal geometry and tensor-based morphometry. Among different hippocampal surfaces, we computed high-order correspondences, using a novel inverse-consistent surface-based fluid registration method and multivariate statistics consisting of multivariate tensor-based morphometry (mTBM and radial distance. At each time point, using Hotelling's T(2 test, we found significant morphological deformation in APOE e4 carriers relative to non-carriers in the full cohort as well as in the non-demented (pooled MCI and control subjects at each follow-up interval. In the complete ADNI cohort, we found greater atrophy of the left hippocampus than the right, and this asymmetry was more pronounced in e4 homozygotes than heterozygotes. These findings, combined with our earlier investigations, demonstrate an e4 dose effect on accelerated hippocampal atrophy, and support the enrichment of prevention trial cohorts with e4 carriers.

  11. Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume.

    NARCIS (Netherlands)

    Carmichael, O.; Xie, J.; Fletcher, E.; Singh, B.; DeCarli, C.; Olde Rikkert, M.; et al.,

    2012-01-01

    Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures

  12. Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume

    NARCIS (Netherlands)

    Carmichael, Owen; Xie, Jing; Fletcher, Evan; Singh, Baljeet; Decarli, Charles; A, Saradha; Abdi, Hervé; Abdul Hadi, Normi; Abdulkadir, Ahmed; Abdullah, Afnizanfaizal; Achuthan, Anusha; Adluru, Nagesh; Aggarwal, Namita; Aghajanian, Jania; Agyemang, Alex; Ahdidan, Jamila; Ahmad, Duaa; Ahmed, Shiek; Ahmed, Fareed; Ahmed, Fayeza; Akbarifar, Roshanak; Akhondi-Asl, Alireza; Aksu, Yaman; Alcauter, Sarael; Daniel, Alexander; Alin, Aylin; Alshuft, Hamza; Alvarez-Linera, Juan; Amin-Mansour, Ali; Anderson, Dallas; Anderson, Jeff; Andorn, Anne; Ang, Amma; Angersbach, Steve; Ansarian, Reza; Appaji, Abhishek; Appannah, Arti; Arfanakis, Konstantinos; Armentrout, Steven; Arrighi, Michael; Arumughababu, S. Vethanayaki; Arunagiri, Vidhya; Ashe-McNalley, Cody; Ashford, Wes; Aurelie, Le Page; Avants, Brian; Aviv, Richard; Avula, Ramesh; Richard, Edo; Schmand, Ben

    2012-01-01

    Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures

  13. Regional Hippocampal Atrophy and Higher Levels of Plasma Amyloid-Beta Are Associated With Subjective Memory Complaints in Nondemented Elderly Subjects

    DEFF Research Database (Denmark)

    Cantero, Jose L; Iglesias, Juan E.; Van Leemput, Koen

    2016-01-01

    Background: Evidence suggests a link between the presence of subjective memory complaints (SMC) and lower volume of the hippocampus, one of the first regions to show neuropathological lesions in Alzheimer's disease. However, it remains unknown whether this pattern of hippocampal atrophy is region...

  14. Hippocampal and diencephalic pathology in developmental amnesia.

    Science.gov (United States)

    Dzieciol, Anna M; Bachevalier, Jocelyne; Saleem, Kadharbatcha S; Gadian, David G; Saunders, Richard; Chong, W K Kling; Banks, Tina; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2017-01-01

    Developmental amnesia (DA) is a selective episodic memory disorder associated with hypoxia-induced bilateral hippocampal atrophy of early onset. Despite the systemic impact of hypoxia-ischaemia, the resulting brain damage was previously reported to be largely limited to the hippocampus. However, the thalamus and the mammillary bodies are parts of the hippocampal-diencephalic network and are therefore also at risk of injury following hypoxic-ischaemic events. Here, we report a neuroimaging investigation of diencephalic damage in a group of 18 patients with DA (age range 11-35 years), and an equal number of controls. Importantly, we uncovered a marked degree of atrophy in the mammillary bodies in two thirds of our patients. In addition, as a group, patients had mildly reduced thalamic volumes. The size of the anterior-mid thalamic (AMT) segment was correlated with patients' visual memory performance. Thus, in addition to the hippocampus, the diencephalic structures also appear to play a role in the patients' memory deficit. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Structural hippocampal network alterations during healthy aging: A multi-modal MRI study

    Directory of Open Access Journals (Sweden)

    Amandine ePelletier

    2013-12-01

    Full Text Available While hippocampal atrophy has been described during healthy aging, few studies have examined its relationship with the integrity of White Matter (WM connecting tracts of the limbic system. This investigation examined WM structural damage specifically related to hippocampal atrophy in healthy aging subjects (n=129, using morphological MRI to assess hippocampal volume and Diffusion Tensor Imaging (DTI to assess WM integrity. Subjects with Mild Cognitive Impairment (MCI or dementia were excluded from the analysis. In our sample, increasing age was significantly associated with reduced hippocampal volume and reduced Fractional Anisotropy (FA at the level of the fornix and the cingulum bundle. The findings also demonstrate that hippocampal atrophy was specifically associated with reduced FA of the fornix bundle, but it was not related to alteration of the cingulum bundle. Our results indicate that the relationship between hippocampal atrophy and fornix FA values is not due to an independent effect of age on both structures. A recursive regression procedure was applied to evaluate sequential relationships between the alterations of these two brain structures. When both hippocampal atrophy and fornix FA values were included in the same model to predict age, fornix FA values remained significant whereas hippocampal atrophy was no longer significantly associated with age. According to this latter finding, hippocampal atrophy in healthy aging could be mediated by a loss of fornix connections. Structural alterations of this part of the limbic system, which have been associated with neurodegeneration in Alzheimer’s disease, result at least in part from the aging process.

  16. Preliminary evidence for obesity and elevations in fasting insulin mediating associations between cortisol awakening response and hippocampal volumes and frontal atrophy.

    Science.gov (United States)

    Ursache, Alexandra; Wedin, William; Tirsi, Aziz; Convit, Antonio

    2012-08-01

    Recent studies have demonstrated alterations in the cortisol awakening response (CAR) and brain abnormalities in adults with obesity and type 2 diabetes mellitus (T2DM). While adolescents with T2DM exhibit similar brain abnormalities, less is known about whether brain impairments and hypothalamic-pituitary-adrenal (HPA) axis abnormalities are already present in adolescents with pre-diabetic conditions such as insulin resistance (IR). This study included 33 adolescents with IR and 20 without IR. Adolescents with IR had a blunted CAR, smaller hippocampal volumes, and greater frontal lobe atrophy compared to controls. Mediation analyses indicated pathways whereby a smaller CAR was associated with higher BMI which was in turn associated with fasting insulin levels, which in turn was related to smaller hippocampal volume and greater frontal lobe atrophy. While we had hypothesized that HPA dysregulation may result from brain abnormalities, our findings suggest that HPA dysregulation may also impact brain structures through associations with metabolic abnormalities. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

    Science.gov (United States)

    Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

    2011-03-01

    Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

  18. Hippocampal sclerosis: correlation of MR imaging findings with surgical outcome

    International Nuclear Information System (INIS)

    Kim, Yoon Hee; Chang, Kee Hyun; Kim, Kyung Won; Han, Moon Hee; Park, Sung Ho; Nam, Hyun Woo; Choi, Kyu Ho; Cho, Woo Ho

    2001-01-01

    Atrophy and a high T2 signal of the hippocampus are known to be the principal MR imaging findings of hippocampal sclerosis. The purpose of this study was to determine whether or not individual MRI findings correlate with surgical outcome in patients with this condition. Preoperative MR imaging findings in 57 consecutive patients with pathologically-proven hippocampal sclerosis who underwent anterior temporal lobectomy and were followed-up for 24 months or more were retrospectively reviewed, and the results were compared with the postsurgical outcome (Engel classification). The MR images included routine sagittal T1-weighted and axial T2-weighted spin-echo images, and oblique coronal T1-weighted 3D gradient-echo and T2-weighted 2D fast spin-echo images obtained on either a 1.5 T or 1.0 T unit. The images were visually evaluated by two neuroradiologists blinded to the outcome; their focus was the presence or absence of atrophy and a high T2 hippocampal signal. Hippocampal atrophy was seen in 96% of cases (55/57) [100% (53/53) of the good outcome group (Engel class I and II), and 50% (2/4) of the poor outcome group (class III and IV)]. A high T2 hippocampal signal was seen in 61% of cases (35/57) [62% (33/53) of the good outcome group and 50% (2/4) of the poor outcome group]. All 35 patients with a high T2 signal had hippocampal atrophy. 'Normal' hippocampus, as revealed by MR imaging, occurred in 4% of patients (2/57), both of whom showed a poor outcome (Engel class III). The presence or absence of hippocampal atrophy correlated well with surgical outcome (p 0.05). Compared with a high T2 hippocampal signal, hippocampal atrophy is more common and correlates better with surgical outcome. For the prediction of this, it thus appears to be the more useful indicator

  19. Better verbal memory in women than men in MCI despite similar levels of hippocampal atrophy.

    Science.gov (United States)

    Sundermann, Erin E; Biegon, Anat; Rubin, Leah H; Lipton, Richard B; Mowrey, Wenzhu; Landau, Susan; Maki, Pauline M

    2016-04-12

    To examine sex differences in the relationship between clinical symptoms related to Alzheimer disease (AD) (verbal memory deficits) and neurodegeneration (hippocampal volume/intracranial volume ratio [HpVR]) across AD stages. The sample included 379 healthy participants, 694 participants with amnestic mild cognitive impairment (aMCI), and 235 participants with AD and dementia from the Alzheimer's Disease Neuroimaging Initiative who completed the Rey Auditory Verbal Learning Test (RAVLT). Cross-sectional analyses were conducted using linear regression to examine the interaction between sex and HpVR on RAVLT across and within diagnostic groups adjusting for age, education, and APOE ε4 status. Across groups, there were significant sex × HpVR interactions for immediate and delayed recall (p better RAVLT performance was independently associated with female sex (immediate, p = 0.04) and larger HpVR (delayed, p = 0.001). Women showed an advantage in verbal memory despite evidence of moderate hippocampal atrophy. This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages. © 2016 American Academy of Neurology.

  20. Hippocampal disconnection in early Alzheimer's disease: a 7 tesla MRI study

    NARCIS (Netherlands)

    Wisse, L.E.; Reijmer, Y.D.; Telgte, A. ter; Kuijf, H.J.; Leemans, A.; Luijten, P.R.; Koek, H.L.; Geerlings, M.I.; Biessels, G.J.

    2015-01-01

    BACKGROUND: In patients with Alzheimer's disease (AD), atrophy of the entorhinal cortex (ERC) and hippocampal formation may induce degeneration of connecting white matter tracts. OBJECTIVE: We examined the association of hippocampal subfield and ERC atrophy at 7 tesla MRI with fornix and

  1. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease.

    Science.gov (United States)

    Borba, Ericksen Mielle; Duarte, Juliana Avila; Bristot, Giovana; Scotton, Ellen; Camozzato, Ana Luiza; Chaves, Márcia Lorena Fagundes

    2016-01-01

    Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

  2. Hippocampal Sclerosis of Aging, a Common Alzheimer's Disease 'Mimic': Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe.

    Science.gov (United States)

    Nho, Kwangsik; Saykin, Andrew J; Nelson, Peter T

    2016-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a common brain disease in older adults with a clinical course that is similar to Alzheimer's disease. Four single-nucleotide polymorphisms (SNPs) have previously shown association with HS-Aging. The present study investigated structural brain changes associated with these SNPs using surface-based analysis. Participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN, TMEM106B, ABCC9, and KCNMB2 (minor allele frequency for each is >30%). A fifth SNP (near the ABCC9 gene) was evaluated in post-hoc analysis. The GRN risk SNP (rs5848_T) was associated with a pattern of atrophy in the dorsomedial frontal lobes bilaterally, remarkable since GRN is a risk factor for frontotemporal dementia. The ABCC9 risk SNP (rs704180_A) was associated with multifocal atrophy whereas a SNP (rs7488080_A) nearby (∼50 kb upstream) ABCC9 was associated with atrophy in the right entorhinal cortex. Neither TMEM106B (rs1990622_T), KCNMB2 (rs9637454_A), nor any of the non-risk alleles were associated with brain atrophy. When all four previously identified HS-Aging risk SNPs were summed into a polygenic risk score, there was a pattern of associated multifocal brain atrophy in a predominately frontal pattern. We conclude that common SNPs previously linked to HS-Aging pathology were associated with a distinct pattern of anterior cortical atrophy. Genetic variation associated with HS-Aging pathology may represent a non-Alzheimer's disease contribution to atrophy outside of the hippocampus in older adults.

  3. Hepatic parenchymal atrophy induction for intractable segmental bile duct injury after liver resection.

    Science.gov (United States)

    Hwang, Shin; Park, Gil-Chun; Ha, Tae-Yong; Ko, Gi-Young; Gwon, Dong-Il; Choi, Young-Il; Song, Gi-Won; Lee, Sung-Gyu

    2012-05-01

    Liver resection can result in various types of bile duct injuries but their treatment is usually difficult and often leads to intractable clinical course. We present an unusual case of hepatic segment III duct (B3) injury, which occurred after left medial sectionectomy for large hepatocellular carcinoma and was incidentally detected 1 week later due to bile leak. Since the pattern of this B3 injury was not adequate for operative biliary reconstruction, atrophy induction of the involved hepatic parenchyma was attempted. This treatment consisted of embolization of the segment III portal branch to inhibit bile production, induction of heavy adhesion at the bile leak site and clamping of the percutaneous transhepatic biliary drainage (PTBD) tube to accelerate segment III atrophy. This entire procedure, from liver resection to PTBD tube removal took 4 months. This patient has shown no other complication or tumor recurrence for 4 years to date. These findings suggest that percutaneous segmental portal vein embolization, followed by intentional clamping of external biliary drainage, can effectively control intractable bile leak from segmental bile duct injury.

  4. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Ericksen Mielle Borba

    2016-12-01

    Full Text Available Background/Aims: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD pathology. Serum brain-derived neurotrophic factor (BDNF reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]. Methods: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. Results: MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. Discussion: The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

  5. Mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury by improving lysosomal function and autophagic flux.

    Science.gov (United States)

    Zhou, Tianen; Liang, Lian; Liang, Yanran; Yu, Tao; Zeng, Chaotao; Jiang, Longyuan

    2017-09-15

    Mild hypothermia has been proven to be useful to treat brain ischemia/reperfusion injury. However, the underlying mechanisms have not yet been fully elucidated. The present study was undertaken to determine whether mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion(OGD/R)-induced injury via improving lysosomal function and autophagic flux. The results showed that OGD/R induced the occurrence of autophagy, while the acidic environment inside the lysosomes was altered. The autophagic flux assay with RFP-GFP tf-LC3 was impeded in hippocampal neurons after OGD/R. Mild hypothermia recovered the lysosomal acidic fluorescence and the lysosomal marker protein expression of LAMP2, which decreased after OGD/R.Furthermore, we found that mild hypothermia up-regulated autophagic flux and promoted the fusion of autophagosomes and lysosomes in hippocampal neurons following OGD/R injury, but could be reversed by treatment with chloroquine, which acts as a lysosome inhibitor. We also found that mild hypothermia improved mitochondrial autophagy in hippocampal neurons following OGD/R injury. Finally,we found that chloroquine blocked the protective effects of mild hypothermia against OGD/R-induced cell death and injury. Taken together, the present study indicates that mild hypothermia protects hippocampal neurons against OGD/R-induced injury by improving lysosomal function and autophagic flux. Copyright © 2017. Published by Elsevier Inc.

  6. Relation between hippocampal damage and cerebral cortical function in Alzheimer's disease

    International Nuclear Information System (INIS)

    Hanyu, Haruo; Asano, Tetsuichi; Kogure, Daiji; Sakurai, Hirofumi; Iwamoto, Toshihiko; Takasaki, Masaru

    2000-01-01

    We investigated the relation between hippocampal damage and cerebral cortical dysfunction in Alzheimer's disease (AD) using MRI and SPECT. Nineteen patients with AD and 10 control subjects were studied. Hippocampal damage (including hippocampal formation, entorhinal cortex, and parahippocampal white matter) was assessed to evaluate the severity of atrophy and the magnetization transfer ratio (MTR) and cerebral cortical dysfunction was evaluated by quantitative cerebral blood flow (CBF) measurements using SPECT with 99mTc-ECD. Compared with controls, patients with AD had significantly more atrophy of the medial temporal lobe and a decrease in MTRs of the hippocampus and parahippocampus. There were significant correlations between the severity of hippocampal damage and regional CBF in temporoparietal lobes. Mini-Mental State Examination scores significantly correlated with the severity of hippocampal damage and regional CBFs in temporoparietal lobes. These results suggest that the functional effect of hippocampal damage occurs in temporoparietal lobes in AD, probably due to neuronal disconnections between hippocampal areas (including the entorhinal cortex) and temporoparietal lobes. (author)

  7. Apoptosis-inducing effect of selective sensory or motor nerve injury on skeletal muscle atrophy

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    Lei ZHAO

    2011-09-01

    Full Text Available Objective To explore the apoptosis-inducing effect of selective sensory or motor nerve injury on skeletal muscle atrophy.Methods Thirty healthy adult SD rats were randomly divided into three groups,namely,ventral root transection group(VRT group,received left L4-L6 ventral rhizotomy,dorsal root transection group(DRT group,received left L4-L6 dorsal rhizotomy,and sciatic nerve transection group(SNT group,received left sciatic nerve transection.Each group comprised 10 SD rats.The bilateral gastrocnemius was harvested 10 weeks after operation to observe the apoptosis and Fas/FasL expression of the skeletal muscle cells through fluorescent labeling,transmission electron microscopy,and immunohistochemistry.Result Ten weeks after the denervation,apoptosis-related changes,especially obvious changes of the nuclear apoptotic morphology,were observed in the skeletal muscle cells.The aggregation degree of the nucleus and the expression of Fas/FasL increased in the following order: DRT group,VRT group,and SNT group.No apoptotic body,but early apoptotic morphology,was found in the denervated gastrocnemius through transmission electron microscopy.Conclusions The effect of motor nerve injury on skeletal muscle atrophy is more serious than that of sensory nerve injury.The rebuilding of motor nerves should be preferentially considered in the clinical treatment of muscle atrophy induced by denervation.

  8. Preventive effect of piracetam and vinpocetine on hypoxia-reoxygenation induced injury in primary hippocampal culture.

    Science.gov (United States)

    Solanki, P; Prasad, D; Muthuraju, S; Sharma, A K; Singh, S B; Ilavzhagan, G

    2011-04-01

    The present study investigates the potential of Piracetam and Vinpocetine (nootropic drugs, known to possess neuroprotective properties) in preventing hypoxia-reoxygenation induced oxidative stress in primary hippocampal cell culture. The hippocampal culture was exposed to hypoxia (95% N(2), 5% CO(2)) for 3h and followed by 1h of reoxygenation (21% O(2) and 5% CO(2)) at 37 °C. The primary hippocampal cultures were supplemented with the optimum dose of Piracetam and Vinpocetine, independently, and the cultures were divided into six groups, viz. Control/Normoxia, Hypoxia, Hypoxia+Piracetam, Hypoxia+Vinpocetine, Normoxia + Piracetam and Normoxia+Vinpocetine. The cell-viability assays and biochemical oxidative stress parameters were evaluated for each of the six groups. Administration of 1mM Piracetam or 500 nM Vinpocetine significantly prevents the culture from hypoxia-reoxygenation injury when determined by Neutral Red assay, LDH release and Acetylcholine esterase activity. Results showed that Piracetam and Vinpocetine supplementation significantly prevented the fall of mitochondrial membrane potential, rise in ROS generation and reduction in antioxidant levels associated with the hypoxia-reoxygenation injury. In conclusion, the present study establishes that both Piracetam and Vinpocetine give neuroprotection against hypoxia-reoxygenation injury in primary hippocampal cell culture. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia.

    Science.gov (United States)

    La Joie, Renaud; Perrotin, Audrey; de La Sayette, Vincent; Egret, Stéphanie; Doeuvre, Loïc; Belliard, Serge; Eustache, Francis; Desgranges, Béatrice; Chételat, Gaël

    2013-01-01

    Hippocampal atrophy is a well-known feature of Alzheimer's disease (AD), but sensitivity and specificity of hippocampal volumetry are limited. Neuropathological studies have shown that hippocampal subfields are differentially vulnerable to AD; hippocampal subfield volumetry may thus prove to be more accurate than global hippocampal volumetry to detect AD. CA1, subiculum and other subfields were manually delineated from 40 healthy controls, 18 AD, 17 amnestic Mild Cognitive Impairment (aMCI), and 8 semantic dementia (SD) patients using a previously developed high resolution MRI procedure. Non-parametric group comparisons and receiver operating characteristic (ROC) analyses were conducted. Complementary analyses were conducted to evaluate differences of hemispheric asymmetry and anterior-predominance between AD and SD patients and to distinguish aMCI patients with or without β-amyloid deposition as assessed by Florbetapir-TEP. Global hippocampi were atrophied in all three patient groups and volume decreases were maximal in the CA1 subfield (22% loss in aMCI, 27% in both AD and SD; all p volumetry was more accurate than global hippocampal measurement to distinguish patients from controls (areas under the ROC curve = 0.88 and 0.76, respectively; p = 0.05) and preliminary analyses suggest that it was independent from the presence of β-amyloid deposition. In patients with SD, whereas the degree of CA1 and subiculum atrophy was similar to that found in AD patients, hemispheric and anterior-posterior asymmetry were significantly more marked than in AD with greater involvement of the left and anterior hippocampal subfields. The findings suggest that CA1 measurement is more sensitive than global hippocampal volumetry to detect structural changes at the pre-dementia stage, although the predominance of CA1 atrophy does not appear to be specific to AD pathophysiological processes.

  10. Autopsy-confirmed hippocampal-sparing Alzheimer's disease with delusional jealousy as initial manifestation.

    Science.gov (United States)

    Fujishiro, Hiroshige; Iritani, Shuji; Hattori, Miho; Sekiguchi, Hirotaka; Matsunaga, Shinji; Habuchi, Chikako; Torii, Youta; Umeda, Kentaro; Ozaki, Norio; Yoshida, Mari; Fujita, Kiyoshi

    2015-09-01

    Alzheimer's disease (AD) is clinically characterized by gradual onset over years with worsening of cognition. The initial and most prominent cognitive deficit is commonly memory dysfunction. However, a subset of AD cases has less hippocampal atrophy than would be expected relative to the predominance of cortical atrophy. These hippocampal-sparing cases have distinctive clinical features, including the presence of focal cortical clinical syndromes. Given that previous studies have indicated that severe hippocampal atrophy corresponds to prominent loss of episodic memory, it is likely that memory impairment is initially absent in hippocampal-sparing AD cases. Here, we report on a patient with an 8-year history of delusional jealousy with insidious onset who was clinically diagnosed as possible AD and pathologically confirmed to have AD with relatively preserved neurons in the hippocampus. This patient had delusional jealousy with a long pre-dementia stage, which initially was characterized by lack of memory impairment. Head magnetic resonance imaging findings showed preserved hippocampal volume with bilateral enlarged ventricles and mild-to-moderate cortical atrophy. Head single-photon emission computed tomography revealed severely decreased regional cerebral blood flow in the right temporal lobe. The resolution of the delusion was attributed to pharmacotherapy by an acetylcholinesterase inhibitor, suggesting that the occurrence of delusional jealousy was due to the disease process of AD. Although the neural basis of delusional jealousy remains unclear, this hippocampal-sparing AD case may be classified as an atypical presentation of AD. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

  11. Comparison between visual assessment of MTA and hippocampal volumes in an elderly, non-demented population

    International Nuclear Information System (INIS)

    Cavallin, Lena; Axelsson, Rimma; Bronge, Lena; Zhang, Yi; Oeksengaard, Anne-Rita; Wahlund, Lars-Olof; Fratiglioni, Laura

    2012-01-01

    Background: It is important to have a replicable easy method for monitoring atrophy progression in Alzheimer's disease. Volumetric methods for calculating hippocampal volume are time-consuming and commonly used in research. Visual assessments of medial temporal lobe atrophy (vaMTA) is a rapid method for clinical use. This method has not been tested in a large non-demented population in comparison with volumetry measurements. Since hippocampal volume decreases with time even in normal aging there is also a need to study the normal age differences of medial temporal lobe atrophy. Purpose: To compare visual assessment of medial temporal lobe atrophy (vaMTA) with hippocampal volume in a healthy, non-demented elderly population. To describe normal ageing using vaMTA. Material and Methods: Non-demented individuals aged 60, 66, 72, 78, 81, 84, and ≥87 years old were recruited from the Swedish National study on Ageing and Care in Kungsholmen (SNAC-K), Sweden. Standard magnetic resonance imaging (MRI) scans, vaMTA, and calculations of hippocampal volumes were performed in 544 subjects. Results: Significant correlation (rs = -0.32, P 80-year-old individuals

  12. Ipsilateral hippocampal atrophy is associated with long-term memory dysfunction after ischemic stroke in young adults.

    Science.gov (United States)

    Schaapsmeerders, Pauline; van Uden, Inge W M; Tuladhar, Anil M; Maaijwee, Noortje A M; van Dijk, Ewoud J; Rutten-Jacobs, Loes C A; Arntz, Renate M; Schoonderwaldt, Hennie C; Dorresteijn, Lucille D A; de Leeuw, Frank-Erik; Kessels, Roy P C

    2015-07-01

    Memory impairment after stroke in young adults is poorly understood. In elderly stroke survivors memory impairments and the concomitant loss of hippocampal volume are usually explained by coexisting neurodegenerative disease (e.g., amyloid pathology) in interaction with stroke. However, neurodegenerative disease, such as amyloid pathology, is generally absent at young age. Accumulating evidence suggests that infarction itself may cause secondary neurodegeneration in remote areas. Therefore, we investigated the relation between long-term memory performance and hippocampal volume in young patients with first-ever ischemic stroke. We studied all consecutive first-ever ischemic stroke patients, aged 18-50 years, admitted to our academic hospital center between 1980 and 2010. Episodic memory of 173 patients was assessed using the Rey Auditory Verbal Learning Test and the Rey Complex Figure and compared with 87 stroke-free controls. Hippocampal volume was determined using FSL-FIRST, with manual correction. On average 10 years after stroke, patients had smaller ipsilateral hippocampal volumes compared with controls after left-hemispheric stroke (5.4%) and right-hemispheric stroke (7.7%), with most apparent memory dysfunctioning after left-hemispheric stroke. A larger hemispheric stroke was associated with a smaller ipsilateral hippocampal volume (b=-0.003, Pstroke (b=-0.028 ml, P=0.002) and right-hemispheric stroke (b=-0.015 ml, P=0.03). Our results suggest that infarction is associated with remote injury to the hippocampus, which may lower or expedite the threshold for cognitive impairment or even dementia later in life. © 2015 Wiley Periodicals, Inc.

  13. Impairment on a self-ordered working memory task in patients with early-acquired hippocampal atrophy.

    Science.gov (United States)

    Geva, Sharon; Cooper, Janine M; Gadian, David G; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2016-08-01

    One of the features of both adult-onset and developmental forms of amnesia resulting from bilateral medial temporal lobe damage, or even from relatively selective damage to the hippocampus, is the sparing of working memory. Recently, however, a number of studies have reported deficits on working memory tasks in patients with damage to the hippocampus and in macaque monkeys with neonatal hippocampal lesions. These studies suggest that successful performance on working memory tasks with high memory load require the contribution of the hippocampus. Here we compared performance on a working memory task (the Self-ordered Pointing Task), between patients with early onset hippocampal damage and a group of healthy controls. Consistent with the findings in the monkeys with neonatal lesions, we found that the patients were impaired on the task, but only on blocks of trials with intermediate memory load. Importantly, only intermediate to high memory load blocks yielded significant correlations between task performance and hippocampal volume. Additionally, we found no evidence of proactive interference in either group, and no evidence of an effect of time since injury on performance. We discuss the role of the hippocampus and its interactions with the prefrontal cortex in serving working memory. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Impairment on a self-ordered working memory task in patients with early-acquired hippocampal atrophy

    Directory of Open Access Journals (Sweden)

    Sharon Geva

    2016-08-01

    Full Text Available One of the features of both adult-onset and developmental forms of amnesia resulting from bilateral medial temporal lobe damage, or even from relatively selective damage to the hippocampus, is the sparing of working memory. Recently, however, a number of studies have reported deficits on working memory tasks in patients with damage to the hippocampus and in macaque monkeys with neonatal hippocampal lesions. These studies suggest that successful performance on working memory tasks with high memory load require the contribution of the hippocampus. Here we compared performance on a working memory task (the Self-ordered Pointing Task, between patients with early onset hippocampal damage and a group of healthy controls. Consistent with the findings in the monkeys with neonatal lesions, we found that the patients were impaired on the task, but only on blocks of trials with intermediate memory load. Importantly, only intermediate to high memory load blocks yielded significant correlations between task performance and hippocampal volume. Additionally, we found no evidence of proactive interference in either group, and no evidence of an effect of time since injury on performance. We discuss the role of the hippocampus and its interactions with the prefrontal cortex in serving working memory.

  15. Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice.

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    Sindhu K Madathil

    Full Text Available Traumatic brain injury (TBI survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1, a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal overexpression of IGF-1 using the controlled cortical impact (CCI injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI.

  16. Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice

    Science.gov (United States)

    Madathil, Sindhu K.; Carlson, Shaun W.; Brelsfoard, Jennifer M.; Ye, Ping; D’Ercole, A. Joseph; Saatman, Kathryn E.

    2013-01-01

    Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI. PMID:23826235

  17. Cube propagation for focal brain atrophy estimation

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru; Sørensen, Lauge; Darkner, Sune

    2013-01-01

    Precise and robust whole brain, ventricle, and hippocampal atrophy measurements are important as they serve as biomarkers for Alzheimer’s disease. They are used as secondary outcomes in drug trials, and they correlate with the cognitive scores. When two successive scans are non-linearly aligned...

  18. Hippocampal volume measurement in patients with Meniere's disease : a pilot study

    NARCIS (Netherlands)

    van Cruijsen, Nynke; Hiemstra, Wilma M.; Meiners, Linda C.; Wit, Hero P.; Albers, Frans W. J.

    2007-01-01

    Conclusion. No signs of chronic stress as in hippocampal atrophy were present in patients with Meniere's disease. Objective. To evaluate the effect of chronic stress (allostatic load) by measuring hippocampal volume in patients with Meniere's disease. Subjects and methods. Ten patients with

  19. Apolipoprotein E genotype is associated with temporal and hippocampal atrophy rates in healthy elderly adults: a tensor-based morphometry study.

    Science.gov (United States)

    Lu, Po H; Thompson, Paul M; Leow, Alex; Lee, Grace J; Lee, Agatha; Yanovsky, Igor; Parikshak, Neelroop; Khoo, Theresa; Wu, Stephanie; Geschwind, Daniel; Bartzokis, George

    2011-01-01

    Apolipoprotein E (ApoE) ε4 genotype is a strong risk factor for developing Alzheimer's disease (AD). Conversely, the presence of the ε2 allele has been shown to mitigate cognitive decline. Tensor-based morphometry (TBM), a novel computational approach for visualizing longitudinal progression of brain atrophy, was used to determine whether cognitively intact elderly participants with the ε4 allele demonstrate greater volume reduction than those with the ε2 allele. Healthy "younger elderly" volunteers, aged 55-75, were recruited from the community and hospital staff. They were evaluated with a baseline and follow-up MRI scan (mean scan interval = 4.72 years, s.d. = 0.55) and completed ApoE genotyping. Twenty-seven participants were included in the study of which 16 had the ε4 allele (all heterozygous ε3ε4 genotype) and 11 had the ε2ε3 genotype. The two groups did not differ significantly on any demographic characteristics and all subjects were cognitively "normal" at both baseline and follow-up time points. TBM was used to create 3D maps of local brain tissue atrophy rates for individual participants; these spatially detailed 3D maps were compared between the two ApoE groups. Regional analyses were performed and the ε4 group demonstrated significantly greater annual atrophy rates in the temporal lobes (p = 0.048) and hippocampus (p = 0.016); greater volume loss was observed in the right hippocampus than the left. TBM appears to be useful in tracking longitudinal progression of brain atrophy in cognitively asymptomatic adults. Possession of the ε4 allele is associated with greater temporal and hippocampal volume reduction well before the onset of cognitive deficits.

  20. Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials.

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    K Abigail Andrews

    Full Text Available There is considerable interest in designing therapeutic studies of individuals at risk of Alzheimer disease (AD to prevent the onset of symptoms. Cortical β-amyloid plaques, the first stage of AD pathology, can be detected in vivo using positron emission tomography (PET, and several studies have shown that ~1/3 of healthy elderly have significant β-amyloid deposition. Here we assessed whether asymptomatic amyloid-PET-positive controls have increased rates of brain atrophy, which could be harnessed as an outcome measure for AD prevention trials. We assessed 66 control subjects (age = 73.5±7.3 yrs; MMSE = 29±1.3 from the Australian Imaging Biomarkers & Lifestyle study who had a baseline Pittsburgh Compound B (PiB PET scan and two 3T MRI scans ~18-months apart. We calculated PET standard uptake value ratios (SUVR, and classified individuals as amyloid-positive/negative. Baseline and 18-month MRI scans were registered, and brain, hippocampal, and ventricular volumes and annualized volume changes calculated. Increasing baseline PiB-PET measures of β-amyloid load correlated with hippocampal atrophy rate independent of age (p = 0.014. Twenty-two (1/3 were PiB-positive (SUVR>1.40, the remaining 44 PiB-negative (SUVR≤1.31. Compared to PiB-negatives, PiB-positive individuals were older (76.8±7.5 vs. 71.7±7.5, p<0.05 and more were APOE4 positive (63.6% vs. 19.2%, p<0.01 but there were no differences in baseline brain, ventricle or hippocampal volumes, either with or without correction for total intracranial volume, once age and gender were accounted for. The PiB-positive group had greater total hippocampal loss (0.06±0.08 vs. 0.02±0.05 ml/yr, p = 0.02, independent of age and gender, with non-significantly higher rates of whole brain (7.1±9.4 vs. 4.7±5.5 ml/yr and ventricular (2.0±3.0 vs. 1.1±1.0 ml/yr change. Based on the observed effect size, recruiting 384 (95%CI 195-1080 amyloid-positive subjects/arm will provide 80% power to detect 25

  1. A mathematical model of aging-related and cortisol induced hippocampal dysfunction

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    Jones Janette JL

    2009-03-01

    Full Text Available Abstract Background The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD, the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML. We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated. Results The in silicoSBML model reflected the in vivoaging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA, increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation. Conclusion Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitroand in vivostudies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people.

  2. Electroencephalography reveals lower regional blood perfusion and atrophy of the temporoparietal network associated with memory deficits and hippocampal volume reduction in mild cognitive impairment due to Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Moretti DV

    2015-02-01

    Full Text Available Davide Vito MorettiNational Institute for the research and cure of Alzheimer’s disease, S. John of God, Fatebenefratelli, Brescia, Italy Background: An increased electroencephalographic (EEG upper/lower alpha power ratio has been associated with less regional blood perfusion, atrophy of the temporoparietal region of the brain, and reduction of hippocampal volume in subjects affected by mild cognitive impairment due to Alzheimer’s disease as compared with subjects who do not develop the disease. Moreover, EEG theta frequency activity is quite different in these groups. This study investigated the correlation between biomarkers and memory performance.Methods: EEG α3/α2 power ratio and cortical thickness were computed in 74 adult subjects with prodromal Alzheimer’s disease. Twenty of these subjects also underwent assessment of blood perfusion by single-photon emission computed tomography (SPECT. Pearson’s r was used to assess the correlation between cortical thinning, brain perfusion, and memory impairment.Results: In the higher α3/α2 frequency power ratio group, greater cortical atrophy and lower regional perfusion in the temporoparietal cortex was correlated with an increase in EEG theta frequency. Memory impairment was more pronounced in the magnetic resonance imaging group and SPECT groups.Conclusion: A high EEG upper/low alpha power ratio was associated with cortical thinning and less perfusion in the temporoparietal area. Moreover, atrophy and less regional perfusion were significantly correlated with memory impairment in subjects with prodromal Alzheimer’s disease. The EEG upper/lower alpha frequency power ratio could be useful for identifying individuals at risk for progression to Alzheimer’s dementia and may be of value in the clinical context.Keywords: electroencephalography, perfusion, atrophy, temporoparietal network, memory deficits, hippocampal volume, mild cognitive impairment, Alzheimer’s disease

  3. Moderate traumatic brain injury causes acute dendritic and synaptic degeneration in the hippocampal dentate gyrus.

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    Xiang Gao

    Full Text Available Hippocampal injury-associated learning and memory deficits are frequent hallmarks of brain trauma and are the most enduring and devastating consequences following traumatic brain injury (TBI. Several reports, including our recent paper, showed that TBI brought on by a moderate level of controlled cortical impact (CCI induces immature newborn neuron death in the hippocampal dentate gyrus. In contrast, the majority of mature neurons are spared. Less research has been focused on these spared neurons, which may also be injured or compromised by TBI. Here we examined the dendrite morphologies, dendritic spines, and synaptic structures using a genetic approach in combination with immunohistochemistry and Golgi staining. We found that although most of the mature granular neurons were spared following TBI at a moderate level of impact, they exhibited dramatic dendritic beading and fragmentation, decreased number of dendritic branches, and a lower density of dendritic spines, particularly the mushroom-shaped mature spines. Further studies showed that the density of synapses in the molecular layer of the hippocampal dentate gyrus was significantly reduced. The electrophysiological activity of neurons was impaired as well. These results indicate that TBI not only induces cell death in immature granular neurons, it also causes significant dendritic and synaptic degeneration in pathohistology. TBI also impairs the function of the spared mature granular neurons in the hippocampal dentate gyrus. These observations point to a potential anatomic substrate to explain, in part, the development of posttraumatic memory deficits. They also indicate that dendritic damage in the hippocampal dentate gyrus may serve as a therapeutic target following TBI.

  4. Calpain 3 Expression Pattern during Gastrocnemius Muscle Atrophy and Regeneration Following Sciatic Nerve Injury in Rats

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    Ronghua Wu

    2015-11-01

    Full Text Available Calpain 3 (CAPN3, also known as p94, is a skeletal muscle-specific member of the calpain family that is involved in muscular dystrophy; however, the roles of CAPN3 in muscular atrophy and regeneration are yet to be understood. In the present study, we attempted to explain the effect of CAPN3 in muscle atrophy by evaluating CAPN3 expression in rat gastrocnemius muscle following reversible sciatic nerve injury. After nerve injury, the wet weight ratio and cross sectional area (CSA of gastrocnemius muscle were decreased gradually from 1–14 days and then recovery from 14–28 days. The active form of CAPN3 (~62 kDa protein decreased slightly on day 3 and then increased from day 7 to 14 before a decrease from day 14 to 28. The result of linear correlation analysis showed that expression of the active CAPN3 protein level was negatively correlated with muscle wet weight ratio. CAPN3 knockdown by short interfering RNA (siRNA injection improved muscle recovery on days 7 and 14 after injury as compared to that observed with control siRNA treatment. Depletion of CAPN3 gene expression could promote myoblast differentiation in L6 cells. Based on these findings, we conclude that the expression pattern of the active CAPN3 protein is linked to muscle atrophy and regeneration following denervation: its upregulation during early stages may promote satellite cell renewal by inhibiting differentiation, whereas in later stages, CAPN3 expression may be downregulated to stimulate myogenic differentiation and enhance recovery. These results provide a novel mechanistic insight into the role of CAPN3 protein in muscle regeneration after peripheral nerve injury.

  5. Comparison between visual assessment of MTA and hippocampal volumes in an elderly, non-demented population

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    Cavallin, Lena; Axelsson, Rimma [CLINTEC, Div. of Medical Imaging and Technology, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Dept. of Radiology, Karolinska Univ. Hospital, Stockholm (Sweden)], e-mail: lena.cavallin@karolinska.se; Bronge, Lena [CLINTEC, Div. of Medical Imaging and Technology, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Aleris Diagnostics, Stockholm (Sweden); Zhang, Yi [NVS, Novum, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Oeksengaard, Anne-Rita [NVS, Novum, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Ulleval Univ. Hospital and Asker and Baerum Hospital, Oslo (Norway); Wahlund, Lars-Olof [NVS, Novum, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Swedish Brain Power, Karolinska Univ. Hospital, Stockholm (Sweden); Fratiglioni, Laura [ARC Karolinska Inst. Stockholm (Sweden)

    2012-06-15

    Background: It is important to have a replicable easy method for monitoring atrophy progression in Alzheimer's disease. Volumetric methods for calculating hippocampal volume are time-consuming and commonly used in research. Visual assessments of medial temporal lobe atrophy (vaMTA) is a rapid method for clinical use. This method has not been tested in a large non-demented population in comparison with volumetry measurements. Since hippocampal volume decreases with time even in normal aging there is also a need to study the normal age differences of medial temporal lobe atrophy. Purpose: To compare visual assessment of medial temporal lobe atrophy (vaMTA) with hippocampal volume in a healthy, non-demented elderly population. To describe normal ageing using vaMTA. Material and Methods: Non-demented individuals aged 60, 66, 72, 78, 81, 84, and {>=}87 years old were recruited from the Swedish National study on Ageing and Care in Kungsholmen (SNAC-K), Sweden. Standard magnetic resonance imaging (MRI) scans, vaMTA, and calculations of hippocampal volumes were performed in 544 subjects. Results: Significant correlation (rs = -0.32, P < 0.001, sin; and rs = -0.26, P < 0.001, dx) was found between hippocampal volume measurements and vaMTA. In normal ageing, almost 95% of {<=}66-year-olds had a medial temporal lobe atrophy (MTA) score {<=}1, with possible scores ranging from 0 to 4. Subjects aged 72, 78, and 81 years scored {<=}2, while the two oldest age groups had scores {<=}3. Conclusion: There was a highly significant correlation between volumetric measurements of the hippocampus and MTA scoring. In normal ageing, there is increasing MTA score. For non-demented elderly individuals {<=}70 years, an MTA score of 0-1 may be considered normal, compared with MTA {<=}2 for 70-80-years and MTA 3 for >80-year-old individuals.

  6. Associations between hippocampal morphometry and neuropathologic markers of Alzheimer's disease using 7 T MRI

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    Anna E. Blanken

    2017-01-01

    Full Text Available Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD and 7 cognitively normal (NC subjects. Brains were scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial distances using automated segmentation techniques. Hippocampal slices were stained for amyloid beta (Aβ, tau, and cresyl violet to evaluate neuronal counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were manually traced so that the neuronal counts, Aβ, and tau burden could be obtained for each region. We used linear regression to detect associations between hippocampal atrophy in 3D, clinical diagnosis and total as well as subfield pathology burden measures. As expected, we found significant correlations between hippocampal radial distance and mean neuronal count, as well as diagnosis. There were subfield specific associations between hippocampal radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and subiculum. These results provide further validation for the European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP.

  7. Temporal lobe developmental malformations and epilepsy: dual pathology and bilateral hippocampal abnormalities.

    Science.gov (United States)

    Ho, S S; Kuzniecky, R I; Gilliam, F; Faught, E; Morawetz, R

    1998-03-01

    Temporal lobe developmental malformations (TLDM) with focal cortical dysplasia and balloon cells may coexist with mesial temporal sclerosis. The true incidence of this dual pathology is unknown. Our aim was to assess the frequency of amygdala (AM)-hippocampal abnormality in a homogeneous population with this specific developmental malformation. MRI-based volumetry of the AM and hippocampal formation (HF) in 30 patients with unilateral TLDM and intractable partial epilepsy was performed. A volume normalization process defined a normal range of HF and AM volumes in control subjects, and enabled the detection of bilateral volume loss. Normalized volumes detected HF atrophy in 26 patients (nine unilateral and 17 bilateral) and AM atrophy in 18 patients (three unilateral and 15 bilateral). Visual analysis detected unilateral HF abnormality in 21 patients and bilateral abnormality in two. When compared with a group of patients with temporal lobe epilepsy and pure hippocampal sclerosis (N = 92), where volumetry revealed bilateral HF atrophy in 18%, a significant difference in the frequency of bilateral HF atrophy was found (p Dual pathology is frequent in patients with TLDM (87%), and the AM-HF abnormality is often bilateral (57%). Our data suggest that more widespread and potentially epileptogenic lesions coexist with visibly detectable unilateral TLDM. This has implications for the selection of patients for temporal lobe surgery and may influence surgical strategies.

  8. Homocysteine and brain atrophy on MRI of non-demented elderly

    NARCIS (Netherlands)

    den Heijer, T; Vermeer, SE; Clarke, R; Oudkerk, M; Koudstaal, PJ; Hofman, A; Breteler, MMB

    Patients with Alzheimer's disease have higher plasma homocysteine levels than controls, but it is uncertain whether higher plasma homocysteine levels are involved in the early pathogenesis of the disease. Hippocampal, amygdalar and global brain atrophy on brain MRI have been proposed as early

  9. Hippocampal atrophy on MRI is predictive of histopathological patterns and surgical prognosis in mesial temporal lobe epilepsy with hippocampal sclerosis.

    Science.gov (United States)

    Jardim, Anaclara Prada; Corso, Jeana Torres; Garcia, Maria Teresa Fernandes Castilho; Gaça, Larissa Botelho; Comper, Sandra Mara; Lancellotti, Carmen Lúcia Penteado; Centeno, Ricardo Silva; Carrete, Henrique; Cavalheiro, Esper Abrão; Scorza, Carla Alessandra; Yacubian, Elza Márcia Targas

    2016-12-01

    To correlate hippocampal volumes obtained from brain structural imaging with histopathological patterns of hippocampal sclerosis (HS), in order to predict surgical outcome. Patients with mesial temporal lobe epilepsy (MTLE) with HS were selected. Clinical data were assessed pre-operatively and surgical outcome in the first year post surgery. One block of mid hippocampal body was selected for HS classification according to ILAE criteria. NeuN-immunoreactive cell bodies were counted within hippocampal subfields, in four randomly visual fields, and cell densities were transformed into z-score values. FreeSurfer processing of 1.5T brain structural images was used for subcortical and cortical volumetric estimation of the ipsilateral hippocampus. Univariate analysis of variance and Pearson's correlation test were applied for statistical analyses. Sixty-two cases (31 female, 32 right HS) were included. ILAE type 1 HS was identified in 48 patients, type 2 in eight, type 3 in two, and four had no-HS. Better results regarding seizure control, i.e. ILAE 1, were achieved by patients with type 1 HS (58.3%). Patients with types 1 and 2 had smaller hippocampal volumes compared to those with no-HS (p<0.001 and p=0.004, respectively). Positive correlation was encountered between hippocampal volumes and CA1, CA3, CA4, and total estimated neuronal densities. CA2 was the only sector which did not correlate its neuronal density with hippocampal volume (p=0.390). This is the first study correlating hippocampal volume on MRI submitted to FreeSurfer processing with ILAE patterns of HS and neuronal loss within each hippocampal subfield, a fundamental finding to anticipate surgical prognosis for patients with drug-resistant MTLE and HS. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Abnormalities of hippocampal signal intensity in patients with familial mesial temporal lobe epilepsy

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    Coan A.C.

    2004-01-01

    Full Text Available Mesial temporal lobe epilepsy (MTLE is associated with hippocampal atrophy and hippocampal signal abnormalities. In our series of familial MTLE (FMTLE, we found a high proportion of hippocampal abnormalities. To quantify signal abnormalities in patients with FMTLE we studied 152 individuals (46 of them asymptomatic with FMTLE. We used NIH-Image® for volumetry and signal quantification in coronal T1 inversion recovery and T2 for all cross-sections of the hippocampus. Values diverging by 2 or more SD from the control mean were considered abnormal. T2 hippocampal signal abnormalities were found in 52% of all individuals: 54% of affected subjects and 48% of asymptomatic subjects. T1 hippocampal signal changes were found in 34% of all individuals: 42.5% of affected subjects and 15% of asymptomatic subjects. Analysis of the hippocampal head (first three slices revealed T2 abnormalities in 73% of all individuals (74% of affected subjects and 72% of asymptomatic subjects and T1 abnormalities in 59% (67% of affected subjects and 41% of asymptomatic subjects. Affected individuals had smaller volumes than controls (P < 0.0001. There was no difference in hippocampal volumes between asymptomatic subjects and controls, although 39% of asymptomatic patients had hippocampal atrophy. Patients with an abnormal hippocampal signal (133 individuals had smaller ipsilateral volume, but no linear correlation could be determined. Hippocampal signal abnormalities in FMTLE were more frequently found in the hippocampal head in both affected and asymptomatic family members, including those with normal volumes. These results indicate that subtle abnormalities leading to an abnormal hippocampal signal in FMTLE are not necessarily related to seizures and may be determined by genetic factors.

  11. FRACTIONAL ANISOTROPY OF THE FORNIX AND HIPPOCAMPAL ATROPHY IN ALZHEIMER’S DISEASE

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    Kejal eKantarci

    2014-11-01

    Full Text Available Decrease in the directionality of water diffusion measured with fractional anisotropy on diffusion tensor imaging has been linked to loss of myelin and axons in the white matter. Fornix fractional anisotropy is consistently decreased in patients with mild cognitive impairment and Alzheimer’s disease. Furthermore, decreased fornix fractional anisotropy is one of the earliest MRI abnormalities observed in cognitively normal individuals who are at an increased risk for Alzheimer’s disease, such as in pre-symptomatic carriers of familial Alzheimer’s disease mutations and in pre-clinical Alzheimer’s disease. Reductions of fractional anisotropy at these early stages which predicted the decline in memory function. Fornix carries the efferent projections from the CA1 and CA3 pyramidal neurons of the hippocampus and subiculum, connecting these structures to the septal nuclei, anterior thalamic nucleus, mammillary bodies and medial hypothalamus. Fornix also carries the afferent cholinergic and GABAergic projections from the medial septal nuclei and the adjacent diagonal band back to the medial temporal lobe, interconnecting the core limbic structures. Because fornix carries the axons projecting from the hippocampus, integrity of the fornix is in-part linked to the integrity of the hippocampus. In keeping with that, fornix fractional anisotropy is reduced in subjects with hippocampal atrophy, correlating with memory function. The literature on fractional anisotropy reductions in the fornix in the clinical spectrum of Alzheimer’s disease from pre-symptomatic carriers of familial Alzheimer’s disease mutations to pre-clinical Alzheimer’s disease, mild cognitive impairment and dementia stages is reviewed.

  12. Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1.

    Science.gov (United States)

    Planche, Vincent; Koubiyr, Ismail; Romero, José E; Manjon, José V; Coupé, Pierrick; Deloire, Mathilde; Dousset, Vincent; Brochet, Bruno; Ruet, Aurélie; Tourdias, Thomas

    2018-04-01

    Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate. We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3 T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques. At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p < .01). After one year, CA4/dentate gyrus atrophy worsened (-6.4%, p < .0001) and significant CA1 atrophy appeared (both in the stratum-pyramidale and the stratum radiatum-lacunosum-moleculare, -5.6%, p < .001 and -6.2%, p < .01, respectively). CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R 2  = 0.44 to 0.47, p < .001, with age, T2 lesion-load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow-up, independently of T2-lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (ß = 0.87, p < .05). The hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal-dependent memory performance. © 2018 Wiley Periodicals, Inc.

  13. Surgical treatment of patients with single and dual pathology: relevance of lesion and of hippocampal atrophy to seizure outcome.

    Science.gov (United States)

    Li, L M; Cendes, F; Watson, C; Andermann, F; Fish, D R; Dubeau, F; Free, S; Olivier, A; Harkness, W; Thomas, D G; Duncan, J S; Sander, J W; Shorvon, S D; Cook, M J; Arnold, D L

    1997-02-01

    Modern neuroimaging can disclose epileptogenic lesions in many patients with partial epilepsy and, at times, display the coexistence of hippocampal atrophy in addition to an extrahippocampal lesion (dual pathology). We studied the postoperative seizure outcome of 64 patients with lesional epilepsy (median follow-up, 30 months) and considered separately the surgical results in the 51 patients with a single lesion and in the 13 who had dual pathology. In patients with a single lesion, 85% were seizure free or significantly improved (Engel's class I-II) when the lesion was totally removed compared with only 40% when there was incomplete resection (p dual pathology who had both the lesion and the atrophic hippocampus removed became seizure free. In contrast, only 2 of the 10 patients with dual pathology undergoing surgery aimed at the lesion or at the hippocampus alone became seizure free (p dual pathology, surgery should, if possible, include resection of both the lesion and the atrophic hippocampus.

  14. Training labels for hippocampal segmentation based on the EADC-ADNI harmonized hippocampal protocol.

    Science.gov (United States)

    Boccardi, Marina; Bocchetta, Martina; Morency, Félix C; Collins, D Louis; Nishikawa, Masami; Ganzola, Rossana; Grothe, Michel J; Wolf, Dominik; Redolfi, Alberto; Pievani, Michela; Antelmi, Luigi; Fellgiebel, Andreas; Matsuda, Hiroshi; Teipel, Stefan; Duchesne, Simon; Jack, Clifford R; Frisoni, Giovanni B

    2015-02-01

    The European Alzheimer's Disease Consortium and Alzheimer's Disease Neuroimaging Initiative (ADNI) Harmonized Protocol (HarP) is a Delphi definition of manual hippocampal segmentation from magnetic resonance imaging (MRI) that can be used as the standard of truth to train new tracers, and to validate automated segmentation algorithms. Training requires large and representative data sets of segmented hippocampi. This work aims to produce a set of HarP labels for the proper training and certification of tracers and algorithms. Sixty-eight 1.5 T and 67 3 T volumetric structural ADNI scans from different subjects, balanced by age, medial temporal atrophy, and scanner manufacturer, were segmented by five qualified HarP tracers whose absolute interrater intraclass correlation coefficients were 0.953 and 0.975 (left and right). Labels were validated as HarP compliant through centralized quality check and correction. Hippocampal volumes (mm(3)) were as follows: controls: left = 3060 (standard deviation [SD], 502), right = 3120 (SD, 897); mild cognitive impairment (MCI): left = 2596 (SD, 447), right = 2686 (SD, 473); and Alzheimer's disease (AD): left = 2301 (SD, 492), right = 2445 (SD, 525). Volumes significantly correlated with atrophy severity at Scheltens' scale (Spearman's ρ = segmentation algorithms. The publicly released labels will allow the widespread implementation of the standard segmentation protocol. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  15. Lateral Fluid Percussion Injury Impairs Hippocampal Synaptic Soluble N-Ethylmaleimide Sensitive Factor Attachment Protein Receptor Complex Formation

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    Shaun W. Carlson

    2017-10-01

    Full Text Available Traumatic brain injury (TBI and the activation of secondary injury mechanisms have been linked to impaired cognitive function, which, as observed in TBI patients and animal models, can persist for months and years following the initial injury. Impairments in neurotransmission have been well documented in experimental models of TBI, but the mechanisms underlying this dysfunction are poorly understood. Formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE complex facilitates vesicular docking and neurotransmitter release in the synaptic cleft. Published studies highlight a direct link between reduced SNARE complex formation and impairments in neurotransmitter release. While alterations in the SNARE complex have been described following severe focal TBI, it is not known if deficits in SNARE complex formation manifest in a model with reduced severity. We hypothesized that lateral fluid percussion injury (lFPI reduces the abundance of SNARE proteins, impairs SNARE complex formation, and contributes to impaired neurobehavioral function. To this end, rats were subjected to lFPI or sham injury and tested for acute motor performance and cognitive function at 3 weeks post-injury. lFPI resulted in motor impairment between 1 and 5 days post-injury. Spatial acquisition and spatial memory, as assessed by the Morris water maze, were significantly impaired at 3 weeks after lFPI. To examine the effect of lFPI on synaptic SNARE complex formation in the injured hippocampus, a separate cohort of rats was generated and brains processed to evaluate hippocampal synaptosomal-enriched lysates at 1 week post-injury. lFPI resulted in a significant reduction in multiple monomeric SNARE proteins, including VAMP2, and α-synuclein, and SNARE complex abundance. The findings in this study are consistent with our previously published observations suggesting that impairments in hippocampal SNARE complex formation may contribute to

  16. Effect of Electroacupuncture on the Expression of Glycyl-tRNA Synthetase and Ultrastructure Changes in Atrophied Rat Peroneus Longus Muscle Induced by Sciatic Nerve Injection Injury

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    Meng Wang

    2016-01-01

    Full Text Available Glycyl-tRNA synthetase (GlyRS is one of the key enzymes involved in protein synthesis. Its mutations have been reported to cause Charcot-Marie-Tooth disease which demonstrates muscular atrophy in distal extremities, particularly manifested in peroneus muscles. In this situation, the dysfunctions of mitochondria and sarcoplasmic reticulum (SR affect energy supply and excitation-contraction coupling of muscle fibers, therefore resulting in muscular atrophy. Although the treatment of muscular atrophy is a global urgent problem, it can be improved by electroacupuncture (EA treatment. To investigate the mechanism underlying EA treatment improving muscular atrophy, we focused on the perspective of protein synthesis by establishing a penicillin injection-induced sciatic nerve injury model. In our model, injured rats without treatment showed decreased sciatic functional index (SFI, decreased peroneus longus muscle weight and muscle fiber cross-sectional area, aggregated mitochondria with vacuoles appearing, swollen SR, and downregulated mRNA and protein expression levels of GlyRS and myosin heavy chain IIb (MHC-IIb. The injured rats with EA treatment showed significant recovery. These results indicated that EA stimulation can alleviate peroneus longus muscular atrophy induced by iatrogenic sciatic nerve injury through promoting the recovery of GlyRS and muscle ultrastructure and increasing muscle protein synthesis.

  17. A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Farjam, Reza [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Pramanik, Priyanka; Aryal, Madhava P. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Srinivasan, Ashok [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Chapman, Christopher H. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Tsien, Christina I. [Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Cao, Yue, E-mail: yuecao@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States)

    2015-11-15

    Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K{sup trans}, and the fraction of blood plasma volume, V{sub p}. The temporal changes in the means of hippocampal transfer constant K{sup trans} and V{sub p} after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K{sup trans} Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.

  18. A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

    International Nuclear Information System (INIS)

    Farjam, Reza; Pramanik, Priyanka; Aryal, Madhava P.; Srinivasan, Ashok; Chapman, Christopher H.; Tsien, Christina I.; Lawrence, Theodore S.; Cao, Yue

    2015-01-01

    Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K"t"r"a"n"s, and the fraction of blood plasma volume, V_p. The temporal changes in the means of hippocampal transfer constant K"t"r"a"n"s and V_p after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K"t"r"a"n"s Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.

  19. Plasticity of hippocampal stem/progenitor cells to enhance neurogenesis in response to kainate-induced injury is lost by middle age

    OpenAIRE

    Hattiangady, Bharathi; Rao, Muddanna S.; Shetty, Ashok K.

    2008-01-01

    A remarkable up-regulation of neurogenesis through increased proliferation of neural stem/progenitor cells (NSCs) is a well-known plasticity displayed by the young dentate gyrus (DG) following brain injury. To ascertain whether this plasticity is preserved during aging, we quantified DG neurogenesis in the young adult, middle-aged and aged F344 rats after kainic acid induced hippocampal injury. Measurement of new cells that are added to the dentate granule cell layer (GCL) between post-injury...

  20. Micro-MRI study of cerebral aging: ex vivo detection of hippocampal sub-field reorganization, micro-hemorrhages and amyloid plaques in mouse lemur primates

    International Nuclear Information System (INIS)

    Bertrand, Anne; Petiet, Alexandra; Dhenain, Marc; Pasquier, Adrien; Kraska, Audrey; Joseph-Mathurin, Nelly; Wiggins, Christopher; Aujard, Fabienne; Mestre-Frances, Nadine

    2013-01-01

    Mouse lemurs are non-human primate models of cerebral aging and neuro-degeneration. Much smaller than other primates, they recapitulate numerous features of human brain aging, including progressive cerebral atrophy and correlation between regional atrophy and cognitive impairments. Characterization of brain atrophy in mouse lemurs has been done by MRI measures of regional CSF volume and by MRI measures of regional atrophy. Here, we further characterize mouse lemur brain aging using ex vivo MR microscopy (31 μm in-plane resolution). First, we performed a non-biased, direct volumetric quantification of dentate gyrus and extended Ammon's horn. We show that both dentate gyrus and Ammon's horn undergo an age-related reorganization leading to a growth of the dentate gyrus and an atrophy of the Ammon's horn, even in the absence of global hippocampal atrophy. Second, on these first MR microscopic images of the mouse lemur brain, we depicted cortical and hippocampal hypointense spots. We demonstrated that their incidence increases with aging and that they correspond either to amyloid deposits or to cerebral micro-hemorrhages. (authors)

  1. Hippocampal sclerosis and status epilepticus: cause or consequence? A MRI study

    International Nuclear Information System (INIS)

    Kuster, Gustavo Wruck; Braga-Neto, Pedro; Santos-Neto, Denizart; Santana, Maria Teresa Garcia; Barsottini, Orlando Graziani; Maia Junior, Antonio Carlos Martins

    2007-01-01

    Background: Transient imaging abnormalities, including changes on diffusion-weighted imaging (DWI), may be seen in status epilepticus. These abnormalities can be followed by hippocampal sclerosis. Case Report: We report a 15-year-old lady with focal non convulsive status epilepticus (NCSE) and focal slowing on EEG. DWI exhibited abnormal hyperintense signals in bilateral temporal and insular cortices. After 3 weeks, MRI performed a localized hippocampal atrophy. Conclusion: The MRI findings indicated vasogenic and cytotoxic edema during seizure activity and subsequent loss of brain parenchyma. (author)

  2. Evoked Potentials and Memory/Cognition Tests Validate Brain Atrophy as Measured by 3T MRI (NeuroQuant in Cognitively Impaired Patients.

    Directory of Open Access Journals (Sweden)

    Eric R Braverman

    Full Text Available To our knowledge, this is the largest study evaluating relationships between 3T Magnetic Resonance Imaging (MRI and P300 and memory/cognitive tests in the literature. The 3T MRI using NeuroQuant has an increased resolution 15 times that of 1.5T MRI. Utilizing NeuroQuant 3T MRI as a diagnostic tool in primary care, subjects (N=169; 19-90 years displayed increased areas of anatomical atrophy: 34.62% hippocampal atrophy (N=54, 57.14% central atrophy (N=88, and 44.52% temporal atrophy (N=69. A majority of these patients exhibited overlap in measured areas of atrophy and were cognitively impaired. These results positively correlated with decreased P300 values and WMS-III (WMS-III scores differentially across various brain loci. Delayed latency (p=0.0740 was marginally associated with temporal atrophy; reduced fractional anisotropy (FA in frontal lobes correlated with aging, delayed P300 latency, and decreased visual and working memory (p=0.0115. Aging and delayed P300 latency correlated with lower FA. The correlation between working memory and reduced FA in frontal lobes is marginally significant (p=0.0787. In the centrum semiovale (CS, reduced FA correlated with visual memory (p=0.0622. Lower demyelination correlated with higher P300 amplitude (p=0.0002. Compared to males, females have higher demyelination (p=0.0064. Along these lines, the higher the P300 amplitude, the lower the bilateral atrophy (p=0.0165. Hippocampal atrophy correlated with increased auditory memory and gender, especially in males (p=0.0087. In considering temporal lobe atrophy correlations: delayed P300 latency and high temporal atrophy (p=0.0740; high auditory memory and low temporal atrophy (p=0.0417; and high working memory and low temporal atrophy (p=0.0166. Central atrophy correlated with aging and immediate memory (p=0.0294: the higher the immediate memory, the lower the central atrophy. Generally, the validation of brain atrophy by P300 and WMS-III could lead to cost

  3. Evoked Potentials and Memory/Cognition Tests Validate Brain Atrophy as Measured by 3T MRI (NeuroQuant) in Cognitively Impaired Patients.

    Science.gov (United States)

    Braverman, Eric R; Blum, Kenneth; Hussman, Karl L; Han, David; Dushaj, Kristina; Li, Mona; Marin, Gabriela; Badgaiyan, Rajendra D; Smayda, Richard; Gold, Mark S

    2015-01-01

    To our knowledge, this is the largest study evaluating relationships between 3T Magnetic Resonance Imaging (MRI) and P300 and memory/cognitive tests in the literature. The 3T MRI using NeuroQuant has an increased resolution 15 times that of 1.5T MRI. Utilizing NeuroQuant 3T MRI as a diagnostic tool in primary care, subjects (N=169; 19-90 years) displayed increased areas of anatomical atrophy: 34.62% hippocampal atrophy (N=54), 57.14% central atrophy (N=88), and 44.52% temporal atrophy (N=69). A majority of these patients exhibited overlap in measured areas of atrophy and were cognitively impaired. These results positively correlated with decreased P300 values and WMS-III (WMS-III) scores differentially across various brain loci. Delayed latency (p=0.0740) was marginally associated with temporal atrophy; reduced fractional anisotropy (FA) in frontal lobes correlated with aging, delayed P300 latency, and decreased visual and working memory (p=0.0115). Aging and delayed P300 latency correlated with lower FA. The correlation between working memory and reduced FA in frontal lobes is marginally significant (p=0.0787). In the centrum semiovale (CS), reduced FA correlated with visual memory (p=0.0622). Lower demyelination correlated with higher P300 amplitude (p=0.0002). Compared to males, females have higher demyelination (p=0.0064). Along these lines, the higher the P300 amplitude, the lower the bilateral atrophy (p=0.0165). Hippocampal atrophy correlated with increased auditory memory and gender, especially in males (p=0.0087). In considering temporal lobe atrophy correlations: delayed P300 latency and high temporal atrophy (p=0.0740); high auditory memory and low temporal atrophy (p=0.0417); and high working memory and low temporal atrophy (p=0.0166). Central atrophy correlated with aging and immediate memory (p=0.0294): the higher the immediate memory, the lower the central atrophy. Generally, the validation of brain atrophy by P300 and WMS-III could lead to cost

  4. Electroacupuncture Improved Hippocampal Neurogenesis following Traumatic Brain Injury in Mice through Inhibition of TLR4 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yuqin Ye

    2017-01-01

    Full Text Available The protective role of electroacupuncture (EA treatment in diverse neurological diseases such as ischemic stroke is well acknowledged. However, whether and how EA act on hippocampal neurogenesis following traumatic brain injury (TBI remains poorly understood. This study aims to investigate the effect of EA on hippocampal neurogenesis and neurological functions, as well as its underlying association with toll-like receptor 4 (TLR4 signaling in TBI mice. BrdU/NeuN immunofluorescence was performed to label newborn neurons in the hippocampus after EA treatment. Water maze test and neurological severity score were used to evaluate neurological function posttrauma. The hippocampal level of TLR4 and downstream molecules and inflammatory cytokines were, respectively, detected by Western blot and enzyme-linked immunosorbent assay. EA enhanced hippocampal neurogenesis and inhibited TLR4 expression at 21, 28, and 35 days after TBI, but the beneficial effects of EA on posttraumatic neurogenesis and neurological functions were attenuated by lipopolysaccharide-induced TLR4 activation. In addition, EA exerted an inhibitory effect on both TLR4/Myd88/NF-κB and TLR4/TRIF/NF-κB pathways, as well as the inflammatory cytokine expression in the hippocampus following TBI. In conclusion, EA promoted hippocampal neurogenesis and neurological recovery through inhibition of TLR4 signaling pathway posttrauma, which may be a potential approach to improve the outcome of TBI.

  5. Protein translation, proteolysis and autophagy in human skeletal muscle atrophy after spinal cord injury.

    Science.gov (United States)

    Lundell, L S; Savikj, M; Kostovski, E; Iversen, P O; Zierath, J R; Krook, A; Chibalin, A V; Widegren, U

    2018-02-08

    Spinal cord injury-induced loss of skeletal muscle mass does not progress linearly. In humans, peak muscle loss occurs during the first 6 weeks postinjury, and gradually continues thereafter. The aim of this study was to delineate the regulatory events underlying skeletal muscle atrophy during the first year following spinal cord injury. Key translational, autophagic and proteolytic proteins were analysed by immunoblotting of human vastus lateralis muscle obtained 1, 3 and 12 months following spinal cord injury. Age-matched able-bodied control subjects were also studied. Several downstream targets of Akt signalling decreased after spinal cord injury in skeletal muscle, without changes in resting Akt Ser 473 and Akt Thr 308 phosphorylation or total Akt protein. Abundance of mTOR protein and mTOR Ser 2448 phosphorylation, as well as FOXO1 Ser 256 phosphorylation and FOXO3 protein, decreased in response to spinal cord injury, coincident with attenuated protein abundance of E3 ubiquitin ligases, MuRF1 and MAFbx. S6 protein and Ser 235/236 phosphorylation, as well as 4E-BP1 Thr 37/46 phosphorylation, increased transiently after spinal cord injury, indicating higher levels of protein translation early after injury. Protein abundance of LC3-I and LC3-II decreased 3 months postinjury as compared with 1 month postinjury, but not compared to able-bodied control subjects, indicating lower levels of autophagy. Proteins regulating proteasomal degradation were stably increased in response to spinal cord injury. Together, these data provide indirect evidence suggesting that protein translation and autophagy transiently increase, while whole proteolysis remains stably higher in skeletal muscle within the first year after spinal cord injury. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  6. Neuronal response of the hippocampal formation to injury: blood flow, glucose metabolism, and protein synthesis

    International Nuclear Information System (INIS)

    Kameyama, M.; Wasterlain, C.G.; Ackermann, R.F.; Finch, D.; Lear, J.; Kuhl, D.E.

    1983-01-01

    The reaction of the hippocampal formation to entorhinal lesions was studied from the viewpoints of cerebral blood flow ([ 123 I]isopropyl-iodoamphetamine[IMP])-glucose utilization ([ 14 C]2-deoxyglucose), and protein synthesis ([ 14 C]leucine), using single- and double-label autoradiography. Researchers' studies showed decreased glucose utilization in the inner part, and increased glucose utilization in the outer part of the molecular layer of the dentate gyrus, starting 3 days after the lesion; increased uptake of [ 123 I]IMP around the lesion from 1 to 3 days postlesion; and starting 3 days after the lesion, marked decrease in [ 14 C]leucine incorporation into proteins and cell loss in the dorsal CA1 and dorsal subiculum in about one-half of the rats. These changes were present only in animals with lesions which invaded the ventral hippocampal formation in which axons of CA1 cells travel. By contrast, transsection of the 3rd and 4th cranial nerves resulted, 3 to 9 days after injury, in a striking increase in protein synthesis in the oculomotor and trochlear nuclei. These results raise the possibility that in some neurons the failure of central regeneration may result from the cell's inability to increase its rate of protein synthesis in response to axonal injury

  7. Hippocampal sclerosis of aging, a prevalent and high-morbidity brain disease

    Science.gov (United States)

    Smith, Charles D.; Abner, Erin L.; Wilfred, Bernard J.; Wang, Wang-Xia; Neltner, Janna H.; Baker, Michael; Fardo, David W.; Kryscio, Richard J.; Scheff, Stephen W.; Jicha, Gregory A.; Jellinger, Kurt A.; Van Eldik, Linda J.; Schmitt, Frederick A.

    2013-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5–30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available. PMID:23864344

  8. Hippocampal atrophy and altered brain responses to pleasant tastes among obese compared with healthy weight children.

    Science.gov (United States)

    Mestre, Z L; Bischoff-Grethe, A; Eichen, D M; Wierenga, C E; Strong, D; Boutelle, K N

    2017-10-01

    The hippocampus is a key structure implicated in food motivation and intake. Research has shown that the hippocampus is vulnerable to the consumption of a western diet (i.e., high saturated fat and simple carbohydrates). Studies of patients with obesity (OB), compared with healthy weight (HW), show changes in hippocampal volume and response to food cues. Moreover, evidence suggests that OB children, relative to HW, have greater hippocampal response to taste. However, no study has examined the association of hippocampal volume with taste functioning in children. We hypothesized that OB children, relative to HW, would show a significant reduction in hippocampal volume and that decreased volume would be significantly associated with greater activation to taste. Finally, we explored whether hippocampal activation would be associated with measures on eating and eating habits. Twenty-five 8-12-year-old children (i.e., 13 HW, 12 OB) completed a magnetic resonance imaging scan while participating in a taste paradigm (i.e., 1 ml of 10% sucrose or ionic water delivered pseudorandomly every 20 s). Children with OB, relative to HW, showed reduced left hippocampal volume (t=1.994, P=0.03, 95% confidence interval (CI)=-40.23,  755.42), and greater response to taste in three clusters within the left hippocampus (z=3.3, P=0.001, 95% CI=-0.241, -0.041; z=3.3, P=0.001, 95% CI=-0.2711, -0.0469; z=2.7, P=0.007, 95% CI=-0.6032, -0.0268). Activation within the hippocampus was associated with eating in the absence of hunger (EAH%; t=2.408, P=0.025, 95% CI= 1.751708, 23.94109) and two subscales on a measure of eating behaviors (Food responsiveness, t=2.572, P=0.017, 95% CI= 0.9565195, 9.043440; Food enjoyment, t=2.298, P=0.032, 95% CI=0.2256749, 4.531298). As hypothesized, OB children, relative to HW, had significantly reduced hippocampal volume, and greater hippocampal activation to taste. Moreover, hippocampal activation was associated with measures of eating. These results

  9. [Evaluation of diffuse cerebral atrophy in patients with a history of traumatic brain injury and its relation to cognitive deterioration].

    Science.gov (United States)

    Narberhaus, A; Segarra-Castells, M D; Verger-Maestre, K; Serra-Grabulosa, J M; Salgado-Pineda, P; Bartomeus-Jené, F; Mercader-Sobrequés, J M

    Diffuse damage secondary to traumatic brain injury (TBI) can be studied through volumetric analysis of several structures that are sensible to this kind of injury, such as corpus callosum, ventricular system, hippocampus, basal ganglia and the volume of cerebrospinal fluid spaces. Our aim is to describe how closed head injury (CHI) occurred in early years produce diffuse damage, and how this damage affects general cognitive functioning at long term. Initially the group of subjects was composed of 27 head injured children and adolescents following paediatric moderate to severe TBI. From this initial group we selected 15 patients without focal lesion, or in case of having suffered focal lesion, this was smaller than 2,600 mm3. These subjects were assessed by means of volumetric analysis of cerebrospinal fluid spaces, corpus callosum, hippocampus and caudate nucleus, comparing the results with a matched control group. We calculated the degree of general cognitive ability of these subjects through tests of intellectual, memory, frontal lobe and motor speed functioning. This study demonstrates that early CHI produce a volume decrease in all measured structures. Corpus callosum atrophy is the factor that better explains general cognitive impairment. Diffuse damage secondary to moderate to severe peadiatric TBI has long term effects on several cerebral structures and on cognitive performance. Corpus callosum atrophy is the best predictor for general cognitive impairment, compared with other affected structures.

  10. Predicting memory performance in normal ageing using different measures of hippocampal size

    International Nuclear Information System (INIS)

    Lye, T.C.; Creasey, H.; Kril, J.J.; Grayson, D.A.; Piguet, O.; Bennett, H.P.; Ridley, L.J.; Broe, G.A.

    2006-01-01

    A number of different methods have been employed to correct hippocampal volumes for individual variation in head size. Researchers have previously used qualitative visual inspection to gauge hippocampal atrophy. The purpose of this study was to determine the best measure(s) of hippocampal size for predicting memory functioning in 102 community-dwelling individuals over 80 years of age. Hippocampal size was estimated using magnetic resonance imaging (MRI) volumetry and qualitative visual assessment. Right and left hippocampal volumes were adjusted by three different estimates of head size: total intracranial volume (TICV), whole-brain volume including ventricles (WB+V) and a more refined measure of whole-brain volume with ventricles extracted (WB). We compared the relative efficacy of these three volumetric adjustment methods and visual ratings of hippocampal size in predicting memory performance using linear regression. All four measures of hippocampal size were significant predictors of memory performance. TICV-adjusted volumes performed most poorly in accounting for variance in memory scores. Hippocampal volumes adjusted by either measure of whole-brain volume performed equally well, although qualitative visual ratings of the hippocampus were at least as effective as the volumetric measures in predicting memory performance in community-dwelling individuals in the ninth or tenth decade of life. (orig.)

  11. Alzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936.

    Directory of Open Access Journals (Sweden)

    Donald M Lyall

    Full Text Available The APOE ε and TOMM40 rs10524523 ('523' variable length poly-T repeat gene loci have been significantly and independently associated with Alzheimer's disease (AD related phenotypes such as age of clinical onset. Hippocampal atrophy has been significantly associated with memory impairment, a characteristic of AD. The current study aimed to test for independent effects of APOE ε and TOMM40 '523' genotypes on hippocampal volumes as assessed by brain structural MRI in a relatively large sample of community-dwelling older adults. As part of a longitudinal study of cognitive ageing, participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε2/ε3/ε4 status and TOMM40 '523' poly-T repeat length, and detailed structural brain MRI at a mean age of 72.7 years (standard deviation = 0.7, N range = 624 to 636. No significant effects of APOE ε or TOMM40 523 genotype were found on hippocampal volumes when analysed raw, or when adjusted for either intracranial or total brain tissue volumes. In summary, in a large community-dwelling sample of older adults, we found no effects of APOE ε or TOMM40 523 genotypes on hippocampal volumes. This is discrepant with some previous reports of significant association between APOE and left/right hippocampal volumes, and instead echoes other reports that found no association. Previous significant findings may partly reflect type 1 error. Future studies should carefully consider: 1 their specific techniques in adjusting for brain size; 2 assessing more detailed sub-divisions of the hippocampal formation; and 3 testing whether significant APOE-hippocampal associations are independent of generalised brain atrophy.

  12. Spectroscopic evidence of hippocampal abnormalities in neocortical epilepsy

    Science.gov (United States)

    Mueller, S. G.; Laxer, K. D.; Cashdollar, N.; Lopez, R. C.; Weiner, M. W.

    2009-01-01

    Lesional neocortical epilepsy (NE) can be associated with hippocampal sclerosis or hippocampal spectroscopic abnormalities without atrophy (dual pathology). In this study, magnetic resonance spectroscopic imaging (MRSI) was used to determine the frequency of hippocampal damage/dysfunction in NE with and without structural lesion. Sixteen patients with NE [seven temporal NE (NE-T), nine extratemporal (NE-ET)] and 16 controls were studied with a 2D MRSI sequence (Repetition time/echo time (TR/TE) = 1800/135 ms) covering both hippocampi. Seven NE patients had MR visible lesions (NE-Les), nine had normal MRI (NE-no). In each hippocampus, 12 voxels were uniformly selected. In controls, mean (± SD) NAA/(Cr + Cho) values for each voxel were calculated and voxels with NAA/(Cr + Cho) ≤ (mean in controls – 2SD in controls) were defined as ‘pathological’ in patients. Eight of 16 NE patients had at least two ‘pathological’ voxel (mean 2.5, range 2–5) in one hippocampus. Four were NE-Les and four NE-no. Three (43%) NE-T patients, had evidence for hippocampal damage/dysfunction and five (56%) had NE-ET. The ipsilateral hippocampus was affected in six of eight NE patients. Evidence for unilateral hippocampal damage/dysfunction was demonstrated in 50% of the NE patients. The type of NE, i.e. NE-Les or NE-no, NE-T or NE-ET, had no influence on the occurrence of hippocampal damage/dysfunction. PMID:16618342

  13. Crossed cerebellar atrophy in children: a neurologic sequela of extreme prematurity

    International Nuclear Information System (INIS)

    Rollins, N.K.; Wen, T.S.; Dominguez, R.

    1995-01-01

    We retrospectively identified eight children, aged 8 months to 13 years, in whom cerebellar atrophy associated with cerebral injury was diagnosed on MR or CT, and reviewed their past medical history, neurologic findings, and neuroimaging studies. Seven patients were born extremely premature, EGA 25-28 weeks, and had severe perinatal intracranial hemorrhage. Neurologic problems include severe developmental delay in seven, spastic paresis in six, and seizures in five. Neuroimaging showed severe unilaterial holohemispheric atrophy in four, bilateral asymmetric holohemispheric atrophy in two, and left temporoparietal atrophy in one. Cerebellar atrophy was unilateral in five and bilateral but asymmetric in two. Gliosis of the atrophic cerebellum occurred in one patient. Sequential neuroimaging in one patient showed evolution of crossed cerebellar atrophy at 8 months of age. The final patient, a term infant, had an idiopathic perinatal left cerebral infarct. (orig./MG)

  14. Delayed recall, hippocampal volume and Alzheimer neuropathology: findings from the Nun Study.

    Science.gov (United States)

    Mortimer, J A; Gosche, K M; Riley, K P; Markesbery, W R; Snowdon, D A

    2004-02-10

    To examine the associations of hippocampal volume and the severity of neurofibrillary lesions determined at autopsy with delayed verbal recall performance evaluated an average of 1 year prior to death. Hippocampal volumes were computed using postmortem brain MRI from the first 56 scanned participants of the Nun Study. Quantitative neuropathologic studies included lesion counts, Braak staging, and determination of whether neuropathologic criteria for Alzheimer disease (AD) were met. Multiple regression was used to assess the association of hippocampal volume and neuropathologic lesions with the number of words (out of 10) recalled on the Consortium to Establish a Registry for Alzheimer's Disease Delayed Word Recall Test administered an average of 1 year prior to death. When entered separately, hippocampal volume, Braak stage, and the mean neurofibrillary tangle counts in the CA-1 region of the hippocampus and the subiculum were strongly associated with the number of words recalled after a delay, adjusting for age and education. When hippocampal volume was entered together with each neuropathologic index, only hippocampal volume retained a significant association with the delayed recall measure. The association between hippocampal volume and the number of words recalled was present in both demented and nondemented individuals as well as in those with and without substantial AD neurofibrillary pathology. The association of neurofibrillary tangles with delayed verbal recall may reflect associated hippocampal atrophy.

  15. Salvianolic Acids Attenuate Rat Hippocampal Injury after Acute CO Poisoning by Improving Blood Flow Properties

    Directory of Open Access Journals (Sweden)

    Li Guan

    2015-01-01

    Full Text Available Carbon monoxide (CO poisoning causes the major injury and death due to poisoning worldwide. The most severe damage via CO poisoning is brain injury and mortality. Delayed encephalopathy after acute CO poisoning (DEACMP occurs in forty percent of the survivors of acute CO exposure. But the pathological cause for DEACMP is not well understood. And the corresponding therapy is not well developed. In order to investigate the effects of salvianolic acid (SA on brain injury caused by CO exposure from the view point of hemorheology, we employed a rat model and studied the dynamic of blood changes in the hemorheological and coagulative properties over acute CO exposure. Compared with the groups of CO and 20% mannitol + CO treatments, the severe hippocampal injury caused by acute CO exposure was prevented by SA treatment. These protective effects were associated with the retaining level of hematocrit (Hct, plasma viscosity, fibrinogen, whole blood viscosities and malondialdehyde (MDA levels in red blood cells (RBCs. These results indicated that SA treatment could significantly improve the deformation of erythrocytes and prevent the damage caused by CO poisoning. Meanwhile, hemorheological indexes are good indicators for monitoring the pathological dynamic after acute CO poisoning.

  16. MRI of rotator cuff muscle atrophy in relation to glenohumeral joint incongruence in brachial plexus birth injury

    International Nuclear Information System (INIS)

    Poeyhiae, Tiina H.; Nietosvaara, Yrjaenae A.; Peltonen, Jari I.; Remes, Ville M.; Kirjavainen, Mikko O.; Lamminen, Antti E.

    2005-01-01

    Purpose: To evaluate rotator cuff muscles and the glenohumeral (GH) joint in brachial plexus birth injury (BPBI) using MRI and to determine whether any correlation exists between muscular abnormality and the development of glenoid dysplasia and GH joint incongruity. Thirty-nine consecutive BPBI patients with internal rotation contracture or absent active external rotation of the shoulder joint were examined clinically and imaged with MRI. In the physical examination, passive external rotation was measured to evaluate internal rotation contracture. Both shoulders were imaged and the glenoscapular angle, percentage of humeral head anterior to the middle of the glenoid fossa (PHHA) and the greatest thickness of the subscapular, infraspinous and supraspinous muscles were measured. The muscle ratio between the affected side and the normal side was calculated to exclude age variation in the assessment of muscle atrophy. All muscles of the rotator cuff were atrophic, with the subscapular and infraspinous muscles being most severely affected. A correlation was found between the percentage of humeral head anterior to the middle of the glenoid fossa (PHHA) and the extent of subscapular muscle atrophy (r s =0.45, P=0.01), as well as between its ratio (r s =0.5, P P=0.01). Severity of rotator cuff muscle atrophy correlated with increased glenoid retroversion and the degree of internal rotation contracture. Glenoid retroversion and subluxation of the humeral head are common in patients with BPBI. All rotator cuff muscles are atrophic, especially the subscapular muscle. Muscle atrophy due to neurogenic damage apparently results in an imbalance of the shoulder muscles and progressive retroversion and subluxation of the GH joint, which in turn lead to internal rotation contracture and deformation of the joint. (orig.)

  17. Preliminary evidence of hippocampal damage in chronic users of ecstasy.

    Science.gov (United States)

    den Hollander, Bjørnar; Schouw, Marieke; Groot, Paul; Huisman, Henk; Caan, Matthan; Barkhof, Frederik; Reneman, Liesbeth

    2012-01-01

    Various studies have shown that ecstasy (3,4-methylenedioxymethamphetamine) users display significant memory impairments, whereas their performance on other cognitive tests is generally normal. The hippocampus plays an essential role in short-term memory. There are, however, no structural human data on the effects of ecstasy on the hippocampus. The objective of this study was to investigate whether the hippocampal volume of chronic ecstasy users is reduced when compared with healthy polydrug-using controls, as an indicator of hippocampal damage. The hippocampus was manually outlined in volumetric MRI scans in 10 male ecstasy users (mean age 25.4 years) and seven healthy age- and gender-matched control subjects (21.3 years). Other than the use of ecstasy, there were no statistically significant differences between both groups in exposure to other drugs of abuse and alcohol. The ecstasy users were on average drug-free for more than 2 months and had used on average 281 tablets over the past six and a half years. The hippocampal volume in the ecstasy using group was on average 10.5% smaller than the hippocampal volume in the control group (p=0.032). These data provide preliminary evidence that ecstasy users may be prone to incurring hippocampal damage, in line with previous reports of acute hippocampal sclerosis and subsequent atrophy in chronic users of this drug.

  18. Decreased hippocampal volume, indirectly measured, is associated with depressive symptoms and consolidation deficits in multiple sclerosis

    NARCIS (Netherlands)

    Kiy, G.; Lehmann, P.; Hahn, H.K.; Eling, P.A.T.M.; Kastrup, A.; Hildebrandt, H.

    2011-01-01

    Background: The human hippocampus plays a role in episodic memory and depression. Recently, it has been shown, using manual tracings, that the hippocampus is smaller in volume in MS patients compared with healthy controls, and that, at least for depression, hippocampal atrophy correlates with

  19. Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study

    DEFF Research Database (Denmark)

    Korf, E S C; van Straaten, E C W; de Leeuw, F-E

    2007-01-01

    HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white...... matter hyperintensities. METHODS: In the Leukoaraiosis And DISability in the elderly (LADIS) study, we investigated the relationships between DM, hypertension, blood pressure and MTA in 582 subjects, stratified by white matter hyperintensity severity, using multinomial logistic regression. MTA...... was visually scored for the left and right medial temporal lobe (score 0-4), and meaned. RESULTS: Mean age was 73.5 years (sd 5.1), 54% was female. Of the subjects, 15% had DM, and 70% had a history of hypertension. The likelihood of having MTA score 3 was significantly higher in subjects with DM (OR 2.9; 95...

  20. Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury

    International Nuclear Information System (INIS)

    Chen, Shang-Der; Lin, Tsu-Kung; Yang, Ding-I.; Lee, Su-Ying; Shaw, Fu-Zen; Liou, Chia-Wei; Chuang, Yao-Chung

    2015-01-01

    Recent studies showed that increased mitochondrial fission is an early event of cell death during cerebral ischemia and dynamin-related protein 1 (Drp1) plays an important role in mitochondrial fission, which may be regulated by PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase thought to protect cells from stress-induced mitochondrial dysfunction and regulate mitochondrial fission. However, the roles of PINK1 and Drp1 in hippocampal injury caused by transient global ischemia (TGI) remain unknown. We therefore tested the hypothesis that TGI may induce PINK1 causing downregulation of Drp1 phosphorylation to enhance hippocampal neuronal survival, thus functioning as an endogenous neuroprotective mechanism. We found progressively increased PINK1 expression in the hippocampal CA1 subfield1-48 h following TGI, reaching the maximal level at 4 h. Despite lack of changes in the expression level of total Drp1 and phosphor-Drp1 at Ser637, TGI induced a time-dependent increase of Drp1 phosphorlation at Ser616 that peaked after 24 h. Notably, PINK1-siRNA increased p-Drp1(Ser616) protein level in hippocampal CA1 subfield 24 h after TGI. The PINK1 siRNA also aggravated the TGI-induced oxidative DNA damage with an increased 8-hydroxy-deoxyguanosine (8-OHdG) content in hippocampal CA1 subfield. Furthermore, PINK1 siRNA also augmented TGI-induced apoptosis as evidenced by the increased numbers of TUNEL-positive staining and enhanced DNA fragmentation. These findings indicated that PINK1 is an endogenous protective mediator vital for neuronal survival under ischemic insult through regulating Drp1 phosphorylation at Ser616. - Highlights: • Transient global ischemia increases expression of PINK1 and p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA decreases PINK1 expression but increases p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA augments oxidative stress and neuronal damage in hippocampal CA1 subfield

  1. Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shang-Der, E-mail: chensd@adm.cgmh.org.tw [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Lin, Tsu-Kung [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Yang, Ding-I. [Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan (China); Lee, Su-Ying [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Shaw, Fu-Zen [Department of Psychology, National Cheng Kung University, Tainan, Taiwan (China); Liou, Chia-Wei [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Chuang, Yao-Chung, E-mail: ycchuang@adm.cgmh.org.tw [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China)

    2015-05-01

    Recent studies showed that increased mitochondrial fission is an early event of cell death during cerebral ischemia and dynamin-related protein 1 (Drp1) plays an important role in mitochondrial fission, which may be regulated by PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase thought to protect cells from stress-induced mitochondrial dysfunction and regulate mitochondrial fission. However, the roles of PINK1 and Drp1 in hippocampal injury caused by transient global ischemia (TGI) remain unknown. We therefore tested the hypothesis that TGI may induce PINK1 causing downregulation of Drp1 phosphorylation to enhance hippocampal neuronal survival, thus functioning as an endogenous neuroprotective mechanism. We found progressively increased PINK1 expression in the hippocampal CA1 subfield1-48 h following TGI, reaching the maximal level at 4 h. Despite lack of changes in the expression level of total Drp1 and phosphor-Drp1 at Ser637, TGI induced a time-dependent increase of Drp1 phosphorlation at Ser616 that peaked after 24 h. Notably, PINK1-siRNA increased p-Drp1(Ser616) protein level in hippocampal CA1 subfield 24 h after TGI. The PINK1 siRNA also aggravated the TGI-induced oxidative DNA damage with an increased 8-hydroxy-deoxyguanosine (8-OHdG) content in hippocampal CA1 subfield. Furthermore, PINK1 siRNA also augmented TGI-induced apoptosis as evidenced by the increased numbers of TUNEL-positive staining and enhanced DNA fragmentation. These findings indicated that PINK1 is an endogenous protective mediator vital for neuronal survival under ischemic insult through regulating Drp1 phosphorylation at Ser616. - Highlights: • Transient global ischemia increases expression of PINK1 and p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA decreases PINK1 expression but increases p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA augments oxidative stress and neuronal damage in hippocampal CA1 subfield.

  2. Fluoxetine Increases Hippocampal Neurogenesis and Induces Epigenetic Factors But Does Not Improve Functional Recovery after Traumatic Brain Injury

    Science.gov (United States)

    Wang, Yonggang; Neumann, Melanie; Hansen, Katharina; Hong, Shuwhey M.; Kim, Sharon; Noble-Haeusslein, Linda J.

    2011-01-01

    Abstract The selective serotonin reuptake inhibitor fluoxetine induces hippocampal neurogenesis, stimulates maturation and synaptic plasticity of adult hippocampal neurons, and reduces motor/sensory and memory impairments in several CNS disorders. In the setting of traumatic brain injury (TBI), its effects on neuroplasticity and function have yet to be thoroughly investigated. Here we examined the efficacy of fluoxetine after a moderate to severe TBI, produced by a controlled cortical impact. Three days after TBI or sham surgery, mice were treated with fluoxetine (10 mg/kg/d) or vehicle for 4 weeks. To evaluate the effects of fluoxetine on neuroplasticity, hippocampal neurogenesis and epigenetic modification were studied. Stereologic analysis of the dentate gyrus revealed a significant increase in doublecortin-positive cells in brain-injured animals treated with fluoxetine relative to controls, a finding consistent with enhanced hippocampal neurogenesis. Epigenetic modifications, including an increase in histone 3 acetylation and induction of methyl-CpG-binding protein, a transcription factor involved in DNA methylation, were likewise seen by immunohistochemistry and quantitative Western immunoblots, respectively, in brain-injured animals treated with fluoxetine. To determine if fluoxetine improves neurological outcomes after TBI, gait function and spatial learning and memory were assessed by the CatWalk-assisted gait test and Barnes maze test, respectively. No differences in these parameters were seen between fluoxetine- and vehicle-treated animals. Thus while fluoxetine enhanced neuroplasticity in the hippocampus after TBI, its chronic administration did not restore locomotor function or ameliorate memory deficits. PMID:21175261

  3. Subacute brain atrophy induced by radiation therapy to the malignant brain tumors

    International Nuclear Information System (INIS)

    Asai, Akio; Matsutani, Masao; Takakura, Kintomo.

    1987-01-01

    In order to analyze brain atrophy after radiation therapy to the brain tumors, we calculated a CSF-cranial volume ratio on CT scan as an index of brain atrophy, and estimated dementia-score by Hasegawa's method in 91 post-irradiated patients with malignant brain tumors. Radiation-induced brain atrophy was observed in 51 out of 91 patients (56 %) and dementia in 23 out of 47 patients (49 %). These two conditions were closely related, and observed significantly more often in aged and whole-brain-irradiated patients. As radiation-induced brain atrophy accompanied by dementia appeared 2 - 3 months after the completion of radiation therapy, it should be regarded as a subacute brain injury caused by radiation therapy. (author)

  4. A meta-analysis on progressive atrophy in intractable temporal lobe epilepsy

    Science.gov (United States)

    Caciagli, Lorenzo; Bernasconi, Andrea; Wiebe, Samuel; Koepp, Matthias J.; Bernasconi, Neda

    2017-01-01

    Objective: It remains unclear whether drug-resistant temporal lobe epilepsy (TLE) is associated with cumulative brain damage, with no expert consensus and no quantitative syntheses of the available evidence. Methods: We conducted a systematic review and meta-analysis of MRI studies on progressive atrophy, searching PubMed and Ovid MEDLINE databases for cross-sectional and longitudinal quantitative MRI studies on drug-resistant TLE. Results: We screened 2,976 records and assessed eligibility of 248 full-text articles. Forty-two articles met the inclusion criteria for quantitative evaluation. We observed a predominance of cross-sectional studies, use of different clinical indices of progression, and high heterogeneity in age-control procedures. Meta-analysis of 18/1 cross-sectional/longitudinal studies on hippocampal atrophy (n = 979 patients) yielded a pooled effect size of r = −0.42 for ipsilateral atrophy related to epilepsy duration (95% confidence interval [CI] −0.51 to −0.32; p 80% of articles reported duration-related progression in extratemporal cortical and subcortical regions. Detailed analysis of study design features yielded low to moderate levels of evidence for progressive atrophy across studies, mainly due to dominance of cross-sectional over longitudinal investigations, use of diverse measures of seizure estimates, and absence of consistent age control procedures. Conclusions: While the neuroimaging literature is overall suggestive of progressive atrophy in drug-resistant TLE, published studies have employed rather weak designs to directly demonstrate it. Longitudinal multicohort studies are needed to unequivocally differentiate aging from disease progression. PMID:28687722

  5. Long-Term Treatment with Paroxetine Increases Verbal Declarative Memory and Hippocampal Volume in Posttraumatic Stress Disorder

    Science.gov (United States)

    Vermetten, Eric; Vythilingam, Meena; Southwick, Steven M.; Charney, Dennis S.; Bremner, J. Douglas

    2011-01-01

    Background Animal studies have shown that stress is associated with damage to the hippocampus, inhibition of neurogenesis, and deficits in hippocampal-based memory dysfunction. Studies in patients with posttraumatic stress disorder (PTSD) found deficits in hippocampal-based declarative verbal memory and smaller hippocampal volume, as measured with magnetic resonance imaging (MRI). Recent preclinical evidence has shown that selective serotonin reuptake inhibitors promote neurogenesis and reverse the effects of stress on hippocampal atrophy. This study assessed the effects of long-term treatment with paroxetine on hippocampal volume and declarative memory performance in PTSD. Methods Declarative memory was assessed with the Wechsler Memory Scale–Revised and Selective Reminding Test before and after 9–12 months of treatment with paroxetine in PTSD. Hippocampal volume was measured with MRI. Of the 28 patients who started the protocol, 23 completed the full course of treatment and neuropsychological testing. Twenty patients were able to complete MRI imaging. Results Patients with PTSD showed a significant improvement in PTSD symptoms with treatment. Treatment resulted in significant improvements in verbal declarative memory and a 4.6% increase in mean hippocampal volume. Conclusions These findings suggest that long-term treatment with paroxetine is associated with improvement of verbal declarative memory deficits and an increase in hippocampal volume in PTSD. PMID:14512209

  6. Atrophy of the brachialis muscle after a displaced clavicle fracture in an Ironman triathlete: case report

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    Knechtle Patrizia

    2011-10-01

    Full Text Available Abstract Clavicle fractures are frequent injuries in athletes and midshaft clavicle fractures in particular are well-known injuries in Ironman triathletes. In 2000, Auzou et al. described the mechanism leading to an isolated truncular paralysis of the musculocutaneous nerve after a shoulder trauma. It is well-known that nerve palsies can lead to an atrophy of the associated muscle if they persist for months or even longer. In this case report we describe a new case of an Ironman triathlete suffering from a persistent isolated atrophy of the brachialis muscle. The atrophy occurred following a displaced midshaft clavicle fracture acquiring while falling off his bike after hitting a duck during a competition.

  7. Associative reinstatement memory measures hippocampal function in Parkinson's Disease.

    Science.gov (United States)

    Cohn, Melanie; Giannoylis, Irene; De Belder, Maya; Saint-Cyr, Jean A; McAndrews, Mary Pat

    2016-09-01

    In Parkinson's Disease (PD), hippocampal atrophy is associated with rapid cognitive decline. Hippocampal function is typically assessed using memory tests but current clinical tools (e.g., free recall) also rely on executive functions or use material that is not optimally engaging hippocampal memory networks. Because of the ubiquity of executive dysfunction in PD, our ability to detect true memory deficits is suboptimal. Our previous behavioural and neuroimaging work in other populations suggests that an experimental memory task - Associative Reinstatement Memory (ARM) - may prove useful in investigating hippocampal function in PD. In this study, we investigated whether ARM is compromised in PD and we assessed its convergent and divergent validity by comparing it to standardized measures of memory and of attention and executive functioning in PD, respectively. Using fMRI, we also investigated whether performance in PD relates to degree of hippocampal engagement. Fifteen participants with PD and 13 age-matched healthy controls completed neuropsychological testing as well as an ARM fMRI recognition paradigm in which they were instructed to identify word pairs comprised of two studied words (intact or rearranged pairs) and those containing at least one new word (new or half new pairs). ARM is measured by the differences in hit rates between intact and rearranged pairs. Behaviourally, ARM was poorer in PD relative to controls and was correlated with verbal memory measures, but not with attention or executive functioning in the PD group. Hippocampal activation associated with ARM was reduced in PD relative to controls and covaried with ARM scores in both groups. To conclude, ARM is a sensitive measure of hippocampal memory function that is unaffected by attention or executive dysfunction in PD. Our study highlights the benefit of integrating cognitive neuroscience frameworks and novel experimental tasks to improve the practice of clinical neuropsychology in PD

  8. The effects of hormones and physical exercise on hippocampal structural plasticity.

    Science.gov (United States)

    Triviño-Paredes, Juan; Patten, Anna R; Gil-Mohapel, Joana; Christie, Brian R

    2016-04-01

    The hippocampus plays an integral role in certain aspects of cognition. Hippocampal structural plasticity and in particular adult hippocampal neurogenesis can be influenced by several intrinsic and extrinsic factors. Here we review how hormones (i.e., intrinsic modulators) and physical exercise (i.e., an extrinsic modulator) can differentially modulate hippocampal plasticity in general and adult hippocampal neurogenesis in particular. Specifically, we provide an overview of the effects of sex hormones, stress hormones, and metabolic hormones on hippocampal structural plasticity and adult hippocampal neurogenesis. In addition, we also discuss how physical exercise modulates these forms of hippocampal plasticity, giving particular emphasis on how this modulation can be affected by variables such as exercise regime, duration, and intensity. Understanding the neurobiological mechanisms underlying the modulation of hippocampal structural plasticity by intrinsic and extrinsic factors will impact the design of new therapeutic approaches aimed at restoring hippocampal plasticity following brain injury or neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Hippocampal sclerosis dementia: An amnesic variant of frontotemporal degeneration

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    Chiadi U. Onyike

    Full Text Available ABSTRACT Objective: To describe characteristics of hippocampal sclerosis dementia. Methods: Convenience sample of Hippocampal sclerosis dementia (HSD recruited from the Johns Hopkins University Brain Resource Center. Twenty-four cases with post-mortem pathological diagnosis of hippocampal sclerosis dementia were reviewed for clinical characterization. Results: The cases showed atrophy and neuronal loss localized to the hippocampus, amygdala and entorrhinal cortex. The majority (79.2% had amnesia at illness onset, and many (54.2% showed abnormal conduct and psychiatric disorder. Nearly 42% presented with an amnesic state, and 37.5% presented with amnesia plus abnormal conduct and psychiatric disorder. All eventually developed a behavioral or psychiatric disorder. Disorientation, executive dysfunction, aphasia, agnosia and apraxia were uncommon at onset. Alzheimer disease (AD was the initial clinical diagnosis in 89% and the final clinical diagnosis in 75%. Diagnosis of frontotemporal dementia (FTD was uncommon (seen in 8%. Conclusion: HSD shows pathological characteristics of FTD and clinical features that mimic AD and overlap with FTD. The findings, placed in the context of earlier work, support the proposition that HSD belongs to the FTD family, where it may be identified as an amnesic variant.

  10. Hippocampal sclerosis dementia: an amnesic variant of frontotemporal degeneration

    Science.gov (United States)

    Onyike, Chiadi U.; Pletnikova, Olga; Sloane, Kelly L.; Sullivan, Campbell; Troncoso, Juan C.; Rabins, Peter V.

    2013-01-01

    OBJECTIVE To describe characteristics of hippocampal sclerosis dementia. METHODS Convenience sample of Hippocampal sclerosis dementia (HSD) recruited from the Johns Hopkins University Brain Resource Center. Twenty-four cases with post-mortem pathological diagnosis of hippocampal sclerosis dementia were reviewed for clinical characterization. RESULTS The cases showed atrophy and neuronal loss localized to the hippocampus, amygdala and entorrhinal cortex. The majority (79.2%) had amnesia at illness onset, and many (54.2%) showed abnormal conduct and psychiatric disorder. Nearly 42% presented with an amnesic state, and 37.5% presented with amnesia plus abnormal conduct and psychiatric disorder. All eventually developed a behavioral or psychiatric disorder. Disorientation, executive dysfunction, aphasia, agnosia and apraxia were uncommon at onset. Alzheimer disease (AD) was the initial clinical diagnosis in 89% and the final clinical diagnosis in 75%. Diagnosis of frontotemporal dementia (FTD) was uncommon (seen in 8%). CONCLUSION HSD shows pathological characteristics of FTD and clinical features that mimic AD and overlap with FTD. The findings, placed in the context of earlier work, support the proposition that HSD belongs to the FTD family, where it may be identified as an amnesic variant. PMID:24363834

  11. Precuneus atrophy in early-onset Alzheimer's disease: a morphometric structural MRI study

    International Nuclear Information System (INIS)

    Karas, Giorgos; Scheltens, Philip; Jones, Bethany; Rombouts, Serge; Schijndel, Ronald van; Klein, Martin; Flier, Wiesje van der; Vrenken, Hugo; Barkhof, Frederik

    2007-01-01

    Alzheimer's disease (AD) usually first presents in elderly patients, but may also develop at an earlier age. Patients with an early age at onset tend to present with complaints other than memory impairment, such as visuospatial problems or apraxia, which may reflect a different distribution of cortical involvement. In this study we set out to investigate whether age at onset in patients with AD determines the pattern of atrophy on cerebral MRI scans. We examined 55 patients with AD over a wide age range and analyzed their 3-D T1-weighted structural MRI scans in standard space using voxel-based morphometry (VBM). Regression analysis was performed to estimate loss of grey matter as a function of age, corrected for mini-mental state examination (MMSE) scores and sex. The VBM analyses identified multiple areas (including the temporal and parietal lobes), showing more atrophy with advancing age. By contrast, a younger age at onset was found to be associated with lower grey matter density in the precuneus. Regionalized volumetric analysis of this region confirmed the existence of disproportionate atrophy in the precuneus in patients with early-onset AD. Application of a multivariate model with precuneus grey matter density as input, showed that precuneal and hippocampal atrophy are independent from each other. Additionally, we found that a smaller precuneus is associated with impaired visuospatial functioning. Our findings support the notion that age at onset modulates the distribution of cortical involvement, and that disproportionate precuneus atrophy is more prominent in patients with a younger age of onset. (orig.)

  12. Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: preliminary findings.

    Science.gov (United States)

    Leavitt, V M; Cirnigliaro, C; Cohen, A; Farag, A; Brooks, M; Wecht, J M; Wylie, G R; Chiaravalloti, N D; DeLuca, J; Sumowski, J F

    2014-01-01

    Multiple sclerosis leads to prominent hippocampal atrophy, which is linked to memory deficits. Indeed, 50% of multiple sclerosis patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for multiple sclerosis either pharmacological or behavioral. Aerobic exercise improves memory and promotes hippocampal neurogenesis in nonhuman animals. Here, we investigate the benefits of aerobic exercise in memory-impaired multiple sclerosis patients. Pilot data were collected from two ambulatory, memory-impaired multiple sclerosis participants randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. The following baseline/follow-up measurements were taken: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30-minute sessions 3 times per week for 3 months. Aerobic exercise resulted in 16.5% increase in hippocampal volume and 53.7% increase in memory, as well as increased hippocampal resting-state functional connectivity. Improvements were specific, with no comparable changes in overall cerebral gray matter (+2.4%), non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), or in non-memory cognitive functioning (executive functions, processing speed, working memory: changes ranged from -11% to +4%). Non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal functional connectivity. This is the first evidence for aerobic exercise to increase hippocampal volume and connectivity and improve memory in multiple sclerosis. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for multiple sclerosis patients.

  13. Delphi definition of the EADC-ADNI Harmonized Protocol for hippocampal segmentation on magnetic resonance.

    Science.gov (United States)

    Boccardi, Marina; Bocchetta, Martina; Apostolova, Liana G; Barnes, Josephine; Bartzokis, George; Corbetta, Gabriele; DeCarli, Charles; deToledo-Morrell, Leyla; Firbank, Michael; Ganzola, Rossana; Gerritsen, Lotte; Henneman, Wouter; Killiany, Ronald J; Malykhin, Nikolai; Pasqualetti, Patrizio; Pruessner, Jens C; Redolfi, Alberto; Robitaille, Nicolas; Soininen, Hilkka; Tolomeo, Daniele; Wang, Lei; Watson, Craig; Wolf, Henrike; Duvernoy, Henri; Duchesne, Simon; Jack, Clifford R; Frisoni, Giovanni B

    2015-02-01

    This study aimed to have international experts converge on a harmonized definition of whole hippocampus boundaries and segmentation procedures, to define standard operating procedures for magnetic resonance (MR)-based manual hippocampal segmentation. The panel received a questionnaire regarding whole hippocampus boundaries and segmentation procedures. Quantitative information was supplied to allow evidence-based answers. A recursive and anonymous Delphi procedure was used to achieve convergence. Significance of agreement among panelists was assessed by exact probability on Fisher's and binomial tests. Agreement was significant on the inclusion of alveus/fimbria (P = .021), whole hippocampal tail (P = .013), medial border of the body according to visible morphology (P = .0006), and on this combined set of features (P = .001). This definition captures 100% of hippocampal tissue, 100% of Alzheimer's disease-related atrophy, and demonstrated good reliability on preliminary intrarater (0.98) and inter-rater (0.94) estimates. Consensus was achieved among international experts with respect to hippocampal segmentation using MR resulting in a harmonized segmentation protocol. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  14. MRI segmentation in the diagnosis and clinical correlations of temporal lobe epilepsy

    International Nuclear Information System (INIS)

    He Huijin; Shen Tianzhen; Chen Xingrong; Feng Xiaoyuan; Jiang Chengchuan

    2004-01-01

    Objective: To study the different patterns of hippocampal atrophy by MRI segmental analysis and to investigate the etiology and pathogenesis of temporal lobe epilepsy. Methods: GE 1.5 T Signa Horizon LX MRI scanner was used. Oblique coronal T 1 weighted images perpendicular to the long axis of the hippocampus were obtained. The mesial temporal structures were divided into four parts: the amygdala, hippocampal head, body and tail. MRI patterns of atrophy in 50 patients with histologically confirmed hippocampal sclerosis were investigated by MRI volumetric measurement and segmental analysis, and the differences of clinical features and surgical outcome in different groups were compared. Results: Diffuse hippocampal atrophy was found in 22 of 50 patients (44%), 5 of the 50 patients (10%) showed diffuse atrophy involving both the amygdala and hippocampus. 20 of the 50 patients (40%) had hippocampal focal atrophy and 8 of 50 patients (16%) had no obvious atrophy. 38 of 50 (76%) hippocampal sclerosis had atrophy in the hippocampal body, 29 of 50 (58%) had hippocampal head atrophy, 24 of 50 (48%) had hippocampal tail atrophy, and the least involved part was the amygdala (16%, 8/50). 10 patients who had normal hippocampal volume showed focal hippocampal atrophy by segmental analysis. Various patterns of hippocampal atrophy were found to be statistically related to the duration of epilepsy, the frequency of seizure and the outcome of surgery, respectively (P 0.05). Conclusion: MRI segmental analysis can improve the diagnostic sensitivity of temporal lobe epilepsy and help to investigate its etiology and pathogenesis. (author)

  15. The cumulative analgesic effect of repeated electroacupuncture involves synaptic remodeling in the hippocampal CA3 region☆

    Science.gov (United States)

    Xu, Qiuling; Liu, Tao; Chen, Shuping; Gao, Yonghui; Wang, Junying; Qiao, Lina; Liu, Junling

    2012-01-01

    In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanli (ST36) and Yanglingquan (GB34) once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold (paw withdrawal latency) was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptic cleft width and thinning of the postsynaptic density, and it significantly suppressed the down-regulation of intracellular calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. PMID:25657670

  16. Vaginal Atrophy

    Science.gov (United States)

    ... an Endocrinologist Search Featured Resource Menopause Map™ View Vaginal Atrophy October 2017 Download PDFs English Editors Christine ... during this time, including vaginal dryness. What is vaginal atrophy? Vaginal atrophy (also referred to as vulvovaginal ...

  17. Automated volumetry for unilateral hippocampal sclerosis detection in patients with temporal lobe epilepsy.

    Science.gov (United States)

    Martins, Cristina; Moreira da Silva, Nadia; Silva, Guilherme; Rozanski, Verena E; Silva Cunha, Joao Paulo

    2016-08-01

    Hippocampal sclerosis (HS) is the most common cause of temporal lobe epilepsy (TLE) and can be identified in magnetic resonance imaging as hippocampal atrophy and subsequent volume loss. Detecting this kind of abnormalities through simple radiological assessment could be difficult, even for experienced radiologists. For that reason, hippocampal volumetry is generally used to support this kind of diagnosis. Manual volumetry is the traditional approach but it is time consuming and requires the physician to be familiar with neuroimaging software tools. In this paper, we propose an automated method, written as a script that uses FSL-FIRST, to perform hippocampal segmentation and compute an index to quantify hippocampi asymmetry (HAI). We compared the automated detection of HS (left or right) based on the HAI with the agreement of two experts in a group of 19 patients and 15 controls, achieving 84.2% sensitivity, 86.7% specificity and a Cohen's kappa coefficient of 0.704. The proposed method is integrated in the "Advanced Brain Imaging Lab" (ABrIL) cloud neurocomputing platform. The automated procedure is 77% (on average) faster to compute vs. the manual volumetry segmentation performed by an experienced physician.

  18. Temporal Changes in Cortical and Hippocampal Expression of Genes Important for Brain Glucose Metabolism Following Controlled Cortical Impact Injury in Mice

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    June Zhou

    2017-09-01

    Full Text Available Traumatic brain injury (TBI causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group underwent sham or unilateral controlled cortical impact (CCI injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after injury. Expressions of several genes important for brain glucose utilization were determined by qRT-PCR. In results, (1 mRNA levels of three key enzymes in glucose metabolism [hexo kinase (HK 1, pyruvate kinase, and pyruvate dehydrogenase (PDH] were all increased 6 h after injury in the contralateral cortex, followed by decreases at subsequent times in the ipsilateral cortex and hippocampus; (2 capillary glucose transporter Glut-1 mRNA increased, while neuronal glucose transporter Glut-3 mRNA decreased, at various times in the ipsilateral cortex and hippocampus; (3 astrocyte lactate transporter MCT-1 mRNA increased, whereas neuronal lactate transporter MCT-2 mRNA decreased in the ipsilateral cortex and hippocampus; (4 HK2 (an isoform of hexokinase expression increased at all time points in the ipsilateral cortex and hippocampus. GPR81 (lactate receptor mRNA increased at various time points in the ipsilateral cortex and hippocampus. These temporal alterations in gene expression corresponded closely to the patterns of impaired brain glucose utilization reported in both TBI patients and experimental TBI rodents. The observed changes in hippocampal gene expression were delayed and prolonged, when compared with those in the cortex. The patterns of alterations were specific

  19. Midlife managerial experience is linked to late life hippocampal morphology and function.

    Science.gov (United States)

    Suo, C; Gates, N; Fiatarone Singh, M; Saigal, N; Wilson, G C; Meiklejohn, J; Sachdev, P; Brodaty, H; Wen, W; Singh, N; Baune, B T; Baker, M; Foroughi, N; Wang, Y; Valenzuela, Michael J

    2017-04-01

    An active cognitive lifestyle has been suggested to have a protective role in the long-term maintenance of cognition. Amongst healthy older adults, more managerial or supervisory experiences in midlife are linked to a slower hippocampal atrophy rate in late life. Yet whether similar links exist in individuals with Mild Cognitive Impairment (MCI) is not known, nor whether these differences have any functional implications. 68 volunteers from the Sydney SMART Trial, diagnosed with non-amnestic MCI, were divided into high and low managerial experience (HME/LME) during their working life. All participants underwent neuropsychological testing, structural and resting-state functional MRI. Group comparisons were performed on hippocampal volume, morphology, hippocampal seed-based functional connectivity, memory and executive function and self-ratings of memory proficiency. HME was linked to better memory function (p = 0.024), mediated by larger hippocampal volume (p = 0.025). More specifically, deformation analysis found HME had relatively more volume in the CA1 sub-region of the hippocampus (p < 0.05). Paradoxically, this group rated their memory proficiency worse (p = 0.004), a result correlated with diminished functional connectivity between the right hippocampus and right prefrontal cortex (p < 0.001). Finally, hierarchical regression modelling substantiated this double dissociation.

  20. Progressive hemifacial atrophy with ciliary body atrophy and ocular hypotony

    Directory of Open Access Journals (Sweden)

    T Ashwini Kini

    2015-01-01

    Full Text Available Progressive hemifacial atrophy (PHA is a disease of unknown etiology affecting one-half of the face. Ocular involvement is uncommon. Atrophy of iris is rare, with only a few cases of partial atrophy being reported in the literature. We report a case of total atrophy of iris and ciliary body with associated ocular hypotony in a 16-year-old girl with PHA. We believe this is the first reported case of complete atrophy of iris and ciliary body in PHA. Ocular hypotony in PHA was thought to be due to intra-ocular inflammation. However in our case it appears to be secondary to severe atrophy of the ciliary body.

  1. Roles of hippocampal subfields in verbal and visual episodic memory.

    Science.gov (United States)

    Zammit, Andrea R; Ezzati, Ali; Zimmerman, Molly E; Lipton, Richard B; Lipton, Michael L; Katz, Mindy J

    2017-01-15

    Selective hippocampal (HC) subfield atrophy has been reported in older adults with mild cognitive impairment and Alzheimer's disease. The goal of this study was to investigate the associations between the volume of hippocampal subfields and visual and verbal episodic memory in cognitively normal older adults. This study was conducted on a subset of 133 participants from the Einstein Aging Study (EAS), a community-based study of non-demented older adults systematically recruited from the Bronx, N.Y. All participants completed comprehensive EAS neuropsychological assessment. Visual episodic memory was assessed using the Complex Figure Delayed Recall subtest from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Verbal episodic memory was assessed using Delayed Recall from the Free and Cued Selective Reminding Test (FCSRT). All participants underwent 3T MRI brain scanning with subsequent automatic measurement of the hemispheric hippocampal subfield volumes (CA1, CA2-CA3, CA4-dente gyrus, presubiculum, and subiculum). We used linear regressions to model the association between hippocampal subfield volumes and visual and verbal episodic memory tests while adjusting for age, sex, education, and total intracranial volume. Participants had a mean age of 78.9 (SD=5.1) and 60.2% were female. Total hippocampal volume was associated with Complex Figure Delayed Recall (β=0.31, p=0.001) and FCSRT Delayed Recall (β=0.27, p=0.007); subiculum volume was associated with Complex Figure Delayed Recall (β=0.27, p=0.002) and FCSRT Delayed Recall (β=0.24, p=0.010); CA1 was associated with Complex Figure Delayed Recall (β=0.26, pepisodic memory. Our results suggest that hippocampal subfields have sensitive roles in the process of visual and verbal episodic memory. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

    NARCIS (Netherlands)

    Papma, Janne M.; Smits, Marion; De Groot, Marius; Mattace-Raso, Francesco U. S.; van der Lugt, Aad; Vrooman, Henri A.; Niessen, W.J.; Koudstaal, Peter J.; van Swieten, John C.; van der Veen, Frederik M.; Prins, Niels D.

    2017-01-01

    Objectives: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the

  3. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

    NARCIS (Netherlands)

    J.M. Papma (Janne); M. Smits (Marion); M. de Groot (Mirthe); F.U.S. Mattace Raso (Francesco); A. van der Lugt (Aad); H.A. Vrooman (Henri); W.J. Niessen (Wiro); P.J. Koudstaal (Peter Jan); J.C. van Swieten (John); F.M. van der Veen (Frederik); N.D. Prins (Niels)

    2017-01-01

    textabstractObjectives: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the

  4. Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury

    Science.gov (United States)

    Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

    2018-01-01

    Abstract Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the

  5. Hippocampal sclerosis and status epilepticus: cause or consequence? A MRI study; Esclerose hipocampal e status epilepticus: causa ou consequencia? Um estudo de RM

    Energy Technology Data Exchange (ETDEWEB)

    Kuster, Gustavo Wruck; Braga-Neto, Pedro; Santos-Neto, Denizart; Santana, Maria Teresa Garcia; Barsottini, Orlando Graziani [Universidade Federal de Sao Paulo (UNIFESP-EPM), Sao Paulo, SP (Brazil). Dept. of Neurology. Div. of General Neurology; Maia Junior, Antonio Carlos Martins [Fleury Institute, Sao Paulo, SP (Brazil). Magnetic Resonance Imaging Unit

    2007-12-15

    Background: Transient imaging abnormalities, including changes on diffusion-weighted imaging (DWI), may be seen in status epilepticus. These abnormalities can be followed by hippocampal sclerosis. Case Report: We report a 15-year-old lady with focal non convulsive status epilepticus (NCSE) and focal slowing on EEG. DWI exhibited abnormal hyperintense signals in bilateral temporal and insular cortices. After 3 weeks, MRI performed a localized hippocampal atrophy. Conclusion: The MRI findings indicated vasogenic and cytotoxic edema during seizure activity and subsequent loss of brain parenchyma. (author)

  6. Atrophy and Primary Somatosensory Cortical Reorganization after Unilateral Thoracic Spinal Cord Injury: A Longitudinal Functional Magnetic Resonance Imaging Study

    Directory of Open Access Journals (Sweden)

    Jia-Sheng Rao

    2013-01-01

    Full Text Available The effects of traumatic spinal cord injury (SCI on the changes in the central nervous system (CNS over time may depend on the dynamic interaction between the structural integrity of the spinal cord and the capacity of the brain plasticity. Functional magnetic resonance imaging (fMRI was used in a longitudinal study on five rhesus monkeys to observe cerebral activation during upper limb somatosensory tasks in healthy animals and after unilateral thoracic SCI. The changes in the spinal cord diameters were measured, and the correlations among time after the lesion, structural changes in the spinal cord, and primary somatosensory cortex (S1 reorganization were also determined. After SCI, activation of the upper limb in S1 shifted to the region which generally dominates the lower limb, and the rostral spinal cord transverse diameter adjacent to the lesion exhibited obvious atrophy, which reflects the SCI-induced changes in the CNS. A significant correlation was found among the time after the lesion, the spinal cord atrophy, and the degree of contralateral S1 reorganization. The results indicate the structural changes in the spinal cord and the dynamic reorganization of the cerebral activation following early SCI stage, which may help to further understand the neural plasticity in the CNS.

  7. Hippocampal Volumetry as a Biomarker for Dementia in People with Low Education.

    Science.gov (United States)

    Mondragón, Jaime D; Celada-Borja, César; Barinagarrementeria-Aldatz, Fernando; Burgos-Jaramillo, Martín; Barragán-Campos, Héctor Manuel

    2016-01-01

    To evaluate the relationship between hippocampal volume and cognitive decline in patients with dementia due to probable Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI) and education, and the possible relationship between cognitive reserve and education in this population. From February 2013 to October 2015, 76 patients (25 men, 51 women) were classified according to the NIA-AA diagnostic criteria. We used two 3.0-tesla MRI scanners and performed manual hippocampal volumetry. Twenty-six patients were found to have AD, 20 aMCI and 30 had normal aging (NA). The mean normalized hippocampal volume in age-, sex- and education (years)-matched subjects was 2.38 ± 0.51 cm 3 in AD (p < 0.001), 2.91 ± 0.78 cm 3 in aMCI (p = 0.019) and 3.07 ± 0.76 cm 3 in NA. Psychometric test (MMSE and MoCA) scores had a good to strong positive correlation with statistically significant differences in the entire population and healthy subjects but not among dementia patients and lower educational level groups. The patients with low education had greater hippocampal volumes, which is in line with the cognitive reserve theory; lower-educated individuals can tolerate less neuropathology and will thus show less atrophy at a similar level of cognitive performance than higher-educated subjects.

  8. Low-intensity daily walking activity is associated with hippocampal volume in older adults.

    Science.gov (United States)

    Varma, Vijay R; Chuang, Yi-Fang; Harris, Gregory C; Tan, Erwin J; Carlson, Michelle C

    2015-05-01

    Hippocampal atrophy is associated with memory impairment and dementia and serves as a key biomarker in the preclinical stages of Alzheimer's disease. Physical activity, one of the most promising behavioral interventions to prevent or delay cognitive decline, has been shown to be associated with hippocampal volume; specifically increased aerobic activity and fitness may have a positive effect on the size of the hippocampus. The majority of older adults, however, are sedentary and have difficulty initiating and maintaining exercise programs. A modestly more active lifestyle may nonetheless be beneficial. This study explored whether greater objectively measured daily walking activity was associated with larger hippocampal volume. We additionally explored whether greater low-intensity walking activity, which may be related to leisure-time physical, functional, and social activities, was associated with larger hippocampal volume independent of exercise and higher-intensity walking activity. Segmentation of hippocampal volumes was performed using Functional Magnetic Resonance Imaging of the Brain's Software Library (FSL), and daily walking activity was assessed using a step activity monitor on 92, nondemented, older adult participants. After controlling for age, education, body mass index, cardiovascular disease risk factors, and the Mini Mental State Exam, we found that a greater amount, duration, and frequency of total daily walking activity were each associated with larger hippocampal volume among older women, but not among men. These relationships were specific to hippocampal volume, compared with the thalamus, used as a control brain region, and remained significant for low-intensity walking activity, independent of moderate- to vigorous-intensity activity and self-reported exercise. This is the first study, to our knowledge, to explore the relationship between objectively measured daily walking activity and hippocampal volume in an older adult population. Findings

  9. Quantitative MRI study of progressive cerebral atrophy in multiple system atrophy

    International Nuclear Information System (INIS)

    Konagaya, Masaaki; Matsuoka, Yukihiko; Konagaya, Yoko

    2002-01-01

    We investigated cerebral atrophy in multiple system atrophy (MSA) by quantitative analysis of MRI. The subjects were 28 patients with MSA (14 striato-nigral degeneration; SND, 14 olivo-ponto-cerebellar atrophy; OPCA. 106 MRI examinations were performed totally) and 85 normal persons for control. The ratios of the ventral pons to the infratentorial space in the sagittal section, the putamen, cerebrum, frontal lobe and parietal and occipital lobes to the intracranial space in the horizontal section, and the temporal lobe to the intracranial space in the coronal section were measured. In the early stage of the disease, OPCA showed significant atrophy of the ventral pons compared with SND, and conversely, SND demonstrated significantly smaller putamen than that in OPCA. According to the progression of the disease, the atrophy of these neural tissues progressed, which resulted in so significant differences between SND and OPCA. The cerebral atrophy was observed in 17 MSA patients. The atrophy of the frontal lobe was much frequent and prominent to that in the temporal lobe and parietal and occipital lobes. SND showed higher incidence of the cerebral atrophy than OPCA in the early stage of the disease. In long period follow-up cases, one case showed cerebral atrophy in earlier stage, and another case in late stage. We indicated the involvement of the cerebral hemispheres in MSA, especially the frontal lobe. (author)

  10. Quantitative MRI study of progressive cerebral atrophy in multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Konagaya, Masaaki; Matsuoka, Yukihiko [Suzuka National Hospital, Suzuka, Mie (Japan); Konagaya, Yoko [JR Tokai General Hospital, Nagoya (Japan)

    2002-02-01

    We investigated cerebral atrophy in multiple system atrophy (MSA) by quantitative analysis of MRI. The subjects were 28 patients with MSA (14 striato-nigral degeneration; SND, 14 olivo-ponto-cerebellar atrophy; OPCA. 106 MRI examinations were performed totally) and 85 normal persons for control. The ratios of the ventral pons to the infratentorial space in the sagittal section, the putamen, cerebrum, frontal lobe and parietal and occipital lobes to the intracranial space in the horizontal section, and the temporal lobe to the intracranial space in the coronal section were measured. In the early stage of the disease, OPCA showed significant atrophy of the ventral pons compared with SND, and conversely, SND demonstrated significantly smaller putamen than that in OPCA. According to the progression of the disease, the atrophy of these neural tissues progressed, which resulted in so significant differences between SND and OPCA. The cerebral atrophy was observed in 17 MSA patients. The atrophy of the frontal lobe was much frequent and prominent to that in the temporal lobe and parietal and occipital lobes. SND showed higher incidence of the cerebral atrophy than OPCA in the early stage of the disease. In long period follow-up cases, one case showed cerebral atrophy in earlier stage, and another case in late stage. We indicated the involvement of the cerebral hemispheres in MSA, especially the frontal lobe. (author)

  11. Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury.

    Science.gov (United States)

    Cole, James H; Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

    2018-01-04

    Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the follow

  12. Beyond dizziness: virtual navigation, spatial anxiety and hippocampal volume in bilateral vestibulopathy

    Directory of Open Access Journals (Sweden)

    Olympia eKremmyda

    2016-03-01

    Full Text Available Bilateral vestibulopathy (BVP is defined as the impairment or loss of function of either the labyrinths or the eighth nerves. Patients with total BVP due to bilateral vestibular nerve section exhibit difficulties in spatial memory and navigation and show a loss of hippocampal volume. In clinical practice, most patients do not have a complete loss of function but rather an asymmetrical residual functioning of the vestibular system. The purpose of the current study was to investigate navigational ability and hippocampal atrophy in BVP patients with residual vestibular function. Fifteen patients with BVP and a group of age- and gender- matched healthy controls were examined. Self-reported questionnaires on spatial anxiety and wayfinding were used to assess the applied strategy of wayfinding and quality of life. Spatial memory and navigation were tested directly using a virtual Morris Water Maze Task. The hippocampal volume of these two groups was evaluated by voxel-based morphometry. In the patients, the questionnaire showed a higher spatial anxiety and the Morris Water Maze Task a delayed spatial learning performance. MRI revealed a significant decrease in the gray matter mid-hippocampal volume (Left: p = 0.006, Z = 4.58, Right: p < 0.001, Z = 3.63 and posterior parahippocampal volume (Right: p = 0.005, Z = 4.65, Left: p < 0.001, Z = 3.87 compared to those of healthy controls. In addition, a decrease in hippocampal formation volume correlated with a more dominant route-finding strategy. Our current findings demonstrate that even partial bilateral vestibular loss leads to anatomical and functional

  13. Ipsilateral hippocampal atrophy is associated with long-term memory dysfunction after ischemic stroke in young adults

    NARCIS (Netherlands)

    Schaapsmeerders, P.; Uden, I.W.M. van; Tuladhar, A.M.; Maaijwee, N.A.M.M.; Dijk, E.J. van; Rutten-Jacobs, L.C.A.; Arntz, R.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.A.; Leeuw, H.F. de; Kessels, R.P.C.

    2015-01-01

    Memory impairment after stroke in young adults is poorly understood. In elderly stroke survivors memory impairments and the concomitant loss of hippocampal volume are usually explained by coexisting neurodegenerative disease (e.g., amyloid pathology) in interaction with stroke. However,

  14. Preoperative MR imaging-based volume measurements of the hippocampal formation and anterior temporal lobe in epileptic patients

    International Nuclear Information System (INIS)

    Jack, C.R.; Sharbrough, F.W.; Twomey, C.; Zinsmeister, A.R.; Cascino, G.D.; Hirschorn, K.A.; Marsh, W.R.

    1989-01-01

    MR-based volume measurements of the anterior temporal lobe and hippocampal formation were performed in 36 patients who subsequently underwent surgery for medically refractory temporal lobe epilepsy. Seizure lateralization was based on standard clinical and electroencephalographic criteria. No surgical pathologic specimens contained structural lesions; epilepsy in these patients was therefore presumably due to mesial sclerosis. The right-minus-left hippocampal formation volume difference was greater than 0 in all 20 patients operated on the left side and less than 0 in all 16 patients operated on the right side. This difference completely separated the two surgical groups, while the same measurement in a group of 35 normal controls fell between the two surgical groups. Measurements of the anterior temporal to be showed a similar trend but incompletely separated controls, right- and left-sided epileptics. These results suggest that in a significant percentage of cases, MR-based volume measurements correctly identify the unilateral hippocampal atrophy that is known to occur in cases of mesial temporal sclerosis

  15. Memory Dysfunction in Type 2 Diabetes Mellitus Correlates with Reduced Hippocampal CA1 and Subiculum Volumes

    Directory of Open Access Journals (Sweden)

    Yan-Wei Zhang

    2015-01-01

    Full Text Available Background: Little attention has been paid to the role of subcortical deep gray matter (SDGM structures in type 2 diabetes mellitus (T2DM-induced cognitive impairment, especially hippocampal subfields. Our aims were to assess the in vivo volumes of SDGM structures and hippocampal subfields using magnetic resonance imaging (MRI and to test their associations with cognitive performance in T2DM. Methods: A total of 80 T2DM patients and 80 neurologically unimpaired healthy controls matched by age, sex and education level was enrolled in this study. We assessed the volumes of the SDGM structures and seven hippocampal subfields on MRI using a novel technique that enabled automated volumetry. We used Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA scores as measures of cognitive performance. The association of glycosylated hemoglobin (HbA1c with SDGM structures and neuropsychological tests and correlations between hippocampal subfields and neuropsychological tests were assessed by partial correlation analysis in T2DM. Results: Bilaterally, the hippocampal volumes were smaller in T2DM patients, mainly in the CA1 and subiculum subfields. Partial correlation analysis showed that the MoCA scores, particularly those regarding delayed memory, were significantly positively correlated with reduced hippocampal CA1 and subiculum volumes in T2DM patients. Additionally, higher HbA1c levels were significantly associated with poor memory performance and hippocampal atrophy among T2DM patients. Conclusions: These data indicate that the hippocampus might be the main affected region among the SDGM structures in T2DM. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction, suggesting that degeneration in these regions could be responsible for memory impairments in T2DM patients.

  16. Brain atrophy during aging

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju; Yamada, Kenji; Yamada, Susumu; Ono, Shuichi; Takeda, Shunpei; Hatazawa, Jun; Ito, Masatoshi; Kubota, Kazuo

    1985-01-01

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT. Brain atrophy was minimal in 34-35 years old in both sexes, increased exponentially to the increasing age after 34-35 years, and probably resulted in dementia, such as vascular or multi-infarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34-35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extent of brain atrophy (20 - 30 %) existed among aged subjects. Progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was the decrease in the cerebral blood flow. We have classified brain atrophy into sulcal and cisternal enlargement type (type I), ventricular enlargement type (type II) and mixed type (type III) according to the clinical study using NMR-CT. Brain atrophy of type I progresses significantly in almost all of the geriatric disorders. This type of brain atrophy progresses significantly in heavy smokers and drinkers. Therefore this type of brain atrophy might be caused by the decline in the blood flow in anterior and middle cerebral arteries. Brain atrophy of type II was caused by the disturbance of cerebrospinal fluid circulation after cerebral bleeding and subarachnoid bleeding. Brain atrophy of type III was seen in vascular dementia or multi-infarct dementia which was caused by loss of brain matter after multiple infarction, and was seen also in dementia of Alzheimer type in which degeneration of nerve cells results in brain atrophy. NMR-CT can easily detect small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy. (J.P.N.)

  17. Induction of the Wnt antagonist Dickkopf-1 is involved in stress-induced hippocampal damage.

    Directory of Open Access Journals (Sweden)

    Francesco Matrisciano

    Full Text Available The identification of mechanisms that mediate stress-induced hippocampal damage may shed new light into the pathophysiology of depressive disorders and provide new targets for therapeutic intervention. We focused on the secreted glycoprotein Dickkopf-1 (Dkk-1, an inhibitor of the canonical Wnt pathway, involved in neurodegeneration. Mice exposed to mild restraint stress showed increased hippocampal levels of Dkk-1 and reduced expression of β-catenin, an intracellular protein positively regulated by the canonical Wnt signalling pathway. In adrenalectomized mice, Dkk-1 was induced by corticosterone injection, but not by exposure to stress. Corticosterone also induced Dkk-1 in mouse organotypic hippocampal cultures and primary cultures of hippocampal neurons and, at least in the latter model, the action of corticosterone was reversed by the type-2 glucocorticoid receptor antagonist mifepristone. To examine whether induction of Dkk-1 was causally related to stress-induced hippocampal damage, we used doubleridge mice, which are characterized by a defective induction of Dkk-1. As compared to control mice, doubleridge mice showed a paradoxical increase in basal hippocampal Dkk-1 levels, but no Dkk-1 induction in response to stress. In contrast, stress reduced Dkk-1 levels in doubleridge mice. In control mice, chronic stress induced a reduction in hippocampal volume associated with neuronal loss and dendritic atrophy in the CA1 region, and a reduced neurogenesis in the dentate gyrus. Doubleridge mice were resistant to the detrimental effect of chronic stress and, instead, responded to stress with increases in dendritic arborisation and neurogenesis. Thus, the outcome of chronic stress was tightly related to changes in Dkk-1 expression in the hippocampus. These data indicate that induction of Dkk-1 is causally related to stress-induced hippocampal damage and provide the first evidence that Dkk-1 expression is regulated by corticosteroids in the central

  18. Genetic influence of apolipoprotein E4 genotype on hippocampal morphometry: An N = 725 surface-based Alzheimer's disease neuroimaging initiative study.

    Science.gov (United States)

    Shi, Jie; Leporé, Natasha; Gutman, Boris A; Thompson, Paul M; Baxter, Leslie C; Caselli, Richard J; Wang, Yalin

    2014-08-01

    The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer's disease (AD). Hippocampal volumes are generally smaller in AD patients carrying the e4 allele compared to e4 noncarriers. Here we examined the effect of APOE e4 on hippocampal morphometry in a large imaging database-the Alzheimer's Disease Neuroimaging Initiative (ADNI). We automatically segmented and constructed hippocampal surfaces from the baseline MR images of 725 subjects with known APOE genotype information including 167 with AD, 354 with mild cognitive impairment (MCI), and 204 normal controls. High-order correspondences between hippocampal surfaces were enforced across subjects with a novel inverse consistent surface fluid registration method. Multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance were computed for surface deformation analysis. Using Hotelling's T(2) test, we found significant morphological deformation in APOE e4 carriers relative to noncarriers in the entire cohort as well as in the nondemented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes. Our findings are consistent with previous studies that showed e4 carriers exhibit accelerated hippocampal atrophy; we extend these findings to a novel measure of hippocampal morphometry. Hippocampal morphometry has significant potential as an imaging biomarker of early stage AD. Copyright © 2014 Wiley Periodicals, Inc.

  19. Bigger is better and worse: on the intricate relationship between hippocampal size and memory.

    Science.gov (United States)

    Molnár, Katalin; Kéri, Szabolcs

    2014-04-01

    The structure-function relationship between the hippocampal region and memory is a debated topic in the literature. It has been suggested that larger hippocampi are associated with less effective memory performance in healthy young adults because of a partial synaptic pruning. Here, we tested this hypothesis in individuals with Fragile X Syndrome (FXS) with known abnormal pruning and IQ- and age-matched individuals with hypoxic brain injury, preterm birth, and obstetric complications. Results revealed larger normalized hippocampal volume in FXS compared with neurotypical controls, whereas individuals with hypoxic injury had smaller hippocampi. In neurotypical controls and individuals with hypoxic injury, better general memory, as indexed by the Wechsler Memory Scale-Revised, was associated with larger hippocampus. In contrast, in FXS we observed the opposite relationship: larger hippocampus was associated with worse general memory. Caudate volume did not correlate with memory in either group. These results suggest that incomplete pruning in young healthy adults may not contribute to less efficient memory capacity, and hippocampal size is positively associated with memory performance. However, abnormally large and poorly pruned hippocampus may indeed be less effective in FXS. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Neuroprotective effects of ginsenoside Rg1 against oxygen-glucose deprivation in cultured hippocampal neurons.

    Science.gov (United States)

    He, Qing; Sun, Jianguo; Wang, Qin; Wang, Wei; He, Bin

    2014-03-01

    Ginsenoside Rg1 (Rg1) is believed to be one of the main active principles in ginseng, a traditional Chinese medicine extensively used to enhance stamina and deal with fatigue as well as physical stress. It has been reported that Rg1 performs multiple biological activities, including neuroprotective activity. In this study, we investigated the efficacy of ginsenoside Rg1 on ischemia-reperfusion injury in cultured hippocampal cells and also probed its possible mechanisms. To establish a model of oxygen-glucose deprivation (OGD) and reperfusion, cultured hippocampal neurons were exposed to OGD for 2.5 hours, followed by a 24-hour reoxygenation. Cultured hippocampal neurons were randomly divided into control group, model group (vehicle), and ginsenoside Rg1 treatment groups (5μM, 20μM, 60μM). At 24 hours post-OGD, the intracellular free calcium concentration was detected using Furo-3/AM-loaded hippocampal neurons deprived of oxygen and glucose. Neuronal nitric oxide synthase (nNOS) activity was measured by chemical colorimetry. Cell apoptosis was evaluated by Hoechst staining, and the neuron viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Excitotoxic neuronal injury of OGD was demonstrated by the increase of intracellular free calcium concentrations and elevated nNOS activity in the model group compared with the control group. The intracellular free calcium concentrations and the nNOS activity in the groups receiving intermediate and high dose of ginsenoside Rg1 were significantly lower than those of the control group (p cell viability loss (p cell apoptosis induced by OGD. Ginsenoside Rg1 has neuroprotective effect on ischemia-reperfusion injury in cultured hippocampal cells mediated by blocking calcium over-influx into neuronal cells and decreasing the nNOS activity after OGD exposure. We infer that ginsenoside Rg1 may serve as a potential therapeutic agent for cerebral ischemia injury. Copyright © 2014

  1. Head injury in children

    International Nuclear Information System (INIS)

    Sugiura, Makoto; Mori, Nobuhiko; Yokosuka, Reiko; Yamamoto, Masaaki; Imanaga, Hirohisa

    1981-01-01

    Findings of computerized tomography (CT) in 183 cases of head injury in children were investigated with special reference to CT findings of mild head injury. As was expected, CT findings of mild head injury fell within the normal range, in almost all cases. However, abnormal findings were noticed in 4 out of 34 cases (12%) in acute stage and 7 out of 76 cases (9%) in chronic stage. They were 3 cases of localized low density area in acute stage and 6 cases of mild cerebral atrophy in chronic stage, etc. There were some cases of mild head injury in which CT findings were normal while EEG examination revealed abnormality. Also in some cases, x-ray study demonstrated linear skull fracture which CT failed to show. These conventional techniques could be still remained as useful adjunct aid in diagnosis of head injury. CT findings of cases of cerebral contusion in their acute stage were divided as follows; normal, low density, small ventricle and ventricular and/or cisternal hemorrhage, frequency of incidence being 38, 17, 22, 11% respectively. These findings were invariably converted to cerebral atrophy from 10 days to 2 months after the impacts. In the cases with intracranial hematoma revealed by CT, only 32% of them showed clinical signs of Araki's type IV in their acute stage and 63% of them showed no neurological defects, that is Araki's type I and II. A case of extreme diffuse cerebral atrophy which followed acute subdural hematoma caused by tear of bridging veins without cortical contusion was presented. (author)

  2. Interleukin-1 Receptor in Seizure Susceptibility after Traumatic Injury to the Pediatric Brain.

    Science.gov (United States)

    Semple, Bridgette D; O'Brien, Terence J; Gimlin, Kayleen; Wright, David K; Kim, Shi Eun; Casillas-Espinosa, Pablo M; Webster, Kyria M; Petrou, Steven; Noble-Haeusslein, Linda J

    2017-08-16

    Epilepsy after pediatric traumatic brain injury (TBI) is associated with poor quality of life. This study aimed to characterize post-traumatic epilepsy in a mouse model of pediatric brain injury, and to evaluate the role of interleukin-1 (IL-1) signaling as a target for pharmacological intervention. Male mice received a controlled cortical impact or sham surgery at postnatal day 21, approximating a toddler-aged child. Mice were treated acutely with an IL-1 receptor antagonist (IL-1Ra; 100 mg/kg, s.c.) or vehicle. Spontaneous and evoked seizures were evaluated from video-EEG recordings. Behavioral assays tested for functional outcomes, postmortem analyses assessed neuropathology, and brain atrophy was detected by ex vivo magnetic resonance imaging. At 2 weeks and 3 months post-injury, TBI mice showed an elevated seizure response to the convulsant pentylenetetrazol compared with sham mice, associated with abnormal hippocampal mossy fiber sprouting. A robust increase in IL-1β and IL-1 receptor were detected after TBI. IL-1Ra treatment reduced seizure susceptibility 2 weeks after TBI compared with vehicle, and a reduction in hippocampal astrogliosis. In a chronic study, IL-1Ra-TBI mice showed improved spatial memory at 4 months post-injury. At 5 months, most TBI mice exhibited spontaneous seizures during a 7 d video-EEG recording period. At 6 months, IL-1Ra-TBI mice had fewer evoked seizures compared with vehicle controls, coinciding with greater preservation of cortical tissue. Findings demonstrate this model's utility to delineate mechanisms underlying epileptogenesis after pediatric brain injury, and provide evidence of IL-1 signaling as a mediator of post-traumatic astrogliosis and seizure susceptibility. SIGNIFICANCE STATEMENT Epilepsy is a common cause of morbidity after traumatic brain injury in early childhood. However, a limited understanding of how epilepsy develops, particularly in the immature brain, likely contributes to the lack of efficacious treatments

  3. Multifidus Muscle Changes After Back Injury Are Characterized by Structural Remodeling of Muscle, Adipose and Connective Tissue, but Not Muscle Atrophy: Molecular and Morphological Evidence.

    Science.gov (United States)

    Hodges, Paul W; James, Gregory; Blomster, Linda; Hall, Leanne; Schmid, Annina; Shu, Cindy; Little, Chris; Melrose, James

    2015-07-15

    Longitudinal case-controlled animal study. To investigate putative cellular mechanisms to explain structural changes in muscle and adipose and connective tissues of the back muscles after intervertebral disc (IVD) injury. Structural back muscle changes are ubiquitous with back pain/injury and considered relevant for outcome, but their exact nature, time course, and cellular mechanisms remain elusive. We used an animal model that produces phenotypic back muscle changes after IVD injury to study these issues at the cellular/molecular level. Multifidus muscle was harvested from both sides of the spine at L1-L2 and L3-L4 IVDs in 27 castrated male sheep at 3 (n = 10) or 6 (n = 17) months after a surgical anterolateral IVD injury at both levels. Ten control sheep underwent no surgery (3 mo, n = 4; 6 mo, n = 6). Tissue was harvested at L4 for histological analysis of cross-sectional area of muscle and adipose and connective tissue (whole muscle), plus immunohistochemistry to identify proportion and cross-sectional area of individual muscle fiber types in the deepest fascicle. Quantitative polymerase chain reaction measured gene expression of typical cytokines/signaling molecules at L2. Contrary to predictions, there was no multifidus muscle atrophy (whole muscle or individual fiber). There was increased adipose and connective tissue (fibrotic proliferation) cross-sectional area and slow-to-fast muscle fiber transition at 6 but not 3 months. Within the multifidus muscle, increases in the expression of several cytokines (tumor necrosis factor α and interleukin-1β) and molecules that signal trophic/atrophic processes for the 3 tissue types (e.g., growth factor pathway [IGF-1, PI3k, Akt1, mTOR], potent tissue modifiers [calcineurin, PCG-1α, and myostatin]) were present. This study provides cellular evidence that refutes the presence of multifidus muscle atrophy accompanying IVD degeneration at this intermediate time point. Instead, adipose/connective tissue increased in

  4. Neuroprotective effect of curcumin on hippocampal injury in 6-OHDA-induced Parkinson's disease rat.

    Science.gov (United States)

    Yang, Jiaqing; Song, Shilei; Li, Jian; Liang, Tao

    2014-06-01

    Clinically, Parkinson's disease (PD)-related neuronal lesions commonly occur. The purpose of this study is to investigate potential therapeutic effect of curcumin against hippocampal damage of 6-hydroxydopamine (6-OHDA)-PD rat model. These results showed that curcumin significantly increased the body weight of 6-OHDA-impaired rats (Pcurcumin-treated PD rats were effectively ameliorated as shown in open field test (Pcurcumin increased the contents of monoaminergic neurotransmitters (PCurcumin effectively alleviated the 6-OHDA-induced hippocampal damage as observed in hematoxylin-eosin (H&E) staining. Furthermore, curcumin obviously up-regulated hippocampal brain derived neurotrophic factor (BDNF), TrkB, phosphatidylinositide 3-kinases (PI3K) protein expressions, respectively as shown in Western blot analysis. These findings demonstrated that curcumin mediated the neuroprotection against 6-OHDA-induced hippocampus neurons in rats, which the underlying mechanism is involved in activating BDNF/TrkB-dependent pathway for promoting neural regeneration of hippocampal tissue. Copyright © 2014 Elsevier GmbH. All rights reserved.

  5. MicroRNA-132 protects hippocampal neurons against oxygen-glucose deprivation-induced apoptosis.

    Science.gov (United States)

    Sun, Zu-Zhen; Lv, Zhan-Yun; Tian, Wen-Jing; Yang, Yan

    2017-09-01

    Hypoxic-ischemic brain injury (HIBI) results in death or long-term neurologic impairment in both adults and children. In this study, we investigated the effects of microRNA-132 (miR-132) dysregulation on oxygen-glucose deprivation (OGD)-induced apoptosis in fetal rat hippocampal neurons, in order to reveal the therapeutic potential of miR-132 on HIBI. MiR-132 dysregulation was induced prior to OGD exposure by transfection of primary fetal rat hippocampal neurons with miR-132 mimic or miR-132 inhibitor. The effects of miR-132 overexpression and suppression on OGD-stimulated hippocampal neurons were evaluated by detection of cell viability, apoptotic cells rate, and the expression of apoptosis-related proteins. Besides, TargetScan database and dual luciferase activity assay were used to seek a target gene of miR-132. As a result, miR-132 was highly expressed in hippocampal neurons following 2 h of OGD exposure. MiR-132 overexpression significantly increased OGD-diminished cell viability and reduced OGD-induced apoptosis at 12, 24, and 48 h post-OGD. MiR-132 overexpression significantly down-regulated the expressions of Bax, cytochrome c, and caspase-9, but up-regulated BCl-2. Caspase-3 activity was also significantly decreased by miR-132 overexpression. Furthermore, FOXO3 was a direct target of miR-132, and it was negatively regulated by miR-132. To conclude, our results provide evidence that miR-132 protects hippocampal neurons against OGD injury by inhibiting apoptosis.

  6. Systematic comparison of different techniques to measure hippocampal subfield volumes in ADNI2

    DEFF Research Database (Denmark)

    Mueller, Susanne G.; Yushkevich, Paul A.; Das, Sandhitsu

    2018-01-01

    regression analyses were used to calculate effect sizes (ES) for group, amyloid positivity in controls, and associations with cognitive/memory performance for each approach. Results Subfield volumetry was better than whole hippocampal volumetry for the detection of the mild atrophy differences between...... and T1 subfield approaches. None of the different T2-HghRes methods tested had a clear advantage over the other methods. Each has strengths and weaknesses that need to be taken into account when deciding which one to use to get the best results from subfield volumetry....

  7. Subregional Hippocampal Morphology and Psychiatric Outcome in Adolescents Who Were Born Very Preterm and at Term.

    Directory of Open Access Journals (Sweden)

    James H Cole

    Full Text Available The hippocampus has been reported to be structurally and functionally altered as a sequel of very preterm birth (<33 weeks gestation, possibly due its vulnerability to hypoxic-ischemic damage in the neonatal period. We examined hippocampal volumes and subregional morphology in very preterm born individuals in mid- and late adolescence and their association with psychiatric outcome.Structural brain magnetic resonance images were acquired at two time points (baseline and follow-up from 65 ex-preterm adolescents (mean age = 15.5 and 19.6 years and 36 term-born controls (mean age=15.0 and 19.0 years. Hippocampal volumes and subregional morphometric differences were measured from manual tracings and with three-dimensional shape analysis. Psychiatric outcome was assessed with the Rutter Parents' Scale at baseline, the General Health Questionnaire at follow-up and the Peters Delusional Inventory at both time points.In contrast to previous studies we did not find significant difference in the cross-sectional or longitudinal hippocampal volumes between individuals born preterm and controls, despite preterm individual having significantly smaller whole brain volumes. Shape analysis at baseline revealed subregional deformations in 28% of total bilateral hippocampal surface, reflecting atrophy, in ex-preterm individuals compared to controls, and in 22% at follow-up. In ex-preterm individuals, longitudinal changes in hippocampal shape accounted for 11% of the total surface, while in controls they reached 20%. In the whole sample (both groups larger right hippocampal volume and bilateral anterior surface deformations at baseline were associated with delusional ideation scores at follow-up.This study suggests a dynamic association between cross-sectional hippocampal volumes, longitudinal changes and surface deformations and psychosis proneness.

  8. Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation.

    Science.gov (United States)

    Guderian, Sebastian; Dzieciol, Anna M; Gadian, David G; Jentschke, Sebastian; Doeller, Christian F; Burgess, Neil; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2015-10-21

    The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is

  9. Neuroprotective effects of ginsenoside Rg1 against oxygen–glucose deprivation in cultured hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Qing He

    2014-03-01

    Conclusion: Ginsenoside Rg1 has neuroprotective effect on ischemia–reperfusion injury in cultured hippocampal cells mediated by blocking calcium over-influx into neuronal cells and decreasing the nNOS activity after OGD exposure. We infer that ginsenoside Rg1 may serve as a potential therapeutic agent for cerebral ischemia injury.

  10. Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl phthalate in male Long Evans rats.

    Directory of Open Access Journals (Sweden)

    Catherine A Smith

    Full Text Available Early developmental exposure to di(2-ethylhexyl phthalate (DEHP has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats.

  11. Restoration of hippocampal growth hormone reverses stress-induced hippocampal impairment

    Directory of Open Access Journals (Sweden)

    Caitlin M. Vander Weele

    2013-06-01

    Full Text Available Though growth hormone (GH is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsal hippocampus via viral-mediated gene transfer completely reversed stress-related impairment of two hippocampus-dependent behavioral tasks, auditory trace fear conditioning and contextual fear conditioning, without affecting hippocampal function in unstressed control rats. GH overexpression reversed stress-induced decrements in both fear acquisition and long-term fear memory. These results suggest that loss of hippocampal GH contributes to hippocampal dysfunction following prolonged stress and demonstrate that restoring hippocampal GH levels following stress can promote stress resilience.

  12. Joint assessment of white matter integrity, cortical and subcortical atrophy to distinguish AD from behavioral variant FTD: A two-center study

    Directory of Open Access Journals (Sweden)

    Christiane Möller

    2015-01-01

    Full Text Available We investigated the ability of cortical and subcortical gray matter (GM atrophy in combination with white matter (WM integrity to distinguish behavioral variant frontotemporal dementia (bvFTD from Alzheimer's disease (AD and from controls using voxel-based morphometry, subcortical structure segmentation, and tract-based spatial statistics. To determine which combination of MR markers differentiated the three groups with the highest accuracy, we conducted discriminant function analyses. Adjusted for age, sex and center, both types of dementia had more GM atrophy, lower fractional anisotropy (FA and higher mean (MD, axial (L1 and radial diffusivity (L23 values than controls. BvFTD patients had more GM atrophy in orbitofrontal and inferior frontal areas than AD patients. In addition, caudate nucleus and nucleus accumbens were smaller in bvFTD than in AD. FA values were lower; MD, L1 and L23 values were higher, especially in frontal areas of the brain for bvFTD compared to AD patients. The combination of cortical GM, hippocampal volume and WM integrity measurements, classified 97–100% of controls, 81–100% of AD and 67–75% of bvFTD patients correctly. Our results suggest that WM integrity measures add complementary information to measures of GM atrophy, thereby improving the classification between AD and bvFTD.

  13. Lateral Pectoral Nerve Injury Mimicking Cervical Radiculopathy.

    Science.gov (United States)

    Aktas, Ilknur; Palamar, Deniz; Akgun, Kenan

    2015-07-01

    The lateral pectoral nerve (LPN) is commonly injured along with the brachial plexus, but its isolated lesions are rare. Here, we present a case of an isolated LPN lesion confused with cervical radiculopathy. A 41-year-old man was admitted to our clinic because of weakness in his right arm. Previous magnetic resonance imaging (MRI) examination revealed right posterolateral protrusion at the C6-7 level. At the initial assessment, atrophy of the right pectoralis major muscle was evident, and mild weakness of the right shoulder adductor, internal rotator, and flexor muscles was observed. Therefore, electrodiagnostic evaluation was performed, and a diagnosis of isolated LPN injury was made. Nerve injury was thought to have been caused by weightlifting exercises and traction injury. Lateral pectoral nerve injury can mimic cervical radiculopathy, and MRI examination alone may lead to misdiagnosis. Repeated physical examinations during the evaluation and treatment phase will identify the muscle atrophy that occurs 1 or more months after the injury.

  14. Cerebral perfusion changes in traumatic diffuse brain injury. IMP SPECT studies

    International Nuclear Information System (INIS)

    Ito, Hiroshi; Kawashima, Ryuta; Fukuda, Hiroshi; Ishii, Kiyoshi; Onuma, Takehide.

    1997-01-01

    Diffuse brain injury (DBI) is characterized by axonal degeneration and neuronal damage which cause diffuse brain atrophy. We have investigated the time course of abnormalities in cerebral perfusion distribution in cases of DBI by using Iodine-123-IMP SPECT, and the relationship to the appearance of diffuse brain atrophy. SPECT scans were performed on eight patients with diffuse brain injury due to closed cranial trauma in acute and chronic stages. All patients showed abnormalities in cerebral perfusion with decreases in perfusion, even in non-depicted regions on MRI, and the affected areas varied throughout the period of observation. Diffuse brain atrophy appeared in all patients. In some patients, diffuse brain atrophy was observed at or just after the time when the maximum number of lesions on SPECT were seen. The abnormalities in cerebral perfusion in cases of DBI might therefore be related to axonal degeneration and neuronal damage which causes diffuse brain atrophy. (author)

  15. Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline.

    Science.gov (United States)

    Risacher, Shannon L; Anderson, Wesley H; Charil, Arnaud; Castelluccio, Peter F; Shcherbinin, Sergey; Saykin, Andrew J; Schwarz, Adam J

    2017-11-21

    To test the hypothesis that cortical and hippocampal volumes, measured in vivo from volumetric MRI (vMRI) scans, could be used to identify variant subtypes of Alzheimer disease (AD) and to prospectively predict the rate of clinical decline. Amyloid-positive participants with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) 1 and ADNI2 with baseline MRI scans (n = 229) and 2-year clinical follow-up (n = 100) were included. AD subtypes (hippocampal sparing [HpSp MRI ], limbic predominant [LP MRI ], typical AD [tAD MRI ]) were defined according to an algorithm analogous to one recently proposed for tau neuropathology. Relationships between baseline hippocampal volume to cortical volume ratio (HV:CTV) and clinical variables were examined by both continuous regression and categorical models. When participants were divided categorically, the HpSp MRI group showed significantly more AD-like hypometabolism on 18 F-fluorodeoxyglucose-PET ( p Alzheimer's Disease Assessment Scale, 13-Item Subscale (ADAS-Cog 13 ), Mini-Mental State Examination (MMSE), and Functional Assessment Questionnaire (all p < 0.05) and tAD MRI on the MMSE and Clinical Dementia Rating Sum of Boxes (CDR-SB) (both p < 0.05). Finally, a larger HV:CTV was associated with poorer baseline executive function and a faster slope of decline in CDR-SB, MMSE, and ADAS-Cog 13 score ( p < 0.05). These associations were driven mostly by the amount of cortical rather than hippocampal atrophy. AD subtypes with phenotypes consistent with those observed with tau neuropathology can be identified in vivo with vMRI. An increased HV:CTV ratio was predictive of faster clinical decline in participants with AD who were clinically indistinguishable at baseline except for a greater dysexecutive presentation. © 2017 American Academy of Neurology.

  16. Brain atrophy during aging

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju; Takeda, Shumpei; Hatazawa, Jun

    1985-01-01

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT and following results were obtained. Brain atrophy was minimal in 34 -- 35 years old in both sexes, increased exponentially to the increasing age after 34 -- 35 years, and probably resulted in dementia, such as vascular or multiinfarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34 -- 35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extents of brain atrophy (20 -- 30 %) existed among aged subjects. Some aged subjects had little or no atrophy of their brains, as seen in young subjects, and others had markedly shrunken brains associated with senility. From these results there must be pathological factors promoting brain atrophy with a great individual difference. We have studied the relation of intelligence to brain volume, and have ascertained that progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was decrease in the cerebral blood flow. MNR-CT can easily detected small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy, while X-CT can not. Therefore NMR-CT is very useful for detection of subtle changes in the brain. (J.P.N.)

  17. Computed tomographic myelography characteristics of spinal cord atrophy in juvenile muscular atrophy of the upper extremity

    International Nuclear Information System (INIS)

    Hirabuki, Norio; Mitomo, Masanori; Miura, Takashi; Hashimoto, Tsutomu; Kawai, Ryuji; Kozuka, Takahiro

    1991-01-01

    Although atrophy of the lower cervical and upper thoracic cord in juvenile muscular atrophy of distal upper extremity has been reported, the atrophic patterns of the cord, especially in the transverse section, have not been studied extensively. The aim of this study is to clarify the atrophic patterns of the cord by CT myelography (CTM) and to discuss the pathogenesis of cord atrophy. Sixteen patients with juvenile muscular atrophy of distal upper extremity were examined by CTM. Atrophy of the lower cervical and upper thoracic cord, consistent with the segmental weakness, was seen in all patients. Flattening of the ventral convexity was a characteristic atrophic pattern of the cord. Bilateral cord atrophy was commonly observed; 8/12 patients with unilateral clinical form and all 4 patients with bilateral form showed bilateral cord atrophy with dominance on the clinical side. There was no correlation between the degree of cord atrophy and duration of symptoms. Flattening of the ventral convexity, associated with purely motor disturbances, reflects selective atrophy of the anterior horns in the cord, which is attributable to chronic ischemia. Cord atrophy proved to precede clinical manifestations. The characteristic atrophy of the cord provides useful information to confirm the diagnosis without long-term observation. (author). 21 refs.; 3 figs.; 2 tabs

  18. Lipomatous muscle atrophy caused by irradiation exposure

    International Nuclear Information System (INIS)

    Rhomberg, W.; Hergan, K.

    1990-01-01

    As compared to other organs and tissues liable to sustain delayed injury from radiotherapy, the musculature seems to be a hard-wearing, radiation-resistant organ. Apart from the possibility of inducing Myodegeneratio cordis, muscles are merely threatened, as far as is known today, by possible fibrosis in the surrounding area. Certainly, extremely high doses of more than 100 Gy occasionally may trigger necrosis and atrophies in tissues. The article reports on a patient suffering from carcinoma of the bladder who developed muscle and tendon degeneration following telecobalt irradiation after a latency period of eight years, forcing him ultimately to quit work. (orig.) [de

  19. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment.

    Science.gov (United States)

    Papma, Janne M; Smits, Marion; de Groot, Marius; Mattace Raso, Francesco U; van der Lugt, Aad; Vrooman, Henri A; Niessen, Wiro J; Koudstaal, Peter J; van Swieten, John C; van der Veen, Frederik M; Prins, Niels D

    2017-09-01

    Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI.

  20. Morphologic and neuropsychological patterns in patients suffering from Alzheimer's disease

    International Nuclear Information System (INIS)

    Chapuis, Pierre; Banciu, Eldda; Sauvee, Mathilde; Serra, Amelie; Moreaud, Olivier; Medici, Maud; Moreau-Gaudry, Alexandre; Krainik, Alexandre

    2016-01-01

    We conducted a retrospective study to identify morphological subgroups of patients referred for AD or aMCI and to seek for differences across neuropsychological performances. One hundred forty-five patients (mean age = 76.01, 88 women and 57 men) referred for AD, either at the stage of dementia or aMCI, were examined using structural MRI. Five observers reviewed blindly twice all examinations. We rated microangiopathy, hippocampal, parietal atrophies, including a gradient of fronto-parietal atrophy (GFPA). A multiple component analysis (MCA) followed by a hierarchical ascending classification was conducted to identify morphologically distinct subgroups. Among these, 76 patients completed all the neuropsychological tests. Univariate and multivariate analyses were further conducted on these data across morphological subgroups. The institutional review board approved the research protocol. Inter- and intra-raters' agreements were excellent and very good for microangiopathy and hippocampal atrophy ratings. They were higher for GFPA than for the parietal atrophy scale. MCA without priors identified three groups: group 1 was characterized by no/discrete microangiopathy, severe hippocampal, and predominant parietal atrophy; group 2 had significant microangiopathy, severe hippocampal atrophy, and no predominant parietal atrophy; group 3 had a mild hippocampal atrophy and parietal atrophies. In group 1, working memory profile was less impaired than in group 2 (p = 0.01). Neuropsychological performances of group 3 were higher in most domains. Combined characterization of microangiopathy, hippocampal, parietal, and GFPA allows identifying morphological subgroups among patients referred for AD and at risk. These groups have some neuropsychological differences, suggesting different pathophysiological mechanisms or co-existing conditions. (orig.)

  1. Morphologic and neuropsychological patterns in patients suffering from Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Chapuis, Pierre; Banciu, Eldda [University Hospital of Grenoble, Department of Neuroradiology and MRI, Grenoble (France); Sauvee, Mathilde; Serra, Amelie; Moreaud, Olivier [University Hospital of Grenoble, Department of Neurology, Grenoble (France); Medici, Maud [CIT803, University Hospital of Grenoble, Grenoble (France); Moreau-Gaudry, Alexandre [CIT803, University Hospital of Grenoble, Grenoble (France); Joseph Fourier University, Grenoble (France); Krainik, Alexandre [University Hospital of Grenoble, Department of Neuroradiology and MRI, Grenoble (France); INSERM U 836, Grenoble Institute of Neurosciences, Grenoble (France)

    2016-05-15

    We conducted a retrospective study to identify morphological subgroups of patients referred for AD or aMCI and to seek for differences across neuropsychological performances. One hundred forty-five patients (mean age = 76.01, 88 women and 57 men) referred for AD, either at the stage of dementia or aMCI, were examined using structural MRI. Five observers reviewed blindly twice all examinations. We rated microangiopathy, hippocampal, parietal atrophies, including a gradient of fronto-parietal atrophy (GFPA). A multiple component analysis (MCA) followed by a hierarchical ascending classification was conducted to identify morphologically distinct subgroups. Among these, 76 patients completed all the neuropsychological tests. Univariate and multivariate analyses were further conducted on these data across morphological subgroups. The institutional review board approved the research protocol. Inter- and intra-raters' agreements were excellent and very good for microangiopathy and hippocampal atrophy ratings. They were higher for GFPA than for the parietal atrophy scale. MCA without priors identified three groups: group 1 was characterized by no/discrete microangiopathy, severe hippocampal, and predominant parietal atrophy; group 2 had significant microangiopathy, severe hippocampal atrophy, and no predominant parietal atrophy; group 3 had a mild hippocampal atrophy and parietal atrophies. In group 1, working memory profile was less impaired than in group 2 (p = 0.01). Neuropsychological performances of group 3 were higher in most domains. Combined characterization of microangiopathy, hippocampal, parietal, and GFPA allows identifying morphological subgroups among patients referred for AD and at risk. These groups have some neuropsychological differences, suggesting different pathophysiological mechanisms or co-existing conditions. (orig.)

  2. Childhood optic atrophy.

    Science.gov (United States)

    Mudgil, A V; Repka, M X

    2000-02-01

    To determine the causes, and relative incidence of the common causes, of optic nerve atrophy in children under 10 years old and to compare prevalent aetiologies with those given in previous studies. The Wilmer Information System database was searched to identify all children, diagnosed between 1987 and 1997 with optic atrophy, who were under 10 years old at diagnosis. The medical records of these children were reviewed retrospectively A total of 272 children were identified, Complications from premature birth were the most frequent aetiology of optic atrophy (n = 44, 16%); 68% of these premature infants having a history of intraventricular haemorrhage. Tumour was the second most common aetiology (n = 40, 15%). The most frequent tumour was pilocytic astrocytoma (50%), followed by craniopharyngioma (17%). Hydrocephalus, unrelated to tumour, was the third most common aetiology (n = 26, 10%). In 114 cases (42%), the cause of optic atrophy became manifest in the perinatal period and/or could be attributed to adverse events in utero. A cause was not determined in 4% of cases. In the last decade, prematurity and hydrocephalus appear to have become important causes of optic atrophy in childhood. This trend is probably the result of improved survival of infants with extremely low birth weight.

  3. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

    International Nuclear Information System (INIS)

    Papma, Janne M.; Koudstaal, Peter J.; Swieten, John C. van; Smits, Marion; Lugt, Aad van der; Groot, Marius de; Vrooman, Henri A.; Mattace Raso, Francesco U.; Niessen, Wiro J.; Veen, Frederik M. van der; Prins, Niels D.

    2017-01-01

    Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. (orig.)

  4. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

    Energy Technology Data Exchange (ETDEWEB)

    Papma, Janne M.; Koudstaal, Peter J.; Swieten, John C. van [Erasmus MC - University Medical Center Rotterdam, Department of Neurology, Rotterdam (Netherlands); Smits, Marion; Lugt, Aad van der [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, Rotterdam (Netherlands); Groot, Marius de; Vrooman, Henri A. [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, Rotterdam (Netherlands); Erasmus MC - University Medical Center Rotterdam, Department of Medical Informatics, Rotterdam (Netherlands); Mattace Raso, Francesco U. [Erasmus MC - University Medical Center Rotterdam, Department of Geriatrics, Rotterdam (Netherlands); Niessen, Wiro J. [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, Rotterdam (Netherlands); Erasmus MC - University Medical Center Rotterdam, Department of Medical Informatics, Rotterdam (Netherlands); Delft University of Technology, Faculty of Applied Sciences, Delft (Netherlands); Veen, Frederik M. van der [Erasmus University Rotterdam, Institute of Psychology, Rotterdam (Netherlands); Prins, Niels D. [VU University Medical Center, Alzheimer Center, Department of Neurology, Amsterdam (Netherlands)

    2017-09-15

    Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. (orig.)

  5. Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood.

    Science.gov (United States)

    Wong-Goodrich, Sarah J E; Tognoni, Christina M; Mellott, Tiffany J; Glenn, Melissa J; Blusztajn, Jan K; Williams, Christina L

    2011-09-21

    Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12-17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Validation of hippocampal volumes measured using a manual method and two automated methods (FreeSurfer and IBASPM) in chronic major depressive disorder

    Energy Technology Data Exchange (ETDEWEB)

    Tae, Woo Suk; Lee, Kang Uk; Nam, Eui-Cheol; Kim, Keun Woo [Kangwon National University College of Medicine, Neuroscience Research Institute, Kangwon (Korea); Kim, Sam Soo [Kangwon National University College of Medicine, Neuroscience Research Institute, Kangwon (Korea); Kangwon National University Hospital, Department of Radiology, Kangwon-do (Korea)

    2008-07-15

    To validate the usefulness of the packages available for automated hippocampal volumetry, we measured hippocampal volumes using one manual and two recently developed automated volumetric methods. The study included T1-weighted magnetic resonance imaging (MRI) of 21 patients with chronic major depressive disorder (MDD) and 20 normal controls. Using coronal turbo field echo (TFE) MRI with a slice thickness of 1.3 mm, the hippocampal volumes were measured using three methods: manual volumetry, surface-based parcellation using FreeSurfer, and individual atlas-based volumetry using IBASPM. In addition, the intracranial cavity volume (ICV) was measured manually. The absolute left hippocampal volume of the patients with MDD measured using all three methods was significantly smaller than the left hippocampal volume of the normal controls (manual P=0.029, FreeSurfer P=0.035, IBASPM P=0.018). After controlling for the ICV, except for the right hippocampal volume measured using FreeSurfer, both measured hippocampal volumes of the patients with MDD were significantly smaller than the measured hippocampal volumes of the normal controls (right manual P=0.019, IBASPM P=0.012; left manual P=0.003, FreeSurfer P=0.010, IBASPM P=0.002). In the intrarater reliability test, the intraclass correlation coefficients (ICCs) were all excellent (manual right 0.947, left 0.934; FreeSurfer right 1.000, left 1.000; IBASPM right 1.000, left 1.000). In the test of agreement between the volumetric methods, the ICCs were right 0.846 and left 0.848 (manual and FreeSurfer), and right 0.654 and left 0.717 (manual and IBASPM). The automated hippocampal volumetric methods showed good agreement with manual hippocampal volumetry, but the volume measured using FreeSurfer was 35% larger and the agreement was questionable with IBASPM. Although the automated methods could detect hippocampal atrophy in the patients with MDD, the results indicate that manual hippocampal volumetry is still the gold standard

  7. Validation of hippocampal volumes measured using a manual method and two automated methods (FreeSurfer and IBASPM) in chronic major depressive disorder

    International Nuclear Information System (INIS)

    Tae, Woo Suk; Lee, Kang Uk; Nam, Eui-Cheol; Kim, Keun Woo; Kim, Sam Soo

    2008-01-01

    To validate the usefulness of the packages available for automated hippocampal volumetry, we measured hippocampal volumes using one manual and two recently developed automated volumetric methods. The study included T1-weighted magnetic resonance imaging (MRI) of 21 patients with chronic major depressive disorder (MDD) and 20 normal controls. Using coronal turbo field echo (TFE) MRI with a slice thickness of 1.3 mm, the hippocampal volumes were measured using three methods: manual volumetry, surface-based parcellation using FreeSurfer, and individual atlas-based volumetry using IBASPM. In addition, the intracranial cavity volume (ICV) was measured manually. The absolute left hippocampal volume of the patients with MDD measured using all three methods was significantly smaller than the left hippocampal volume of the normal controls (manual P=0.029, FreeSurfer P=0.035, IBASPM P=0.018). After controlling for the ICV, except for the right hippocampal volume measured using FreeSurfer, both measured hippocampal volumes of the patients with MDD were significantly smaller than the measured hippocampal volumes of the normal controls (right manual P=0.019, IBASPM P=0.012; left manual P=0.003, FreeSurfer P=0.010, IBASPM P=0.002). In the intrarater reliability test, the intraclass correlation coefficients (ICCs) were all excellent (manual right 0.947, left 0.934; FreeSurfer right 1.000, left 1.000; IBASPM right 1.000, left 1.000). In the test of agreement between the volumetric methods, the ICCs were right 0.846 and left 0.848 (manual and FreeSurfer), and right 0.654 and left 0.717 (manual and IBASPM). The automated hippocampal volumetric methods showed good agreement with manual hippocampal volumetry, but the volume measured using FreeSurfer was 35% larger and the agreement was questionable with IBASPM. Although the automated methods could detect hippocampal atrophy in the patients with MDD, the results indicate that manual hippocampal volumetry is still the gold standard

  8. Boosted Regeneration and Reduced Denervated Muscle Atrophy by NeuroHeal in a Pre-clinical Model of Lumbar Root Avulsion with Delayed Reimplantation.

    Science.gov (United States)

    Romeo-Guitart, David; Forés, Joaquim; Navarro, Xavier; Casas, Caty

    2017-09-20

    The "gold standard" treatment of patients with spinal root injuries consists of delayed surgical reconnection of nerves. The sooner, the better, but problems such as injury-induced motor neuronal death and muscle atrophy due to long-term denervation mean that normal movement is not restored. Herein we describe a preclinical model of root avulsion with delayed reimplantation of lumbar roots that was used to establish a new adjuvant pharmacological treatment. Chronic treatment (up to 6 months) with NeuroHeal, a new combination drug therapy identified using a systems biology approach, exerted long-lasting neuroprotection, reduced gliosis and matrix proteoglycan content, accelerated nerve regeneration by activating the AKT pathway, promoted the formation of functional neuromuscular junctions, and reduced denervation-induced muscular atrophy. Thus, NeuroHeal is a promising treatment for spinal nerve root injuries and axonal regeneration after trauma.

  9. Computed tomography in alcoholic cerebellar atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Haubek, A; Lee, K [Hvidovre Hospital Copenhagen (Denmark). Dept. of Radiology; Municipal Hospital, Copenhagen (Denmark). Dept. of Neurology)

    1979-01-01

    This is a controlled CT evaluation of the infratentorial region in 41 male alcoholics under age 35. Criteria for the presence of atrophy are outlined. Twelve patients had cerebellar atrophy. Vermian atrophy was present in all. Atrophy of the cerebellar hemispheres was demonstrated in eight patients as well. The results are statistically significant when compared to an age-matched group of 40 non-alcoholic males among whom two cases of vermian atrophy were found. There were clinical signs of alcoholic cerebellar atrophy in one patient only. The disparity between the clinical and the radiological data are discussed with reference to previous pneumoencephalographic findings. (orig.) 891 AJ/orig. 892 MKO.

  10. Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT: Classification of Atrophy Report 3.

    Science.gov (United States)

    Sadda, Srinivas R; Guymer, Robyn; Holz, Frank G; Schmitz-Valckenberg, Steffen; Curcio, Christine A; Bird, Alan C; Blodi, Barbara A; Bottoni, Ferdinando; Chakravarthy, Usha; Chew, Emily Y; Csaky, Karl; Danis, Ronald P; Fleckenstein, Monika; Freund, K Bailey; Grunwald, Juan; Hoyng, Carel B; Jaffe, Glenn J; Liakopoulos, Sandra; Monés, Jordi M; Pauleikhoff, Daniel; Rosenfeld, Philip J; Sarraf, David; Spaide, Richard F; Tadayoni, Ramin; Tufail, Adnan; Wolf, Sebastian; Staurenghi, Giovanni

    2018-04-01

    To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD). Consensus meeting. Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers. As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy. A consensus classification system for atrophy and OCT-based criteria to identify atrophy. OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear. A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete

  11. Muscular atrophy in diabetic neuropathy

    DEFF Research Database (Denmark)

    Andersen, H; Gadeberg, P C; Brock, B

    1997-01-01

    Diabetic patients with polyneuropathy develop motor dysfunction. To establish whether motor dysfunction is associated with muscular atrophy the ankle dorsal and plantar flexors of the non-dominant leg were evaluated with magnetic resonance imaging in 8 patients with symptomatic neuropathy, in 8 non...... confirmed that the atrophy predominated distally. We conclude that muscular atrophy underlies motor weakness at the ankle in diabetic patients with polyneuropathy and that the atrophy is most pronounced in distal muscles of the lower leg indicating that a length dependent neuropathic process explains...

  12. Clinical Study White Matter Atrophy in Patients with Mesial Temporal Lobe Epilepsy: Voxel-Based Morphometry Analysis of T1- and T2-Weighted MR Images

    International Nuclear Information System (INIS)

    Braga, B.; Yasuda, C.L.; Cendes, F.

    2012-01-01

    Introduction. Mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis is highly refractory to clinical treatment. MRI voxel-based morphometry (VBM) of T1-weighted images has revealed a widespread pattern of gray matter (GM) and white matter (WM) atrophy in MTLE. Few studies have investigated the role of T2-weighted images in revealing WM atrophy using VBM. Objectives. To compare the results of WM atrophy between T1- and T2-weighted images through VBM. Methods. We selected 28 patients with left and 27 with right MTLE and 60 normal controls. We analyzed T1- and T2- weighted images with SPM8, using VBM/DARTEL algorithm to extract maps of GM and WM. The second level of SPM was used to investigate areas of WM atrophy among groups. Results. Both acquisitions showed bilateral widespread WM atrophy. T1-weighted images showed higher sensibility to detect areas of WM atrophy in both groups of MTLE. T2-weighted images also showed areas of WM atrophy in a more restricted pattern, but still bilateral and with a large area of superposition with T1-weighted images. Conclusions. In MTLE, T1-weighted images are more sensitive to detect subtle WM abnormalities using VBM, compared to T2 images, although both present a good superposition of statistical maps. 1. Introduction The mesial temporal lobe epilepsy (MTLE) is highly refractory to pharmacological treatment [1], and it is the main group of epilepsy referred to the tertiary care hospitals for surgical treatment [2]. MTLE shows a good surgical prognosis, with satisfactory seizures control in 60-80% of the patients [3]. In approximately 65%

  13. Hippocampal Dysfunction Provoked by Mercury Chloride Exposure: Evaluation of Cognitive Impairment, Oxidative Stress, Tissue Injury and Nature of Cell Death

    Directory of Open Access Journals (Sweden)

    Walessa Alana Bragança Aragão

    2018-01-01

    Full Text Available Mercury (Hg is a highly toxic metal, which can be found in its inorganic form in the environment. This form presents lower liposolubility and lower absorption in the body. In order to elucidate the possible toxicity of inorganic Hg in the hippocampus, we investigated the potential of low doses of mercury chloride (HgCl2 to promote hippocampal dysfunction by employing a chronic exposure model. For this, 56 rats were exposed to HgCl2 (0.375 mg/kg/day via the oral route for 45 days. After the exposure period, the animals were submitted to the cognitive test of fear memory. The hippocampus was collected for the measurement of total Hg levels, analysis of oxidative stress, and evaluation of cytotoxicity, apoptosis, and tissue injury. It was observed that chronic exposure to inorganic Hg promotes an increase in mercury levels in this region and damage to short- and long-term memory. Furthermore, we found that this exposure model provoked oxidative stress, which led to cytotoxicity and cell death by apoptosis, affecting astrocytes and neurons in the hippocampus. Our study demonstrated that inorganic Hg, even with its low liposolubility, is able to produce deleterious effects in the central nervous system, resulting in cognitive impairment and hippocampal damage when administered for a long time at low doses in rats.

  14. Comparison between MRI and 3D-SSP in olivopontocerebellar atrophy and cortical cerebellar atrophy

    International Nuclear Information System (INIS)

    Hamaguchi, Hirotoshi; Kanda, Fumio; Hosaka, Kayo; Fujii, Masahiko; Chihara, Kazuo

    2004-01-01

    We compared images of three-dimensional stereotactic surface projections (3D-SSP) of SPECT with MRI images in spinocerebellar degeneration patients (13 olivopontocerebellar atrophy (OPCA) and 7 cortical cerebellar atrophy (CCA)). We analyzed a brain blood flow pattern with an image of statistics by 123 I-IMP SPECT. In OPCA patients, a blood flow reduction was more remarkable in 3D-SSP than a degree of cerebellar atrophy in MRI. In patients with CCA, the cerebellum showed little blood flow reduction in 3D-SSP despite of apparent atrophy in MRI. Simultaneous examination both MRI and 3D-SSP might be useful for differential diagnosis of spinocerebellar degenerations. (author)

  15. Methods to induce primary and secondary traumatic damage in organotypic hippocampal slice cultures.

    Science.gov (United States)

    Adamchik, Y; Frantseva, M V; Weisspapir, M; Carlen, P L; Perez Velazquez, J L

    2000-04-01

    Organotypic brain slice cultures have been used in a variety of studies on neurodegenerative processes [K.M. Abdel-Hamid, M. Tymianski, Mechanisms and effects of intracellular calcium buffering on neuronal survival in organotypic hippocampal cultures exposed to anoxia/aglycemia or to excitotoxins, J. Neurosci. 17, 1997, pp. 3538-3553; D.W. Newell, A. Barth, V. Papermaster, A.T. Malouf, Glutamate and non-glutamate receptor mediated toxicity caused by oxygen and glucose deprivation in organotypic hippocampal cultures, J. Neurosci. 15, 1995, pp. 7702-7711; J.L. Perez Velazquez, M.V. Frantseva, P.L. Carlen, In vitro ischemia promotes glutamate mediated free radical generation and intracellular calcium accumulation in pyramidal neurons of cultured hippocampal slices, J. Neurosci. 23, 1997, pp. 9085-9094; L. Stoppini, L.A. Buchs, D. Muller, A simple method for organotypic cultures of nervous tissue, J. Neurosci. Methods 37, 1991, pp. 173-182; R.C. Tasker, J.T. Coyle, J.J. Vornov, The regional vulnerability to hypoglycemia induced neurotoxicity in organotypic hippocampal culture: protection by early tetrodotoxin or delayed MK 801, J. Neurosci. 12, 1992, pp. 4298-4308.]. We describe two methods to induce traumatic cell damage in hippocampal organotypic cultures. Primary trauma injury was achieved by rolling a stainless steel cylinder (0.9 g) on the organotypic slices. Secondary injury was followed after dropping a weight (0.137 g) on a localised area of the organotypic slice, from a height of 2 mm. The time course and extent of cell death were determined by measuring the fluorescence of the viability indicator propidium iodide (PI) at several time points after the injury. The initial localised impact damage spread 24 and 67 h after injury, cell death being 25% and 54%, respectively, when slices were kept at 37 degrees C. To validate these methods as models to assess neuroprotective strategies, similar insults were applied to slices at relatively low temperatures (30

  16. Classification of Alzheimer's disease patients with hippocampal shape wrapper-based feature selection and support vector machine

    Science.gov (United States)

    Young, Jonathan; Ridgway, Gerard; Leung, Kelvin; Ourselin, Sebastien

    2012-02-01

    It is well known that hippocampal atrophy is a marker of the onset of Alzheimer's disease (AD) and as a result hippocampal volumetry has been used in a number of studies to provide early diagnosis of AD and predict conversion of mild cognitive impairment patients to AD. However, rates of atrophy are not uniform across the hippocampus making shape analysis a potentially more accurate biomarker. This study studies the hippocampi from 226 healthy controls, 148 AD patients and 330 MCI patients obtained from T1 weighted structural MRI images from the ADNI database. The hippocampi are anatomically segmented using the MAPS multi-atlas segmentation method, and the resulting binary images are then processed with SPHARM software to decompose their shapes as a weighted sum of spherical harmonic basis functions. The resulting parameterizations are then used as feature vectors in Support Vector Machine (SVM) classification. A wrapper based feature selection method was used as this considers the utility of features in discriminating classes in combination, fully exploiting the multivariate nature of the data and optimizing the selected set of features for the type of classifier that is used. The leave-one-out cross validated accuracy obtained on training data is 88.6% for classifying AD vs controls and 74% for classifying MCI-converters vs MCI-stable with very compact feature sets, showing that this is a highly promising method. There is currently a considerable fall in accuracy on unseen data indicating that the feature selection is sensitive to the data used, however feature ensemble methods may overcome this.

  17. Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Nabi Shamsaei; Mehdi Khaksari; Sohaila Erfani; Hamid Rajabi; Nahid Aboutaleb

    2015-01-01

    Recent evidence has suggested the neuroprotective effects of physical exercise on cerebral isch-emic injury. However, the role of physical exercise in cerebral ischemia-induced hippocampal damage remains controversial. The aim of the present study was to evaluate the effects of pre-ischemia treadmill training on hippocampal CA1 neuronal damage after cerebral ischemia. Male adult rats were randomly divided into control, ischemia and exercise + ischemia groups. In the exercise + ischemia group, rats were subjected to running on a treadmill in a designated time schedule (5 days per week for 4 weeks). Then rats underwent cerebral ischemia induction th rough occlusion of common carotids followed by reperfusion. At 4 days after cerebral ischemia, rat learning and memory abilities were evaluated using passive avoidance memory test and rat hippocampal neuronal damage was detected using Nissl and TUNEL staining. Pre-ischemic ex-ercise signiifcantly reduced the number of TUNEL-positive cells and necrotic cell death in the hippocampal CA1 region as compared to the ischemia group. Moreover, pre-ischemic exercise significantly prevented ischemia-induced memory dysfunction. Pre-ischemic exercise mighct prevent memory deficits after cerebral ischemia through rescuing hippocampal CA1 neurons from ischemia-induced degeneration.

  18. Both oophorectomy and obesity impaired solely hippocampal-dependent memory via increased hippocampal dysfunction.

    Science.gov (United States)

    Mantor, Duangkamol; Pratchayasakul, Wasana; Minta, Wanitchaya; Sutham, Wissuta; Palee, Siripong; Sripetchwandee, Jirapas; Kerdphoo, Sasiwan; Jaiwongkum, Thidarat; Sriwichaiin, Sirawit; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2018-04-17

    Our previous study demonstrated that obesity aggravated peripheral insulin resistance and brain dysfunction in the ovariectomized condition. Conversely, the effect of obesity followed by oophorectomy on brain oxidative stress, brain apoptosis, synaptic function and cognitive function, particularly in hippocampal-dependent and hippocampal-independent memory, has not been investigated. Our hypothesis was that oophorectomy aggravated metabolic impairment, brain dysfunction and cognitive impairment in obese rats. Thirty-two female rats were fed with either a normal diet (ND, n = 16) or a high-fat diet (HFD, n = 16) for a total of 20 weeks. At week 13, rats in each group were subdivided into sham and ovariectomized subgroups (n = 8/subgroup). At week 20, all rats were tested for hippocampal-dependent and hippocampal-independent memory by using Morris water maze test (MWM) and Novel objective recognition (NOR) tests, respectively. We found that the obese-insulin resistant condition occurred in sham-HFD-fed rats (HFS), ovariectomized-ND-fed rats (NDO), and ovariectomized-HFD-fed rats (HFO). Increased hippocampal oxidative stress level, increased hippocampal apoptosis, increased hippocampal synaptic dysfunction, decreased hippocampal estrogen level and impaired hippocampal-dependent memory were observed in HFS, NDO, and HFO rats. However, the hippocampal-independent memory, cortical estrogen levels, cortical ROS production, and cortical apoptosis showed no significant difference between groups. These findings suggested that oophorectomy and obesity exclusively impaired hippocampal-dependent memory, possibly via increased hippocampal dysfunction. Nonetheless, oophorectomy did not aggravate these deleterious effects under conditions of obesity. Copyright © 2017. Published by Elsevier Inc.

  19. Susceptibility to hippocampal kindling seizures is increased in aging C57 black mice

    Directory of Open Access Journals (Sweden)

    Kurt R. Stover

    2017-12-01

    Full Text Available The incidence of seizures increases with old age. Stroke, dementia and brain tumors are recognized risk factors for new-onset seizures in the aging populations and the incidence of these conditions also increased with age. Whether aging is associated with higher seizure susceptibility in the absence of the above pathologies remains unclear. We used classic kindling to explore this issue as the kindling model is highly reproducible and allows close monitoring of electrographic and motor seizure activities in individual animals. We kindled male young and aging mice (C57BL/6 strain, 2–3 and 18–22 months of age via daily hippocampal CA3 stimulation and monitored seizure activity via video and electroencephalographic recordings. The aging mice needed fewer stimuli to evoke stage-5 motor seizures and exhibited longer hippocampal afterdischarges and more frequent hippocampal spikes relative to the young mice, but afterdischarge thresholds and cumulative afterdischarge durations to stage 5 motor seizures were not different between the two age groups. While hippocampal injury and structural alterations at cellular and micro-circuitry levels remain to be examined in the kindled mice, our present observations suggest that susceptibility to hippocampal CA3 kindling seizures is increased with aging in male C57 black mice.

  20. A locus identified on chromosome18p11.31 is associated with hippocampal abnormalities in a family with mesial temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Claudia Vianna Maurer-Morelli

    2012-08-01

    Full Text Available We aimed to identify the region harboring a putative candidate gene associated with hippocampal abnormalities (HAb in a family with mesial temporal lobe epilepsy (MTLE. Genome-wide scan was performed in one large kindred with MTLE using a total of 332 microsatellite markers at ~12cM intervals. An additional 13 markers were genotyped in the candidate region. Phenotypic classes were defined according to the presence of hippocampal atrophy and/or hyperintense hippocampal T2 signal detected on magnetic resonance imaging. We identified a significant positive LOD score on chromosome 18p11.31 with a Zmax of 3.12 at D18S452. Multipoint LOD scores and haplotype analyses localized the candidate locus within a 6cM interval flanked by D18S976 and D18S967. We present here evidence that HAb, which were previously related mainly to environmental risk factors, may be influenced by genetic predisposition. This finding may have major impact in the study of the mechanisms underlying abnormalities in mesial temporal lobe structures and their relationship with MTLE.

  1. Cerebellar atrophy in epileptic patients

    International Nuclear Information System (INIS)

    Taneva, N.

    1991-01-01

    52 patients with epileptic seizures of different form, frequency and duration who had received long term treatment with anticonvulsive drugs were examined on Siretom 2000, a brain scanner of II generation. 6 standard incisions were made in all patients in the area of cerebellum, side ventricules and high convexity. Additional scanning with an incision width of 5 mm was made when pathological changes were detected. There were found 3 cases of cerebellar atrophy, 3 - cerebral atrophy, 1 - combined atrophy and 4 - with other changes. It was difficult to establish any relation between the rerebellar atrophy and the type of anticonvulsant used because treatment had usually been complex. 1 fig., 1 tab., 4 refs

  2. Insular and Hippocampal Gray Matter Volume Reductions in Patients with Major Depressive Disorder

    Science.gov (United States)

    Kugel, Harald; Krug, Axel; Schöning, Sonja; Ohrmann, Patricia; Uhlmann, Christina; Postert, Christian; Suslow, Thomas; Heindel, Walter; Arolt, Volker; Kircher, Tilo; Dannlowski, Udo

    2014-01-01

    Background Major depressive disorder is a serious psychiatric illness with a highly variable and heterogeneous clinical course. Due to the lack of consistent data from previous studies, the study of morphometric changes in major depressive disorder is still a major point of research requiring additional studies. The aim of the study presented here was to characterize and quantify regional gray matter abnormalities in a large sample of clinically well-characterized patients with major depressive disorder. Methods For this study one-hundred thirty two patients with major depressive disorder and 132 age- and gender-matched healthy control participants were included, 35 with their first episode and 97 with recurrent depression. To analyse gray matter abnormalities, voxel-based morphometry (VBM8) was employed on T1 weighted MRI data. We performed whole-brain analyses as well as a region-of-interest approach on the hippocampal formation, anterior cingulate cortex and amygdala, correlating the number of depressive episodes. Results Compared to healthy control persons, patients showed a strong gray-matter reduction in the right anterior insula. In addition, region-of-interest analyses revealed significant gray-matter reductions in the hippocampal formation. The observed alterations were more severe in patients with recurrent depressive episodes than in patients with a first episode. The number of depressive episodes was negatively correlated with gray-matter volume in the right hippocampus and right amygdala. Conclusions The anterior insula gray matter structure appears to be strongly affected in major depressive disorder and might play an important role in the neurobiology of depression. The hippocampal and amygdala volume loss cumulating with the number of episodes might be explained either by repeated neurotoxic stress or alternatively by higher relapse rates in patients showing hippocampal atrophy. PMID:25051163

  3. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis

    Directory of Open Access Journals (Sweden)

    De-An Zhao

    Full Text Available Abstract Background and objectives: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. Methods: A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Results: Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Conclusions: Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis.

  4. Efficacy of the fluid attenuated inversion recovery (FLAIR) sequence of MRI as a preoperative diagnosis of hippocampal sclerosis

    International Nuclear Information System (INIS)

    Morioka, Takato; Nishio, Shunji; Mihara, Futoshi; Muraishi, Mitsuteru; Hisada, Kei; Hasuo, Kanehiro; Fukui, Masashi

    1998-01-01

    A newly advanced MRI pulse sequence, the FLAIR (fluid attenuated inversion recovery) imaging, in which a long TE spin echo sequence is used with suppression of the CSF with an inversion pulse, displays the CSF space as a no-signal intensity area. There have been only a few reports on the FLAIR pulse sequence of temporal lobe epilepsy (TLE) as yet. We examined 9 cases of intractable TLE by FLAIR images and analyzed the advantages and disadvantages of the FLAIR pulse sequence for decision making on temporal lobectomy. All patients underwent anterior temporal lobectomy with hippocampectomy, and the diagnoses were confirmed histologically after surgery. Abnormally high T2 signals (HT2S) were more conspicuous with the FLAIR sequence than with any of the conventional sequences. Tilted axial plane, orientated along to the long axis of the hippocampal body, clearly demonstrated hippocampal atrophy (HA). Selection of a FLAIR sequence into the routine MR examination of patients with TLE is recommended. (author)

  5. Bilateral hippocampal hyperintensities: a new finding in MR imaging of heat stroke

    Energy Technology Data Exchange (ETDEWEB)

    Janaki Sudhakar, Praharaju; Al-Hashimi, Hakima [Salmaniya Medical Complex, Department of Radiology, Manama (Bahrain)

    2007-12-15

    We present a child aged 2 years 3 months who suffered heat stroke after being accidentally locked in a car during summer. She was unconscious with hyperthermia on admission and later showed biochemical evidence of liver, cardiac and muscle injury and associated electrolyte imbalance. Her level of consciousness gradually improved, but she showed evidence of cortical blindness, which had improved on follow-up. MR imaging on the 5th day revealed bilateral hippocampal hyperintensities along with hyperintensities in the cerebellum and in the cerebral cortex. Previous case reports of imaging in heat stroke revealed involvement of the cerebellum, thalami, basal ganglia and scattered cerebral involvement. We report this unique finding of hippocampal hyperintensities due to heat stroke. (orig.)

  6. Bilateral hippocampal hyperintensities: a new finding in MR imaging of heat stroke

    International Nuclear Information System (INIS)

    Janaki Sudhakar, Praharaju; Al-Hashimi, Hakima

    2007-01-01

    We present a child aged 2 years 3 months who suffered heat stroke after being accidentally locked in a car during summer. She was unconscious with hyperthermia on admission and later showed biochemical evidence of liver, cardiac and muscle injury and associated electrolyte imbalance. Her level of consciousness gradually improved, but she showed evidence of cortical blindness, which had improved on follow-up. MR imaging on the 5th day revealed bilateral hippocampal hyperintensities along with hyperintensities in the cerebellum and in the cerebral cortex. Previous case reports of imaging in heat stroke revealed involvement of the cerebellum, thalami, basal ganglia and scattered cerebral involvement. We report this unique finding of hippocampal hyperintensities due to heat stroke. (orig.)

  7. Thyroid Hormone Supplementation Restores Spatial Memory, Hippocampal Markers of Neuroinflammation, Plasticity-Related Signaling Molecules, and β-Amyloid Peptide Load in Hypothyroid Rats.

    Science.gov (United States)

    Chaalal, Amina; Poirier, Roseline; Blum, David; Laroche, Serge; Enderlin, Valérie

    2018-05-23

    Hypothyroidism is a condition that becomes more prevalent with age. Patients with untreated hypothyroidism have consistently reported symptoms of severe cognitive impairments. In patients suffering hypothyroidism, thyroid hormone supplementation offers the prospect to alleviate the cognitive consequences of hypothyroidism; however, the therapeutic value of TH supplementation remains at present uncertain and the link between cellular modifications associated with hypothyroidism and neurodegeneration remains to be elucidated. In the present study, we therefore evaluated the molecular and behavioral consequences of T3 hormone replacement in an animal model of hypothyroidism. We have previously reported that the antithyroid molecule propylthiouracil (PTU) given in the drinking water favors cerebral atrophy, brain neuroinflammation, Aβ production, Tau hyperphosphorylation, and altered plasticity-related cell-signaling pathways in the hippocampus in association with hippocampal-dependent spatial memory deficits. In the present study, our aim was to explore, in this model, the effect of hippocampal T3 signaling normalization on various molecular mechanisms involved in learning and memory that goes awry under conditions of hypothyroidism and to evaluate its potential for recovery of hippocampal-dependent memory deficits. We report that T3 supplementation can alleviate hippocampal-dependent memory impairments displayed by hypothyroid rats and normalize key markers of thyroid status in the hippocampus, of neuroinflammation, Aβ production, and of cell-signaling pathways known to be involved in synaptic plasticity and memory function. Together, these findings suggest that normalization of hippocampal T3 signaling is sufficient to reverse molecular and cognitive dysfunctions associated with hypothyroidism.

  8. Single-cell axotomy of cultured hippocampal neurons integrated in neuronal circuits.

    Science.gov (United States)

    Gomis-Rüth, Susana; Stiess, Michael; Wierenga, Corette J; Meyn, Liane; Bradke, Frank

    2014-05-01

    An understanding of the molecular mechanisms of axon regeneration after injury is key for the development of potential therapies. Single-cell axotomy of dissociated neurons enables the study of the intrinsic regenerative capacities of injured axons. This protocol describes how to perform single-cell axotomy on dissociated hippocampal neurons containing synapses. Furthermore, to axotomize hippocampal neurons integrated in neuronal circuits, we describe how to set up coculture with a few fluorescently labeled neurons. This approach allows axotomy of single cells in a complex neuronal network and the observation of morphological and molecular changes during axon regeneration. Thus, single-cell axotomy of mature neurons is a valuable tool for gaining insights into cell intrinsic axon regeneration and the plasticity of neuronal polarity of mature neurons. Dissociation of the hippocampus and plating of hippocampal neurons takes ∼2 h. Neurons are then left to grow for 2 weeks, during which time they integrate into neuronal circuits. Subsequent axotomy takes 10 min per neuron and further imaging takes 10 min per neuron.

  9. Evaluation of hepatic atrophy after transcatheter arterial embolization

    International Nuclear Information System (INIS)

    Chung, Hwan Hoon; Lee, Mee Ran; Oh, Min Cheol; Park, Chul Min; Seol, Hae Young; Cha, In Ho

    1995-01-01

    Hepatic atrophy has been recognized as a complication of hepatic and biliary disease but we have often found it in follow up CT after transcatheter arterial embolization (TACE). The purpose of this study is to evaluate the characteristics of hepatic atrophy after TACE. Of 53 patients who had TACE. We evaluated the relationship between the incidence of hepatic atrophy and the number of TACE, and also evaluated the average number of TACE in patients with hepatic atrophy. Of 20 patients who had received more than average number of TACE for development of hepatic atrophy (2 times with portal vein obstruction, 2.7 times without portal vein obstruction in this study), we evaluated the relationship between the lipiodol uptake pattern of tumor and the incidence of hepatic atrophy. There were 8 cases of hepatic atrophy (3 with portal vein obstruction, 5 without portal vein obstruction), average number for development of hepatic atrophy were 2.5 times. As the number of TACE were increased, the incidence of hepatic atrophy were also increased. Of 20 patients who received more than average number of TACE for development of hepatic atrophy, we noted 6 cases of hepatic atrophy in 11 patients with dense homogenous lipiodol uptake pattern of tumor and noted only 1 case of hepatic atrophy in 9 patient with inhomogenous lipiodol uptake pattern. Hepatic atrophy was one of the CT findings after TACE even without portal vein obstruction. Average number of TACE was 2.5 times and risk factors for development of hepatic atrophy were portal vein obstruction, increased number of TACE, and dense homogenous lipiodol uptake pattern of tumor

  10. Reduced age-related degeneration of the hippocampal subiculum in long-term meditators.

    Science.gov (United States)

    Kurth, Florian; Cherbuin, Nicolas; Luders, Eileen

    2015-06-30

    Normal aging is known to result in a reduction of gray matter within the hippocampal complex, particularly in the subiculum. The present study was designed to address the question whether the practice of meditation can amend this age-related subicular atrophy. For this purpose, we established the correlations between subicular volume and chronological age within 50 long-term meditators and 50 control subjects. High-resolution magnetic resonance imaging (MRI) scans were automatically processed combining cytoarchitectonically defined probabilistic maps with advanced tissue segmentation and registration methods. Overall, we observed steeper negative regression slopes in controls. The analysis further revealed a significant group-by-age interaction for the left subiculum with a significant negative correlation between age and subicular volume in controls, but no significant correlation in meditators. Altogether, these findings seem to suggest a reduced age-related atrophy of the left subiculum in meditators compared to healthy controls. Possible explanations might be a relative increase of subicular tissue over time through long-term training as meditation is a process that incorporates regular and ongoing mental efforts. Alternatively, because meditation is an established form of reducing stress, our observation might reflect an overall preservation of subicular tissue through a reduced neuronal vulnerability to negative effects of stress. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. [Establishment of oxygen and glucose deprive model of in vitro cultured hippocampal neuron and effect of ligustrazine on intracellular Ca+ level in model neurons].

    Science.gov (United States)

    Wan, Hai-tong; Wang, Yu; Yang, Jie-hong

    2007-03-01

    To establish the oxygen and glucose deprive (OGD) model in cultured hippocampal neuron and study the effect of ligustrazine on intracellular Ca2+ level in the model neurons. The OGD model was established in cultured hippocampal neuron, and the intracellular Ca2+ level in it was detected by laser scanning confocal microscope (LSCM). The OGD model was successfully established in cultured hippocampal neurons; the intracellular Ca2+ level in the OGD model group was significantly higher than that in the blank control group (P neuron, which could be antagonized by ligustrazine, indicating that ligustrazine has a protective effect on hippocampal neuron from hypoxic-ischemic injury.

  12. Sociosexual and communication deficits after traumatic injury to the developing murine brain.

    Directory of Open Access Journals (Sweden)

    Bridgette D Semple

    Full Text Available Despite the life-long implications of social and communication dysfunction after pediatric traumatic brain injury, there is a poor understanding of these deficits in terms of their developmental trajectory and underlying mechanisms. In a well-characterized murine model of pediatric brain injury, we recently demonstrated that pronounced deficits in social interactions emerge across maturation to adulthood after injury at postnatal day (p 21, approximating a toddler-aged child. Extending these findings, we here hypothesized that these social deficits are dependent upon brain maturation at the time of injury, and coincide with abnormal sociosexual behaviors and communication. Age-dependent vulnerability of the developing brain to social deficits was addressed by comparing behavioral and neuroanatomical outcomes in mice injured at either a pediatric age (p21 or during adolescence (p35. Sociosexual behaviors including social investigation and mounting were evaluated in a resident-intruder paradigm at adulthood. These outcomes were complemented by assays of urine scent marking and ultrasonic vocalizations as indices of social communication. We provide evidence of sociosexual deficits after brain injury at p21, which manifest as reduced mounting behavior and scent marking towards an unfamiliar female at adulthood. In contrast, with the exception of the loss of social recognition in a three-chamber social approach task, mice that received TBI at adolescence were remarkably resilient to social deficits at adulthood. Increased emission of ultrasonic vocalizations (USVs as well as preferential emission of high frequency USVs after injury was dependent upon both the stimulus and prior social experience. Contrary to the hypothesis that changes in white matter volume may underlie social dysfunction, injury at both p21 and p35 resulted in a similar degree of atrophy of the corpus callosum by adulthood. However, loss of hippocampal tissue was greater after p21

  13. Hippocampal volume reduction in congenital central hypoventilation syndrome.

    Directory of Open Access Journals (Sweden)

    Paul M Macey

    Full Text Available Children with congenital central hypoventilation syndrome (CCHS, a genetic disorder characterized by diminished drive to breathe during sleep and impaired CO(2 sensitivity, show brain structural and functional changes on magnetic resonance imaging (MRI scans, with impaired responses in specific hippocampal regions, suggesting localized injury.We assessed total volume and regional variation in hippocampal surface morphology to identify areas affected in the syndrome. We studied 18 CCHS (mean age+/-std: 15.1+/-2.2 years; 8 female and 32 healthy control (age 15.2+/-2.4 years; 14 female children, and traced hippocampi on 1 mm(3 resolution T1-weighted scans, collected with a 3.0 Tesla MRI scanner. Regional hippocampal volume variations, adjusted for cranial volume, were compared between groups based on t-tests of surface distances to the structure midline, with correction for multiple comparisons. Significant tissue losses emerged in CCHS patients on the left side, with a trend for loss on the right; however, most areas affected on the left also showed equivalent right-sided volume reductions. Reduced regional volumes appeared in the left rostral hippocampus, bilateral areas in mid and mid-to-caudal regions, and a dorsal-caudal region, adjacent to the fimbria.The volume losses may result from hypoxic exposure following hypoventilation during sleep-disordered breathing, or from developmental or vascular consequences of genetic mutations in the syndrome. The sites of change overlap regions of abnormal functional responses to respiratory and autonomic challenges. Affected hippocampal areas have roles associated with memory, mood, and indirectly, autonomic regulation; impairments in these behavioral and physiological functions appear in CCHS.

  14. Implantation of Neuronal Stem Cells Enhances Object Recognition without Increasing Neurogenesis after Lateral Fluid Percussion Injury in Mice

    Directory of Open Access Journals (Sweden)

    Laura B. Ngwenya

    2018-01-01

    Full Text Available Cognitive deficits after traumatic brain injury (TBI are debilitating and contribute to the morbidity and loss of productivity of over 10 million people worldwide. Cell transplantation has been linked to enhanced cognitive function after experimental traumatic brain injury, yet the mechanism of recovery is poorly understood. Since the hippocampus is a critical structure for learning and memory, supports adult neurogenesis, and is particularly vulnerable after TBI, we hypothesized that stem cell transplantation after TBI enhances cognitive recovery by modulation of endogenous hippocampal neurogenesis. We performed lateral fluid percussion injury (LFPI in adult mice and transplanted embryonic stem cell-derived neural progenitor cells (NPC. Our data confirm an injury-induced cognitive deficit in novel object recognition, a hippocampal-dependent learning task, which is reversed one week after NPC transplantation. While LFPI alone promotes hippocampal neurogenesis, as revealed by doublecortin immunolabeling of immature neurons, subsequent NPC transplantation prevents increased neurogenesis and is not associated with morphological maturation of endogenous injury-induced immature neurons. Thus, NPC transplantation enhances cognitive recovery early after LFPI without a concomitant increase in neuron numbers or maturation.

  15. Correlation of clinical course with MRI findings in olivo-pontocerebellar atrophy and late-cortical cerebellar atrophy

    International Nuclear Information System (INIS)

    Konagaya, Masaaki; Morishita, Shinji; Konagaya, Yoko; Takayanagi, Tetsuya; Iwasaki, Satoru

    1989-01-01

    We quantitatively analyzed 1.5 T MRI in 36 cases of sporadic spinocerebellar degeneration (SCD) and 30 control cases without intracranial lesions, using graphic analyzer. SCD consisted of 21 olivo-ponto-cerebellar atrophy (OPCA) and 15 late cortical cerebellar atrophy (LCCA). There was negative correlation between vermian size and the duration of illness both in OPCA (r=0.8960, p<0.001) and LCCA (r=0.7756, p<0.01), but the progression rate in OPCA was three times greater than that in LCCA. LCCA was suggested the preclinical vermian atrophy by the statistical regression study. In OPCA, the duration of illness also revealed significant correlations with atrophy of ventral pons (r=0.8308, p<0.001) and also cerebellar hemisphere (medial hemiphere; r=0.7278, p<0.001. lateral hemisphere; r=0.6039, p<0.01). OPCA showed diffuse atrophy of cerebellar hemisphere, whereas LCCA showed medial dominant atrophy. OPCA demonstrated significant correlation between the fourth ventricle dilatation and the duration of illness (r=0.6005, p<0.01). A discriminant study significantly separated OPCA, LCCA and control each other by sizes of ventral pons and cerebellar vermis (p<0.001). In T2 weighted MRI, 10 cases out of 14 LCCA did not show hypointensity in dentate nucleus in spite of normal appearance in the other portions usually decreased intensity. The dentate nucleus of OPCA showed a significant atrophy. The insidence of putaminal hypointensity in OPCA was significantly greater than that of control group (ki-quare=6.476, p<0.05). There were no atrophies in red nucleus and tegmentum of midbrain, which indicated minimum involvement in cerebellar efferent system both in OPCA and LCCA. We concluded that the quantitative and qualitative analysis of high field MRI is useful in clinical discrimination between OPCA and LCCA. (author)

  16. [Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis].

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  17. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis.

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  18. Prognostic analysis of 216 cases with penetrating ocular injury

    Directory of Open Access Journals (Sweden)

    Yong Guo

    2013-08-01

    Full Text Available AIM: To analyze the factors of penetrating ocular injury, and to investigate the prognostic factors and treatment strategies. METHODS: A retrospective analysis of 216 ocular trauma patients(221 eyes, in our hospital from November 2009 to November 2011, was completed. RESULTS: The eyeball atrophy inevitably occurred in 13 eye wounds more than 30mm. Retinal prolapse of the eyes, 78%(35/45completed vitrectomy, 33%(15/45were eyeball atrophy. The 51%(20/39of subchoroidal hemorrhage eyes were eyeball atrophy. Retinal prolapse and subchoroidal hemorrhage increased the risk of ocular atrophy(PPCONCLUSION: Serious ocular trauma prognosis related to many factors. The retina prolapse and the subchoroidal hemorrhage were important prognosis testify. A scleral buckling condensation surgery and vitrectomy have a therapeutic effect, and can improve visual function.

  19. Impaired Skin Barrier Due to Sebaceous Gland Atrophy in the Latent Stage of Radiation-Induced Skin Injury: Application of Non-Invasive Diagnostic Methods

    Directory of Open Access Journals (Sweden)

    Hyosun Jang

    2018-01-01

    Full Text Available Radiation-induced skin injury can take the form of serious cutaneous damage and have specific characteristics. Asymptomatic periods are classified as the latent stage. The skin barrier plays a critical role in the modulation of skin permeability and hydration and protects the body against a harsh external environment. However, an analysis on skin barrier dysfunction against radiation exposure in the latent stage has not been conducted. Thus, we investigated whether the skin barrier is impaired by irradiation in the latent stage and aimed to identify the molecules involved in skin barrier dysfunction. We analyzed skin barrier function and its components in SKH1 mice that received 20 and 40 Gy local irradiation. Increased transepidermal water loss and skin pH were observed in the latent stage of the irradiated skin. Skin barrier components, such as structural proteins and lipid synthesis enzymes in keratinocyte, increased in the irradiated group. Interestingly, we noted sebaceous gland atrophy and increased serine protease and inflammatory cytokines in the irradiated skin during the latent period. This finding indicates that the main factor of skin barrier dysfunction in the latent stage of radiation-induced skin injury is sebaceous gland deficiency, which could be an intervention target for skin barrier impairment.

  20. Genetics Home Reference: optic atrophy type 1

    Science.gov (United States)

    ... Nerve Atrophy Encyclopedia: Visual Acuity Test Health Topic: Color Blindness Health Topic: Optic Nerve Disorders Genetic and Rare ... Disease InfoSearch: Optic atrophy 1 Kids Health: What's Color Blindness? MalaCards: autosomal dominant optic atrophy, classic form Merck ...

  1. Long-term consequences of a prolonged febrile seizure in a dual pathology model.

    Science.gov (United States)

    Gibbs, Steve; Chattopadhyaya, Bidisha; Desgent, Sébastien; Awad, Patricia N; Clerk-Lamalice, Olivier; Levesque, Maxime; Vianna, Rose-Mari; Rébillard, Rose-Marie; Delsemme, Andrée-Anne; Hébert, David; Tremblay, Luc; Lepage, Martin; Descarries, Laurent; Di Cristo, Graziella; Carmant, Lionel

    2011-08-01

    Clinical evidence suggests that febrile status epilepticus (SE) in children can lead to acute hippocampal injury and subsequent temporal lobe epilepsy. The contribution of febrile SE to the mechanisms underlying temporal lobe epilepsy are however poorly understood. A rat model of temporal lobe epilepsy following hyperthermic SE was previously established in our laboratory, wherein a focal cortical lesion induced at postnatal day 1 (P1), followed by a hyperthermic SE (more than 30 min) at P10, leads to hippocampal atrophy at P22 (dual pathology model) and spontaneous recurrent seizures (SRS) with mild visuospatial memory deficits in adult rats. The goal of this study was to identify the long term electrophysiological, anatomical and molecular changes in this model. Following hyperthermic SE, all cortically lesioned pups developed progressive SRS as adults, characterized by the onset of highly rhythmic activity in the hippocampus. A reduction of hippocampal volume on the side of the lesion preceded the SRS and was associated with a loss of hippocampal neurons, a marked decrease in pyramidal cell spine density, an increase in the hippocampal levels of NMDA receptor NR2A subunit, but no significant change in GABA receptors. These findings suggest that febrile SE in the abnormal brain leads to hippocampal injury that is followed by progressive network reorganization and molecular changes that contribute to the epileptogenesis as well as the observed memory deficits. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Anti-skeletal muscle atrophy effect of Oenothera odorata root extract via reactive oxygen species-dependent signaling pathways in cellular and mouse model.

    Science.gov (United States)

    Lee, Yong-Hyeon; Kim, Wan-Joong; Lee, Myung-Hun; Kim, Sun-Young; Seo, Dong-Hyun; Kim, Han-Sung; Gelinsky, Michael; Kim, Tack-Joong

    2016-01-01

    Skeletal muscle atrophy can be defined as a decrease of muscle volume caused by injury or lack of use. This condition is associated with reactive oxygen species (ROS), resulting in various muscular disorders. We acquired 2D and 3D images using micro-computed tomography in gastrocnemius and soleus muscles of sciatic-denervated mice. We confirmed that sciatic denervation-small animal model reduced muscle volume. However, the intraperitoneal injection of Oenothera odorata root extract (EVP) delayed muscle atrophy compared to a control group. We also investigated the mechanism of muscle atrophy's relationship with ROS. EVP suppressed expression of SOD1, and increased expression of HSP70, in both H2O2-treated C2C12 myoblasts and sciatic-denervated mice. Moreover, EVP regulated apoptotic signals, including caspase-3, Bax, Bcl-2, and ceramide. These results indicate that EVP has a positive effect on reducing the effect of ROS on muscle atrophy.

  3. Long-term global and regional brain volume changes following severe traumatic brain injury: A longitudinal study with clinical correlates

    DEFF Research Database (Denmark)

    Sidaros, Annette; Skimminge, Arnold Jesper Møller; Liptrot, Matthew George

    2009-01-01

    with percent brain volume change (%BVC) ranging between − 0.6% and − 9.4% (mean − 4.0%). %BVC correlated significantly with injury severity, functional status at both scans, and with 1-year outcome. Moreover, %BVC improved prediction of long-term functional status over and above what could be predicted using......Traumatic brain injury (TBI) results in neurodegenerative changes that progress for months, perhaps even years post-injury. However, there is little information on the spatial distribution and the clinical significance of this late atrophy. In 24 patients who had sustained severe TBI we acquired 3D...... scan time point using SIENAX. Regional distribution of atrophy was evaluated using tensor-based morphometry (TBM). At the first scan time point, brain parenchymal volume was reduced by mean 8.4% in patients as compared to controls. During the scan interval, patients exhibited continued atrophy...

  4. Combination of MRI hippocampal volumetry and arterial spin labeling MR perfusion at 3-Tesla improves the efficacy in discriminating Alzheimer's disease from cognitively normal elderly adults.

    Science.gov (United States)

    Mak, Henry Ka-Fung; Qian, Wenshu; Ng, Kwok Sing; Chan, Queenie; Song, You-Qiang; Chu, Leung Wing; Yau, Kelvin Kai-Wing

    2014-01-01

    Structural magnetic resonance imaging has been employed for evaluation of medial temporal atrophy in patients with Alzheimer's disease (AD). Arterial spin labeling (ASL) technique could detect cerebral perfusion abnormalities in AD. We hypothesized that combination of hippocampal volumetry and cerebral blood flow yield higher accuracy than either method alone in discriminating AD patients from cognitively normal elderly adults. 13 AD patients and 15 healthy controls were studied using a 3-tesla scanner. Standardized T1W 3D volumetric Fast Field Echo and QUASAR ASL sequences were employed for cerebral volumetry and perfusion respectively. Manual Right and left hippocampal volumetry was performed manually by ANALYZE software, with total intracranial volume normalization. ASL data were analyzed by institutional specially-design software to calculate cerebral blood flow of region-of-interests placed at the middle and posterior cingulate gyri. Right and left hippocampal volumes and middle and posterior cingulate gyri cerebral blood flows were significantly lower in the patients than in the controls (independent-samples t-tests, p volumetry and cerebral perfusion has improved efficacy in discriminating AD patients from cognitively normal elderly adults.

  5. Practical one-dimensional measurements of age-related brain atrophy are validated by 3-dimensional values and clinical outcomes: a retrospective study

    International Nuclear Information System (INIS)

    Dunham, C. Michael; Cook, Albert J. II; Paparodis, Alaina M.; Huang, Gregory S.

    2016-01-01

    validity of these methods is also supported by their association with post-injury ICH. Intracranial 3-D software is not available on many CT scanners and can be cumbersome, when available. Simple 1-D measurements, using the study methodology, are a practical method to objectify the presence of age-related brain atrophy

  6. The inheritance of peripapillary atrophy

    NARCIS (Netherlands)

    Healey, Paul R.; Mitchell, Paul; Gilbert, Clare E.; Lee, Anne J.; Ge, Dongliang; Snieder, Harold; Spector, Timothy D.; Hammond, Christopher J.

    PURPOSE. To estimate the relative importance of genes and environment in peripapillary atrophy type beta (beta-PPA) in a classic twin study. METHODS. Female twin pairs (n = 506) aged 49 to 79 years were recruited from the St. Thomas' UK Adult Twin Registry. Peripapillary atrophy was identified from

  7. Bayesian longitudinal segmentation of hippocampal substructures in brain MRI using subject-specific atlases.

    Science.gov (United States)

    Iglesias, Juan Eugenio; Van Leemput, Koen; Augustinack, Jean; Insausti, Ricardo; Fischl, Bruce; Reuter, Martin

    2016-11-01

    The hippocampal formation is a complex, heterogeneous structure that consists of a number of distinct, interacting subregions. Atrophy of these subregions is implied in a variety of neurodegenerative diseases, most prominently in Alzheimer's disease (AD). Thanks to the increasing resolution of MR images and computational atlases, automatic segmentation of hippocampal subregions is becoming feasible in MRI scans. Here we introduce a generative model for dedicated longitudinal segmentation that relies on subject-specific atlases. The segmentations of the scans at the different time points are jointly computed using Bayesian inference. All time points are treated the same to avoid processing bias. We evaluate this approach using over 4700 scans from two publicly available datasets (ADNI and MIRIAD). In test-retest reliability experiments, the proposed method yielded significantly lower volume differences and significantly higher Dice overlaps than the cross-sectional approach for nearly every subregion (average across subregions: 4.5% vs. 6.5%, Dice overlap: 81.8% vs. 75.4%). The longitudinal algorithm also demonstrated increased sensitivity to group differences: in MIRIAD (69 subjects: 46 with AD and 23 controls), it found differences in atrophy rates between AD and controls that the cross sectional method could not detect in a number of subregions: right parasubiculum, left and right presubiculum, right subiculum, left dentate gyrus, left CA4, left HATA and right tail. In ADNI (836 subjects: 369 with AD, 215 with early cognitive impairment - eMCI - and 252 controls), all methods found significant differences between AD and controls, but the proposed longitudinal algorithm detected differences between controls and eMCI and differences between eMCI and AD that the cross sectional method could not find: left presubiculum, right subiculum, left and right parasubiculum, left and right HATA. Moreover, many of the differences that the cross-sectional method already found

  8. Cerebral atrophy in Parkinson's disease - represented in CT

    International Nuclear Information System (INIS)

    Becker, H.; Schneider, E.; Hacker, H.; Fischer, P.A.; Frankfurt Univ.

    1979-01-01

    To clarify the importance of brain atrophy in relation to the symptoms of Parkinson's disease, 173 patients were examined by computed tomography (CT). In 51.4% of the CT findings, brain atrophy was considered to be pathological. Statistically significant relations of age and sex were found with regard to the extent and localization of brain atrophy. Cortical atrophy also showed a significant dependence on duration of disease. Linear measurements at the lateral ventricles and the third ventricle lead us to assume that brain atrophy in Parkinson's patients is more prevalent than in normal patients within the scope of age involution. (orig.)

  9. Cerebral atrophy in Parkinson's disease - represented in CT

    Energy Technology Data Exchange (ETDEWEB)

    Becker, H; Schneider, E; Hacker, H; Fischer, P A [Frankfurt Univ. (Germany, F.R.). Abt. fuer Neuroradiologie; Frankfurt Univ. (Germany, F.R.). Abt. fuer Neurologie)

    1979-01-01

    To clarify the importance of brain atrophy in relation to the symptoms of Parkinson's disease, 173 patients were examined by computed tomography (CT). In 51.4% of the CT findings, brain atrophy was considered to be pathological. Statistically significant relations of age and sex were found with regard to the extent and localization of brain atrophy. Cortical atrophy also showed a significant dependence on duration of disease. Linear measurements at the lateral ventricles and the third ventricle lead us to assume that brain atrophy in Parkinson's patients is more prevalent than in normal patients within the scope of age involution.

  10. Usefulness of single voxel proton MR spectroscopy in the evaluation of hippocampal sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Kee Hyun; Kim, Hong Dae; Park, Sun Won; Song, In Chan; Yu, In Kyu; Han, Moon Hee; Lee, Sang Kun; Chung, Chun Kee; Park, Yang Hee [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2000-03-01

    The purpose of our study was to determine the ability of H-1 MR spectroscopy (MRS) to lateralize the lesion in patients with hippocampal scleros is. Twenty healthy volunteers and 25 patients with intractable temporal lobe epilepsy whose MR imaging diagnosis was unilateral hippocampal sclerosis were included. This diagnosis was based on the presence of unilateral atrophy and/or high T2 signal intensity of the hippocampus. Singlevoxel H-1 MRS was carried out on a 1.5-T unit using PRESS sequence (TE, 136 msec). Spectra were obtained from hippocampal areas bilaterally with volumes of interest (VOIs) of 6.0 cm{sup 3} and 2.25 cm{sup 3} in healthy volunteers, and of either 6.0 c m{sup 3} (n = 14) or 2.25 cm{sup 3} (n = 11) in patients. Metabolite ratios of NAA/Cho and NAA/Cr were calculated from relative peak height measurements. The capability of MRS to lateralize the lesion and to detect bilateral abnormalities was compared with MR imaging diagnosis as a standard of reference. In healthy volunteers, NAA/Cho and NAA/Cr ratios were greater than 0.8 and 1.0, respectively. In patients, the mean values of these ratios were significantly lower on the lesion side than on the contralateral side, and lower than those of healthy volunteers (p <.05). The overall correct lateralization rate of MRS was 72% (18/25); this rate was lower with a VOI of 6.0 cm{sup 3} than of 2.25 cm{sup 3} (64% versus 82%, p <.05). Bilateral abnormalities on MRS were found in 24% (6/25) of cases. Although its rate of correct lateralization is low, single-voxel H-1 MRS is a useful and promising diagnostic tool in the evaluation of hippocampal sclerosis, particularly for the detection of bilateral abnormalities. To improve the diagnostic accuracy of H-1 MRS, further investigation, including the use of a smaller VOI and measurement of the absolute amount of metabolites, are needed.

  11. Genetics Home Reference: spinal muscular atrophy

    Science.gov (United States)

    ... difficulty breathing. Children with this type often have joint deformities (contractures) that impair movement. In severe cases, ... Proximal spinal muscular atrophy Washington University, St. Louis: Neuromuscular Disease Center: Spinal Muscular Atrophy Patient Support and ...

  12. Effect of sevoflurane on the ATPase activity of hippocampal neurons in a rat model of cerebral ischemia-reperfusion injury via the cAMP-PKA signaling pathway.

    Science.gov (United States)

    Liu, Tie-Jun; Zhang, Jin-Cun; Gao, Xiao-Zeng; Tan, Zhi-Bin; Wang, Jian-Jun; Zhang, Pan-Pan; Cheng, Ai-Bin; Zhang, Shu-Bo

    2018-01-01

    We aim to investigate the effects of sevoflurane on the ATPase activity of the hippocampal neurons in rats with cerebral ischemia-reperfusion injury (IRI) via the cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) signaling pathway. Sixty rats were assigned into the normal, model and sevoflurane groups (n = 20, the latter two groups were established as focal cerebral IRI models). The ATPase activity was detected using an ultramicro Na (+)-K (+)-ATP enzyme kit. Immunohistochemical staining was used to detect the positive protein expression of cAMP and PKA. The hippocampal neurons were assigned to the normal, IRI, IRI + sevoflurane, IRI + forskolin, IRI + H89 and IRI + sevoflurane + H89 groups. qRT-PCR and Western blotting were performed for the expressions of cAMP, PKA, cAMP-responsive element-binding protein (CREB) and brain derived neurotrophic factor (BDNF). The normal and sevoflurane groups exhibited a greater positive protein expression of cAMP and PKA than the model group. Compared with the normal group, the expressions of cAMP, PKA, CREB and BDNF all reduced in the IRI, model and IRI + H89 groups. The sevoflurane group showed higher cAMP, PKA, CREB and BDNF expressions than the model group. Compared with the IRI group, ATPase activity and expressions of cAMP, PKA, CREB and BDNF all increased in the normal, IRI + sevoflurane and IRI + forskolin groups but decreased in the IRI + H89 group. It suggests that sevoflurane could enhance ATPase activity in hippocampal neurons of cerebral IRI rats through activating cAMP-PKA signaling pathway. Copyright © 2017. Published by Elsevier Taiwan.

  13. Follow-up CT myelography of severe cervical spinal cord injury

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Keiichi; Onoda, Kimio; Kawashima, Yasuhiro; Muto, Atsushi; Kobayashi, Yoichi

    1987-11-01

    There are many reports describing gross anatomical and microscopical findings of severely injured cervical cords in autopsy of the acute and chronic state, but no morphological findings of a severe cervical spinal cord injury in a chronic state by follow-up CT myelography have been found in the literature so far. The sagittal and transverse diameters of the cervical spinal cord and subarachnoid space of 9 out of 14 severe cervical spinal cord injury patients were measured with CT myelography within 7.5 years after the tranuma and their size compared with a control group which was made up of 29 patients with slight radiculopathy due to cervical spondylosis and whiplash injuries. Injured cord levels were C4 4 cases, C5 4 cases and C6 1 case. Remarkable spinal cord atrophy was recogniged in the sagittal diameter from C1 to C7 and in the transverse diameter below C4 and narrowing of the cervical subarachnoid space in the sagittal diameter from C2 to C5. The significance level was set at 1 - 5 %. From these fingings, we have concluded that atrophy appeared not only in the injured segment but also the whole cervical cord after the trauma. There was less cord atrophy in a good functional prognosis than in a poor prognosis.

  14. Follow-up CT myelography of severe cervical spinal cord injury

    International Nuclear Information System (INIS)

    Okada, Keiichi; Onoda, Kimio; Kawashima, Yasuhiro; Muto, Atsushi; Kobayashi, Yoichi

    1987-01-01

    There are many reports describing gross anatomical and microscopical findings of severely injured cervical cords in autopsy of the acute and chronic state, but no morphological findings of a severe cervical spinal cord injury in a chronic state by follow-up CT myelography have been found in the literature so far. The sagittal and transverse diameters of the cervical spinal cord and subarachnoid space of 9 out of 14 severe cervical spinal cord injury patients were measured with CT myelography within 7.5 years after the tranuma and their size compared with a control group which was made up of 29 patients with slight radiculopathy due to cervical spondylosis and whiplash injuries. Injured cord levels were C4 4 cases, C5 4 cases and C6 1 case. Remarkable spinal cord atrophy was recogniged in the sagittal diameter from C1 to C7 and in the transverse diameter below C4 and narrowing of the cervical subarachnoid space in the sagittal diameter from C2 to C5. The significance level was set at 1 - 5 %. From these fingings, we have concluded that atrophy appeared not only in the injured segment but also the whole cervical cord after the trauma. There was less cord atrophy in a good functional prognosis than in a poor prognosis. (author)

  15. A grading system for hippocampal sclerosis based on the degree of hippocampal mossy fiber sprouting

    NARCIS (Netherlands)

    Gispen, W.H.; Proper, E.A.; Jansen, G.H.; Veelen, C.W. van; Rijen, P.C. van; Graan, P.N.E. de

    2001-01-01

    Abstract. In patients suffering from temporal lobe epilepsy (TLE) a highly variable degree of hippocampal sclerosis (HS) can be observed. For standard neuropathological evaluation after hippocampal resection, neuronal cell loss in the hippocampal subareas is assessed (Wyler score 0-4) [Wyler et al.

  16. Moderate injury in motor-sensory cortex causes behavioral deficits accompanied by electrophysiological changes in mice adulthood.

    Directory of Open Access Journals (Sweden)

    Wei Ouyang

    Full Text Available Moderate traumatic brain injury (TBI in children often happen when there's a sudden blow to the frontal bone, end with long unconscious which can last for hours and progressive cognitive deficits. However, with regard to the influences of moderate TBI during children adulthood, injury-induced alterations of locomotive ability, long-term memory performance, and hippocampal electrophysiological firing changes have not yet been fully identified. In this study, lateral fluid percussion (LFP method was used to fabricate moderate TBI in motor and somatosensory cortex of the 6-weeks-old mice. The motor function, learning and memory function, extracellular CA1 neural spikes were assessed during acute and subacute phase. Moreover, histopathology was performed on day post injury (DPI 16 to evaluate the effect of TBI on tissue and cell morphological changes in cortical and hippocampal CA1 subregions. After moderate LFP injury, the 6-weeks-old mice showed severe motor deficits at the early stage in acute phase but gradually recovered later during adulthood. At the time points in acute and subacute phase after TBI, novel object recognition (NOR ability and spatial memory functions were consistently impaired in TBI mice; hippocampal firing frequency and burst probability were hampered. Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop. These electrophysiological impacts were associated with substantially lowered NOR preference as compared to the sham group during adulthood. These results suggest that moderate TBI introduced at motorsenory cortex in 6-weeks-old mice causes obvious motor and cognitive deficits during their adulthood. While the locomotive ability progressively recovers, the cognitive deficits persisted while the mice mature as adult mice. The cognitive deficits may be attributed to the general suppressing of whole neural network, which could be labeled by marked reduction of excitability in hippocampal CA1

  17. Moderate injury in motor-sensory cortex causes behavioral deficits accompanied by electrophysiological changes in mice adulthood.

    Science.gov (United States)

    Ouyang, Wei; Yan, Qichao; Zhang, Yu; Fan, Zhiheng

    2017-01-01

    Moderate traumatic brain injury (TBI) in children often happen when there's a sudden blow to the frontal bone, end with long unconscious which can last for hours and progressive cognitive deficits. However, with regard to the influences of moderate TBI during children adulthood, injury-induced alterations of locomotive ability, long-term memory performance, and hippocampal electrophysiological firing changes have not yet been fully identified. In this study, lateral fluid percussion (LFP) method was used to fabricate moderate TBI in motor and somatosensory cortex of the 6-weeks-old mice. The motor function, learning and memory function, extracellular CA1 neural spikes were assessed during acute and subacute phase. Moreover, histopathology was performed on day post injury (DPI) 16 to evaluate the effect of TBI on tissue and cell morphological changes in cortical and hippocampal CA1 subregions. After moderate LFP injury, the 6-weeks-old mice showed severe motor deficits at the early stage in acute phase but gradually recovered later during adulthood. At the time points in acute and subacute phase after TBI, novel object recognition (NOR) ability and spatial memory functions were consistently impaired in TBI mice; hippocampal firing frequency and burst probability were hampered. Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop. These electrophysiological impacts were associated with substantially lowered NOR preference as compared to the sham group during adulthood. These results suggest that moderate TBI introduced at motorsenory cortex in 6-weeks-old mice causes obvious motor and cognitive deficits during their adulthood. While the locomotive ability progressively recovers, the cognitive deficits persisted while the mice mature as adult mice. The cognitive deficits may be attributed to the general suppressing of whole neural network, which could be labeled by marked reduction of excitability in hippocampal CA1 subregion.

  18. Hippocampal adaptive response following extensive neuronal loss in an inducible transgenic mouse model.

    Directory of Open Access Journals (Sweden)

    Kristoffer Myczek

    Full Text Available Neuronal loss is a common component of a variety of neurodegenerative disorders (including Alzheimer's, Parkinson's, and Huntington's disease and brain traumas (stroke, epilepsy, and traumatic brain injury. One brain region that commonly exhibits neuronal loss in several neurodegenerative disorders is the hippocampus, an area of the brain critical for the formation and retrieval of memories. Long-lasting and sometimes unrecoverable deficits caused by neuronal loss present a unique challenge for clinicians and for researchers who attempt to model these traumas in animals. Can these deficits be recovered, and if so, is the brain capable of regeneration following neuronal loss? To address this significant question, we utilized the innovative CaM/Tet-DT(A mouse model that selectively induces neuronal ablation. We found that we are able to inflict a consistent and significant lesion to the hippocampus, resulting in hippocampally-dependent behavioral deficits and a long-lasting upregulation in neurogenesis, suggesting that this process might be a critical part of hippocampal recovery. In addition, we provide novel evidence of angiogenic and vasculature changes following hippocampal neuronal loss in CaM/Tet-DTA mice. We posit that angiogenesis may be an important factor that promotes neurogenic upregulation following hippocampal neuronal loss, and both factors, angiogenesis and neurogenesis, can contribute to the adaptive response of the brain for behavioral recovery.

  19. Non-invasive assessment of radiation injury with electrical impedance spectroscopy

    International Nuclear Information System (INIS)

    Osterman, K Sunshine; Hoopes, P Jack; De Lorenzo, Christine; Gladstone, David J; Paulsen, Keith D

    2004-01-01

    A detailed understanding of non-targeted normal tissue response is necessary for the optimization of radiation treatment plans in cancer therapy. In this study, we evaluate the ability of electrical impedance spectroscopy (EIS) to non-invasively determine and quantify the injury response in soft tissue after high dose rate (HDR) irradiation, which is characterized by large localized dose distributions possessing steep spatial gradients. The HDR after-loading technique was employed to irradiate small volumes of muscle tissue with single doses (26-52 Gy targeted 5 mm away from the source). Impedance measurements were performed on 29 rats at 1, 2 and 3 month post-irradiation, employing 31 frequencies in the 1 kHz to 1 MHz range. Over the first 3 months, conductivity increased by 48% and 26% following target doses of 52 Gy and 26 Gy 5 mm from the HDR source, respectively. Injury, assessed independently through a grid-based scoring method showed a quadratic dependence on distance from source. A significant injury (50% of cells atrophied, necrotic or degenerating) in 1.2% of the volume, accompanied by more diffuse injury (25% of cells atrophied, necrotic or degenerating) in 9% of the tissue produced a conductivity increase of 0.02 S m -1 (8% over a baseline of 0.24 S m -1 ). This was not statistically significant at p 0.01. Among treatment groups, injury differences in 22% of the volume led to statistically significant differences in conductivity of 0.07 S m -1 (23% difference in conductivity). Despite limitations, the success of EIS in detecting responses in a fraction of the tissue probed, during these early post-irradiation time-points, is encouraging. Electrical impedance spectroscopy may provide a useful metric of atrophy and the development of fibrosis secondary to radiation that could be further developed into a low-cost imaging method for radiotherapy monitoring and assessment

  20. Sustained Na+/H+ exchanger activation promotes gliotransmitter release from reactive hippocampal astrocytes following oxygen-glucose deprivation.

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    Pelin Cengiz

    Full Text Available Hypoxia ischemia (HI-related brain injury is the major cause of long-term morbidity in neonates. One characteristic hallmark of neonatal HI is the development of reactive astrogliosis in the hippocampus. However, the impact of reactive astrogliosis in hippocampal damage after neonatal HI is not fully understood. In the current study, we investigated the role of Na(+/H(+ exchanger isoform 1 (NHE1 protein in mouse reactive hippocampal astrocyte function in an in vitro ischemia model (oxygen/glucose deprivation and reoxygenation, OGD/REOX. 2 h OGD significantly increased NHE1 protein expression and NHE1-mediated H(+ efflux in hippocampal astrocytes. NHE1 activity remained stimulated during 1-5 h REOX and returned to the basal level at 24 h REOX. NHE1 activation in hippocampal astrocytes resulted in intracellular Na(+ and Ca(2+ overload. The latter was mediated by reversal of Na(+/Ca(2+ exchange. Hippocampal astrocytes also exhibited a robust release of gliotransmitters (glutamate and pro-inflammatory cytokines IL-6 and TNFα during 1-24 h REOX. Interestingly, inhibition of NHE1 activity with its potent inhibitor HOE 642 not only reduced Na(+ overload but also gliotransmitter release from hippocampal astrocytes. The noncompetitive excitatory amino acid transporter inhibitor TBOA showed a similar effect on blocking the glutamate release. Taken together, we concluded that NHE1 plays an essential role in maintaining H(+ homeostasis in hippocampal astrocytes. Over-stimulation of NHE1 activity following in vitro ischemia disrupts Na(+ and Ca(2+ homeostasis, which reduces Na(+-dependent glutamate uptake and promotes release of glutamate and cytokines from reactive astrocytes. Therefore, blocking sustained NHE1 activation in reactive astrocytes may provide neuroprotection following HI.

  1. Seronegative Intestinal Villous Atrophy: A Diagnostic Challenge

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    Cláudio Martins

    2016-01-01

    Full Text Available Celiac disease is the most important cause of intestinal villous atrophy. Seronegative intestinal villous atrophy, including those that are nonresponsive to a gluten-free diet, is a diagnostic challenge. In these cases, before establishing the diagnosis of seronegative celiac disease, alternative etiologies of atrophic enteropathy should be considered. Recently, a new clinical entity responsible for seronegative villous atrophy was described—olmesartan-induced sprue-like enteropathy. Herein, we report two uncommon cases of atrophic enteropathy in patients with arterial hypertension under olmesartan, who presented with severe chronic diarrhea and significant involuntary weight loss. Further investigation revealed intestinal villous atrophy and intraepithelial lymphocytosis. Celiac disease and other causes of villous atrophy were ruled out. Drug-induced enteropathy was suspected and clinical improvement and histologic recovery were verified after olmesartan withdrawal. These cases highlight the importance for clinicians to maintain a high index of suspicion for olmesartan as a precipitant of sprue-like enteropathy.

  2. Delayed rectifier potassium channels are involved in SO2 derivative-induced hippocampal neuronal injury.

    Science.gov (United States)

    Li, Guangke; Sang, Nan

    2009-01-01

    Recent studies implicate the possible neurotoxicity of SO(2), however, its mechanisms remain unclear. In the present study, we investigated SO(2) derivative-induced effect on delayed rectifier potassium channels (I(K)) and cellular death/apoptosis in primary cultured hippocampal neurons. The results demonstrate that SO(2) derivatives (NaHSO(3) and Na(2)SO(3), 3:1M/M) effectively augmented I(K) and promoted the activation of delayed rectifier potassium channels. Also, SO(2) derivatives increased neuronal death percentage and contributed to the formation of DNA ladder in concentration-dependent manners. Interestingly, the neuronal death and DNA ladder formation, caused by SO(2) derivatives, could be attenuated by the delayed rectifier potassium channel blocker (tetraethylammonium, TEA), but not by the transient outward potassium channel blocker (4-aminopyridine, 4-AP). It implies that stimulating delayed rectifier potassium channels were involved in SO(2) derivative-caused hippocampal neuronal insults, and blocking these channels might be one of the possibly clinical treatment for SO(2)-caused neuronal dysfunction.

  3. Age-related infra-tentorial brain atrophy on CT scan

    International Nuclear Information System (INIS)

    Kitani, Mitsuhiro; Kobayashi, Shotai; Yamaguchi, Shuhei; Okada, Kazunori; Murata, Akihiro; Tsunematsu, Tokugoro

    1985-01-01

    We had reported that the brain atrophy progressed significantly with advancing age using the two dimensional CT measurement by digitizer which was connected with personal computer. Using this method, we studied the age-related infra-tentrial brain atrophy in 67 normal subjects (14-90 years), and compared that with age-related supra-tentrial brain atrophy. There was a significant correlation between age and all indices [cranio-ventricular index (CVI), ventricular area index (VAI) and brain atrophy index (BAI)] in supratentrial brain. These indices did not correlated to the age in infra-tentrial brain (brainstem and cerebellum). Significant change of the brain atrophy occured above 60 years old was observed by BAI and VAI in supra-tentrial brain. There was a significant correlation between supra-tentrial brain atrophy index (BAI) and that of infratentrial brain. These results indicate that age-related brain atrophy might progress more slowly in brainstem and cerebellum than in cerebrum. (author)

  4. Image-based diagnosis of alzheimer-type dementia. Measurements of hippocampal and ventricular areas in MR images

    International Nuclear Information System (INIS)

    Kodama, Naoki; Shimada, Tetsuo; Fukumoto, Ichiro

    2002-01-01

    We studied the possibility of objective diagnosis of Alzheimer-type dementia through radiological findings by evaluating cerebral and hippocampal atrophy in magnetic resonance images of patients with dementia. A statistically significant difference was seen in the hippocampus area index (HAI) and the ventricle area index (VAI) of healthy elderly individuals. Discriminant analysis with these two indexes demonstrated a sensitivity of 90.2% and a specificity of 81.8%, with an overall accuracy of 87.7%. Multiple discriminant analysis with VAI and HAI by stage of dementia showed an overall accuracy of 61.6% for discrimination of four stages. These results indicate that quantitative magnetic resonance imaging measurements can be used as an objective diagnostic technique for Alzheimer-type dementia. (author)

  5. Abnormal pain perception in patients with Multiple System Atrophy.

    Science.gov (United States)

    Ory-Magne, F; Pellaprat, J; Harroch, E; Galitzsky, M; Rousseau, V; Pavy-Le Traon, A; Rascol, O; Gerdelat, A; Brefel-Courbon, C

    2018-03-01

    Patients with Parkinson's disease or Multiple System Atrophy frequently experience painful sensations. The few studies investigating pain mechanisms in Multiple System Atrophy patients have reported contradictory results. In our study, we compared pain thresholds in Multiple System Atrophy and Parkinson's disease patients and healthy controls and evaluated the effect of l-DOPA on pain thresholds. We assessed subjective and objective pain thresholds (using a thermotest and RIII reflex), and pain tolerance in OFF and ON conditions, clinical pain, motor and psychological evaluation. Pain was reported in 78.6% of Multiple System Atrophy patients and in 37.5% of Parkinson's disease patients. In the OFF condition, subjective and objective pain thresholds were significantly lower in Multiple System Atrophy patients than in healthy controls (43.8 °C ± 1.3 vs 45.7 °C ± 0.8; p = 0.0005 and 7.4 mA ± 3.8 vs 13.7 mA ± 2.8; p = 0.002, respectively). They were also significantly reduced in Multiple System Atrophy compared to Parkinson's disease patients. No significant difference was found in pain tolerance for the 3 groups and in the effect of l-DOPA on pain thresholds in Multiple System Atrophy and Parkinson's disease patients. In the ON condition, pain tolerance tended to be reduced in Multiple System Atrophy versus Parkinson's disease patients (p = 0.05). Multiple System Atrophy patients had an increase in pain perception compared to Parkinson's disease patients and healthy controls. The l-DOPA effect was similar for pain thresholds in Multiple System Atrophy and Parkinson's disease patients, but tended to worsen pain tolerance in Multiple System Atrophy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Severe muscle atrophy due to spinal cord injury can be reversed in complete absence of peripheral nerves

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    Simona Boncompagni

    2012-12-01

    Full Text Available In the last years, a new efficient treatment has been developed to treat paralyzed skeletal muscle of patients affected by spinal cord injury (SCI. The capability of the functional electrical stimulation (FES to improve trophism and in some cases muscle function, are now well documented both in animals after experimental cord lesion, and in humans, generally after traumatic cord lesion. This new findings makes FES an important tool for the rehabilitation of SCI patients. FES stimulation has been proven to be an effective method used to retard muscle atrophy and improve recovery after reinnervation. Sophisticated FES devices have been developed for restoring function in the upper and lower extremities, the bladder and bowel, and the respiratory system of SCI patients. However, there are SCI cases, such as those affected by flaccid paralysis, in which the musculature is not treated with FES rehabilitation therapy. This is because conventional FES apparatuses are designed for direct stimulation of peripheral nerves that need small currents to be depolarized, and are not effective in patients that have lost their peripheral nerves, and, therefore, require higher currents for the direct depolarization of the muscle fibers. Lack of muscle treatment generates, as a secondary problem, a long series of alterations to tissues other than muscle, such as bones (osteoporosis, skin (pressure sores, decubital ulcers, etc., that are a direct consequence of inactivity and poor blood supply to the denervated areas. These complications represent an extremely serious problem for the general health of the injured individuals, who usually have a shorter than normal life span. In the hopes of changing this common belief, an innovative rehabilitation procedure, based on FES, has been developed with the aim of reversing long-lasting muscle atrophy in the muscles of the lower extremities of SCI patients affected by complete lesion of the conus cauda, i.e. that have no

  7. Ophthalmic manifestations of head injury.

    Science.gov (United States)

    Kowal, L

    1992-02-01

    Head injuries are frequently associated with ophthalmic problems. The commonest problems seen in this series of 161 patients with head injury were problems with poor accommodation (16% of patients; 58% of these persisted), convergence (14% of patients; 35% of these persisted), pseudomyopia (19%; 55% persisted) and optic atrophy (26% of the patients; 78% of these were mild and easily missed on routine testing, and 22% were severe). Motility disorders were common, especially cranial nerve palsies. Other less frequent motility disturbances included apparent inferior oblique palsy, comitant esotropia, and exotropia which was often of the convergence insufficiency type.

  8. Comparison of regional brain atrophy and cognitive impairment between pure akinesia with gait freezing and Richardson's syndrome

    Science.gov (United States)

    Hong, Jin Yong; Yun, Hyuk Jin; Sunwoo, Mun Kyung; Ham, Jee Hyun; Lee, Jong-Min; Sohn, Young H.; Lee, Phil Hyu

    2015-01-01

    Pure akinesia with gait freezing (PAGF) is considered a clinical phenotype of progressive supranuclear palsy. The brain atrophy and cognitive deficits in PAGF are expected to be less prominent than in classical Richardson's syndrome (RS), but this hypothesis has not been explored yet. We reviewed the medical records of 28 patients with probable RS, 19 with PAGF, and 29 healthy controls, and compared cortical thickness, subcortical gray matter volume, and neuropsychological performance among the three groups. Patients with PAGF had thinner cortices in frontal, inferior parietal, and temporal areas compared with controls; however, areas of cortical thinning in PAGF patients were less extensive than those in RS patients. In PAGF patients, hippocampal, and thalamic volumes were also smaller than controls, whereas subcortical gray matter volumes in PAGF and RS patients were comparable. In a comparison of neuropsychological tests, PAGF patients had better cognitive performance in executive function, visual memory, and visuospatial function than RS patients had. These results demonstrate that cognitive impairment, cortical thinning, and subcortical gray matter atrophy in PAGF patients resemble to those in RS patients, though the severity of cortical thinning and cognitive dysfunction is milder. Our results suggest that, PAGF and RS may share same pathology but that it appears to affect a smaller proportion of the cortex in PAGF. PMID:26483680

  9. Hemifacial atrophy treated with autologous fat transplantation

    Directory of Open Access Journals (Sweden)

    Gandhi Vijay

    2005-01-01

    Full Text Available A 23-year-old male developed right hemifacial atrophy following marphea profunda. Facial asymmetry due to residual atrophy was treated with autologous fat harvested from buttocks with marked cosmetic improvement.

  10. Pharmacological inhibition of myostatin protects against skeletal muscle atrophy and weakness after anterior cruciate ligament tear.

    Science.gov (United States)

    Wurtzel, Caroline Nw; Gumucio, Jonathan P; Grekin, Jeremy A; Khouri, Roger K; Russell, Alan J; Bedi, Asheesh; Mendias, Christopher L

    2017-11-01

    Anterior cruciate ligament (ACL) tears are among the most frequent knee injuries in sports medicine, with tear rates in the US up to 250,000 per year. Many patients who suffer from ACL tears have persistent atrophy and weakness even after considerable rehabilitation. Myostatin is a cytokine that directly induces muscle atrophy, and previous studies rodent models and patients have demonstrated an upregulation of myostatin after ACL tear. Using a preclinical rat model, our objective was to determine if the use of a bioneutralizing antibody against myostatin could prevent muscle atrophy and weakness after ACL tear. Rats underwent a surgically induced ACL tear and were treated with either a bioneutralizing antibody against myostatin (10B3, GlaxoSmithKline) or a sham antibody (E1-82.15, GlaxoSmithKline). Muscles were harvested at either 7 or 21 days after induction of a tear to measure changes in contractile function, fiber size, and genes involved in muscle atrophy and hypertrophy. These time points were selected to evaluate early and later changes in muscle structure and function. Compared to the sham antibody group, 7 days after ACL tear, myostatin inhibition reduced the expression of proteolytic genes and induced the expression of hypertrophy genes. These early changes in gene expression lead to a 22% increase in muscle fiber cross-sectional area and a 10% improvement in maximum isometric force production that were observed 21 days after ACL tear. Overall, myostatin inhibition lead to several favorable, although modest, changes in molecular biomarkers of muscle regeneration and reduced muscle atrophy and weakness following ACL tear. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2499-2505, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. Quantitative evaluation of tongue atrophy on midsagittal magnetic resonance images (MRIs)

    International Nuclear Information System (INIS)

    Ohnishi, Akio; Oishi, Tomonari; Murai, Yoshiyuki; Tsukamoto, Yoshiki; Ikeda, Masato

    1992-01-01

    This study was undertaken mainly to establish the quantitative parameter to evaluate the tongue atrophy on midsagittal MRIs and to show the clinical usefulness of such quantitative evaluation. Midsagittal MRIs of the tongue of consecutive 103 patients were analyzed. They were classified into 67 patients showing normal size (group without atrophy), 11 patients showing atrophy (group with atrophy) and 25 patients showing unsatifactory MRIs with artifacts based on the routine evaluation. The patients in the group without atrophy did not show any pathologic processes to produce tongue atrophy on clinical findings. The area and perimeter of tongue and oral cavity, and the ratio of tongue area to oral cavity area and the ratio of tongue perimeter to oral cavity perimeter on midsagittal MRIs were obtained in each patient of groups with and without atrophy by using quantitative image analysis system. In the group without atrophy, regression analysis of the data on age was made and the 95% confidence interval of the data for age was obtained. No evidence that the tongue becomes atrophic with aging was obtained in the group without atrophy. Patients in the group with atrophy were best separated from those in the group without atrophy statistically when the ratio of tongue area to oral cavity area was regressed on age. Among 11 patients in the group with atrophy, 6 patients were not regarded as having tongue atrophy on clinical neurological examinations. Therefore, the evaluation of midsagittal MRIs is clinically useful. (author)

  12. Features of amygdala in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: An MRI volumetric and histopathological study.

    Science.gov (United States)

    Nakayama, Yoko; Masuda, Hiroshi; Shirozu, Hiroshi; Ito, Yosuke; Higashijima, Takefumi; Kitaura, Hiroki; Fujii, Yukihiko; Kakita, Akiyoshi; Fukuda, Masafumi

    2017-09-01

    It is well-known that there is a correlation between the neuropathological grade of hippocampal sclerosis (HS) and neuroradiological atrophy of the hippocampus in mesial temporal lobe epilepsy (mTLE) patients. However, there is no strict definition or criterion regarding neuron loss and atrophy of the amygdala neighboring the hippocampus. We examined the relationship between HS and neuronal loss in the amygdala. Nineteen mTLE patients with neuropathological proof of HS were assigned to Group A, while seven mTLE patients without HS were assigned to Group B. We used FreeSurfer software to measure amygdala volume automatically based on pre-operation magnetic resonance images. Neurons observed using Klüver-Barrera (KB) staining in resected amygdala tissue were counted. and the extent of immunostaining with stress marker antibodies was semiquantitatively evaluated. There was no significant difference in amygdala volume between the two groups (Group A: 1.41±0.24; Group B: 1.41±0.29cm 3 ; p=0.98), nor in the neuron cellularity of resected amygdala specimens (Group A: 3.98±0.97; Group B: 3.67±0.67 10× -4 number of neurons/μm 2 ; p=0.40). However, the HSP70 level, representing acute stress against epilepsy, in Group A patients was significantly larger than that in Group B. There was no significant difference in the level of Bcl-2, which is known as a protein that inhibits cell death, between the two groups. Neuronal loss and volume loss in the amygdala may not necessarily follow hippocampal sclerosis. From the analysis of stress proteins, epileptic attacks are as likely to damage the amygdala as the hippocampus but do not lead to neuronal death in the amygdala. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Temporal lobe sclerosis associated with hippocampal sclerosis in temporal lobe epilepsy: neuropathological features.

    Science.gov (United States)

    Thom, Maria; Eriksson, Sofia; Martinian, Lillian; Caboclo, Luis O; McEvoy, Andrew W; Duncan, John S; Sisodiya, Sanjay M

    2009-08-01

    Widespread changes involving neocortical and mesial temporal lobe structures can be present in patients with temporal lobe epilepsy and hippocampal sclerosis. The incidence, pathology, and clinical significance of neocortical temporal lobe sclerosis (TLS) are not well characterized. We identified TLS in 30 of 272 surgically treated cases of hippocampal sclerosis. Temporal lobe sclerosis was defined by variable reduction of neurons from cortical layers II/III and laminar gliosis; it was typically accompanied by additional architectural abnormalities of layer II, that is, abnormal neuronal orientation and aggregation. Quantitative analysis including tessellation methods for the distribution of layer II neurons supported these observations. In 40% of cases, there was a gradient of TLS with more severe involvement toward the temporal pole, possibly signifying involvement of hippocampal projection pathways. There was a history of a febrile seizure as an initial precipitating injury in 73% of patients with TLS compared with 36% without TLS; no other clinical differences between TLS and non-TLS cases were identified. Temporal lobe sclerosis was not evident preoperatively by neuroimaging. No obvious effect of TLS on seizure outcome was noted after temporal lobe resection; 73% became seizure-free at 2-year follow-up. In conclusion, approximately 11% of surgically treated hippocampal sclerosis is accompanied by TLS. Temporal lobe sclerosis is likely an acquired process with accompanying reorganizational dysplasia and an extension of mesial temporal sclerosis rather than a separate pathological entity.

  14. The value of structural MRI measurements of cerebral atrophy in predicting the rate of cognitive decline in the non-demented elderly: a GEE analysis based on data from the Vienna transdanube aging study

    International Nuclear Information System (INIS)

    Roesel, M.

    2011-01-01

    The main objective of this study was the assessment of various structural measurements of cerebral atrophy at baseline and the evaluation of their potential value in predicting future cognitive decline in a longitudinal study design. Data were drawn from the Vienna Transdanube Aging (VITA) study. Magnetic resonance images of 532 subjects aged 75-76 years at baseline were analyzed to assess 8 different cerebral atrophy markers. A population averaged model with the corresponding analytical technique of generalized estimating equations (GEE) were applied to the birth-cohort to assess associations between the MRI-based atrophy markers and 6 cognitive test scores at baseline and two follow-up investigations. Cognitive tests were comprised of the Mini Mental State Examination (MMSE), Boston Naming Test (BNT), Fuld Object Memory Evaluation (FOME), Verbal Fluency (VF) and the Trail Making Tests A and B (TMTA, TMTB). Vascular risk factors and several other covariates that were available in the VITA database were included as additional predictors in the longitudinal data analysis. Severity of right hippocampal head atrophy predicted the rate of cognitive decline in all 6 test scores. (MMSE: β =-0.507; p = 0.002, BNT: β = -1.090; p = 0.004, FOME: β = -0.291; p = 0.003, VF: β = 0.718; p = 0.025, TMTA: Exp(β) = 0.123; p [de

  15. Evaluation of both perfusion and atrophy in multiple system atrophy of the cerebellar type using brain SPECT alone

    International Nuclear Information System (INIS)

    Matsuda, Hiroshi; Imabayashi, Etsuko; Kuji, Ichiei; Seto, Akira; Ito, Kimiteru; Kikuta, Daisuke; Yamada, Minoru; Shimano, Yasumasa; Sato, Noriko

    2010-01-01

    Partial volume effects in atrophied areas should be taken into account when interpreting brain perfusion single photon emission computed tomography (SPECT) images of neurodegenerative diseases. To evaluate both perfusion and atrophy using brain SPECT alone, we developed a new technique applying tensor-based morphometry (TBM) to SPECT. After linear spatial normalization of brain perfusion SPECT using 99m Tc-ethyl cysteinate dimer ( 99m Tc-ECD) to a Talairach space, high-dimension-warping was done using an original 99m Tc-ECD template. Contraction map images calculated from Jacobian determinants and spatially normalized SPECT images using this high-dimension-warping were compared using statistical parametric mapping (SPM2) between two groups of 16 multiple system atrophy of the cerebellar type (MSA-C) patients and 73 age-matched normal controls. This comparison was also performed in conventionally warped SPECT images. SPM2 demonstrated statistically significant contraction indicating local atrophy and decreased perfusion in the whole cerebellum and pons of MSA-C patients as compared to normal controls. Higher significance for decreased perfusion in these areas was obtained in high-dimension-warping than in conventional warping, possibly due to sufficient spatial normalization to a 99m Tc-ECD template in high-dimensional warping of severely atrophied cerebellum and pons. In the present high-dimension-warping, modification of tracer activity remained within 3% of the original tracer distribution. The present new technique applying TBM to brain SPECT provides information on both perfusion and atrophy at the same time thereby enhancing the role of brain perfusion SPECT

  16. Evaluation of both perfusion and atrophy in multiple system atrophy of the cerebellar type using brain SPECT alone

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    Matsuda Hiroshi

    2010-08-01

    Full Text Available Abstract Background Partial volume effects in atrophied areas should be taken into account when interpreting brain perfusion single photon emission computed tomography (SPECT images of neurodegenerative diseases. To evaluate both perfusion and atrophy using brain SPECT alone, we developed a new technique applying tensor-based morphometry (TBM to SPECT. Methods After linear spatial normalization of brain perfusion SPECT using 99mTc-ethyl cysteinate dimer (99mTc-ECD to a Talairach space, high-dimension-warping was done using an original 99mTc-ECD template. Contraction map images calculated from Jacobian determinants and spatially normalized SPECT images using this high-dimension-warping were compared using statistical parametric mapping (SPM2 between two groups of 16 multiple system atrophy of the cerebellar type (MSA-C patients and 73 age-matched normal controls. This comparison was also performed in conventionally warped SPECT images. Results SPM2 demonstrated statistically significant contraction indicating local atrophy and decreased perfusion in the whole cerebellum and pons of MSA-C patients as compared to normal controls. Higher significance for decreased perfusion in these areas was obtained in high-dimension-warping than in conventional warping, possibly due to sufficient spatial normalization to a 99mTc-ECD template in high-dimensional warping of severely atrophied cerebellum and pons. In the present high-dimension-warping, modification of tracer activity remained within 3% of the original tracer distribution. Conclusions The present new technique applying TBM to brain SPECT provides information on both perfusion and atrophy at the same time thereby enhancing the role of brain perfusion SPECT

  17. Comparison of Hippocampal Volume in Dementia Subtypes

    International Nuclear Information System (INIS)

    Vijayakumar, Avinash; Vijayakumar, Abhishek

    2012-01-01

    Aims. To examine the relationship between different types of dementia and hippocampal volume. Methods. Hippocampal volume was measured using FL3D sequence magnetic resonance imaging in 26 Alzheimer's, vascular dementia, mixed dementia, and normal pressure hydrocephalus patients and 15 healthy controls and also hippocampal ratio, analyzed. Minimental scale was used to stratify patients on cognitive function impairments. Results. Hippocampal volume and ratio was reduced by 25% in Alzheimer's disease, 21% in mixed dementia, 11% in vascular dementia and 5% in normal pressure hydrocephalus in comparison to control. Also an asymmetrical decrease in volume of left hippocampus was noted. The severity of dementia increased in accordance to decreasing hippocampal volume. Conclusion. Measurement in hippocampal volume may facilitate in differentiating different types of dementia and in disease progression. There was a correlation between hippocampal volume and severity of cognitive impairment

  18. Frontal parenchymal atrophy measures in multiple sclerosis.

    Science.gov (United States)

    Locatelli, Laura; Zivadinov, Robert; Grop, Attilio; Zorzon, Marino

    2004-10-01

    The aim of this study was to establish whether, in a cross-sectional study, the normalized measures of whole and regional brain atrophy correlate better with tests assessing the cognitive function than the absolute brain atrophy measures. The neuropsychological performances and disability have been assessed in 39 patients with relapsing-remitting multiple sclerosis (MS). T1- and T2-lesion load (LL) of total brain and frontal lobes (FLs) were measured using a reproducible semiautomated technique. The whole brain volume and the regional brain parenchymal volume (RBPV) of FLs were obtained using a computerized interactive program, which incorporates semiautomated and automated segmentation processes. Normalized measures of brain atrophy, i.e., brain parenchymal fraction (BPF) and regional brain parenchymal fraction (RBPF) of FLs, were calculated. The scan-rescan, inter- and intrarater coefficient of variation (COV) and intraclass correlation coefficient (ICC) have been estimated. The RBPF of FLs showed an acceptable level of reproducibility which ranged from 1.7% for intrarater variability to 3.2% for scan-rescan variability. The mean ICC was 0.88 (CI 0.82-0.93). The RBPF of FLs demonstrated stronger magnitudes of correlation with neuropsychological functioning, disability and quantitative MRI lesion measures than RBPV. These differences were statistically significant: PColor Word Interference test, Pcognitive functions, whereas BPAV did not. The correlation analysis results were supported by the results of multiple regression analysis which showed that only the normalized brain atrophy measures were associated with tests exploring the cognitive functions. These data suggest that RBPF is a reproducible and sensitive method for measuring frontal parenchymal atrophy. The normalized measures of whole and regional brain parenchymal atrophy should be preferred to absolute measures in future studies that correlate neuropsychological performances and brain atrophy measures

  19. MRI study of degenerative process in multiple system atrophy

    International Nuclear Information System (INIS)

    Yagishita, Toshiyuki; Kojima, Shigeyuki; Hirayama, Keizo

    1995-01-01

    The characteristic morphological changes of the brainstem and cerebellar regions of multiple system atrophy (MSA) were studied by MRI in varing subtypes, that is olivoponto cerebellar atrophy (OPCA: 23 cases), striatonigral degeneration (SND: 7 cases) and Shy-Drager's syndrome (SDS: 9 cases). OPCA was characterized by atrophy of the entire regions of the brainstem and the cerebellum. SND and SDS tended to show atrophy similar in type but lessin extent to OPCA. The common lesions in MSA were atrophy of the pontine base and cerebellum, and dilation of the fourth ventricle. Atrophy of the pontine base was more dominant in the inferior part than in the superior part, and cerebellar atrophy was more dominant in the superior part than in the inferior part, indicating that degeneration of the pontocerebellar pathway proceeds principally along fibers connecting the inferior part of the pons and the superior part of the cerebellum. Dilation of the fourth ventricle indicated atrophy of the middle cerebellar peduncle. In almost all the cases of OPCA and about a half the cases of SND and SDS, the pontine base and the middle cerebellar peduncle appeared as high signal intensity on T 2 weighted image and as low intensity on T 1 , suggesting degeneration and demyelination. In a few cases of OPCA, the dorsolateral part of the putamen were demonstrated as low signal intensity on T 2 weighted image. (author)

  20. Traumatic Brain Injury Severity, Neuropathophysiology, and Clinical Outcome: Insights from Multimodal Neuroimaging

    Directory of Open Access Journals (Sweden)

    Andrei Irimia

    2017-10-01

    Full Text Available BackgroundThe relationship between the acute clinical presentation of patients with traumatic brain injury (TBI, long-term changes in brain structure prompted by injury and chronic functional outcome is insufficiently understood. In this preliminary study, we investigate how acute Glasgow coma score (GCS and epileptic seizure occurrence after TBIs are statistically related to functional outcome (as quantified using the Glasgow Outcome Score and to the extent of cortical thinning observed 6 months after the traumatic event.MethodsUsing multivariate linear regression, the extent to which the acute GCS and epileptic seizure occurrence (predictor variables correlate with structural brain changes (relative cortical atrophy was examined in a group of 33 TBI patients. The statistical significance of the correlation between relative cortical atrophy and the Glasgow Outcome Score was also investigated.ResultsA statistically significant correlative relationship between cortical thinning and the predictor variables (acute GCS and seizure occurrence was identified in the study sample. Regions where the statistical model was found to have highest statistical reliability in predicting both gray matter atrophy and neurological outcome include the frontopolar, middle frontal, postcentral, paracentral, middle temporal, angular, and lingual gyri. In addition, relative atrophy and GOS were also found to be significantly correlated over large portions of the cortex.ConclusionThis study contributes to our understanding of the relationship between clinical descriptors of acute TBI, the extent of injury-related chronic brain changes and neurological outcome. This is partly because the brain areas where cortical thinning was found to be correlated with GCS and with seizure occurrence are implicated in executive control, sensory function, motor acuity, memory, and language, all of which may be affected by TBI. Thus, our quantification suggests the existence of a

  1. Comparison of regional brain atrophy and cognitive impairment between pure akinesia with gait freezing and Richardson’s syndrome

    Directory of Open Access Journals (Sweden)

    Jin Yong eHong

    2015-09-01

    Full Text Available Pure akinesia with gait freezing (PAGF is considered a clinical phenotype of progressive supranuclear palsy. The brain atrophy and cognitive deficits in PAGF are expected to be less prominent than in classical Richardson’s syndrome (RS, but this hypothesis has not been explored yet. We reviewed the medical records of 28 patients with probable RS, 19 with PAGF, and 29 healthy controls, and compared cortical thickness, subcortical grey matter volume, and neuropsychological performance among the three groups. Patients with PAGF had thinner cortices in frontal, inferior parietal, and temporal areas compared with controls; however, areas of cortical thinning in PAGF patients were less extensive than those in RS patients. In PAGF patients, hippocampal and thalamic volumes were also smaller than controls, whereas subcortical grey matter volumes in PAGF and RS patients were comparable. In a comparison of neuropsychological tests, PAGF patients had better cognitive performance in executive function, visual memory, and visuospatial function than RS patients had. These results demonstrate that cognitive impairment, cortical thinning, and subcortical grey matter atrophy in PAGF patients resemble to those in RS patients, though the severity of cortical thinning and cognitive dysfunction is milder. Our results suggest that PAGF and RS may share same pathology but that it appears to affect a smaller proportion of the cortex in PAGF.

  2. Differential regulation of the Rac1 GTPase-activating protein (GAP) BCR during oxygen/glucose deprivation in hippocampal and cortical neurons.

    Science.gov (United States)

    Smith, Katharine R; Rajgor, Dipen; Hanley, Jonathan G

    2017-12-08

    Brain ischemia causes oxygen and glucose deprivation (OGD) in neurons, triggering a cascade of events leading to synaptic accumulation of glutamate. Excessive activation of glutamate receptors causes excitotoxicity and delayed cell death in vulnerable neurons. Following global cerebral ischemia, hippocampal CA1 pyramidal neurons are more vulnerable to injury than their cortical counterparts, but the mechanisms that underlie this difference are unclear. Signaling via Rho-family small GTPases, their upstream guanine nucleotide exchange factors, and GTPase-activating proteins (GAPs) is differentially dysregulated in response to OGD/ischemia in hippocampal and cortical neurons. Increased Rac1 activity caused by OGD/ischemia contributes to neuronal death in hippocampal neurons via diverse effects on NADPH oxidase activity and dendritic spine morphology. The Rac1 guanine nucleotide exchange factor Tiam1 mediates an OGD-induced increase in Rac1 activity in hippocampal neurons; however, the identity of an antagonistic GAP remains elusive. Here we show that the Rac1 GAP breakpoint cluster region (BCR) associates with NMDA receptors (NMDARs) along with Tiam1 and that this protein complex is more abundant in hippocampal compared with cortical neurons. Although total BCR is similar in the two neuronal types, BCR is more active in hippocampal compared with cortical neurons. OGD causes an NMDAR- and Ca 2+ -permeable AMPAR-dependent deactivation of BCR in hippocampal but not cortical neurons. BCR knockdown occludes OGD-induced Rac1 activation in hippocampal neurons. Furthermore, disrupting the Tiam1-NMDAR interaction with a fragment of Tiam1 blocks OGD-induced Tiam1 activation but has no effect on the deactivation of BCR. This work identifies BCR as a critical player in Rac1 regulation during OGD in hippocampal neurons. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. MRI study of degenerative process in multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Yagishita, Toshiyuki; Kojima, Shigeyuki; Hirayama, Keizo [Chiba Univ. (Japan). School of Medicine

    1995-02-01

    The characteristic morphological changes of the brainstem and cerebellar regions of multiple system atrophy (MSA) were studied by MRI in varing subtypes, that is olivoponto cerebellar atrophy (OPCA: 23 cases), striatonigral degeneration (SND: 7 cases) and Shy-Drager`s syndrome (SDS: 9 cases). OPCA was characterized by atrophy of the entire regions of the brainstem and the cerebellum. SND and SDS tended to show atrophy similar in type but lessin extent to OPCA. The common lesions in MSA were atrophy of the pontine base and cerebellum, and dilation of the fourth ventricle. Atrophy of the pontine base was more dominant in the inferior part than in the superior part, and cerebellar atrophy was more dominant in the superior part than in the inferior part, indicating that degeneration of the pontocerebellar pathway proceeds principally along fibers connecting the inferior part of the pons and the superior part of the cerebellum. Dilation of the fourth ventricle indicated atrophy of the middle cerebellar peduncle. In almost all the cases of OPCA and about a half the cases of SND and SDS, the pontine base and the middle cerebellar peduncle appeared as high signal intensity on T{sub 2} weighted image and as low intensity on T{sub 1}, suggesting degeneration and demyelination. In a few cases of OPCA, the dorsolateral part of the putamen were demonstrated as low signal intensity on T{sub 2} weighted image. (author).

  4. Longitudinal volumetric changes following traumatic brain injury: a tensor-based morphometry study.

    Science.gov (United States)

    Farbota, Kimberly D M; Sodhi, Aparna; Bendlin, Barbara B; McLaren, Donald G; Xu, Guofan; Rowley, Howard A; Johnson, Sterling C

    2012-11-01

    After traumatic injury, the brain undergoes a prolonged period of degenerative change that is paradoxically accompanied by cognitive recovery. The spatiotemporal pattern of atrophy and the specific relationships of atrophy to cognitive changes are ill understood. The present study used tensor-based morphometry and neuropsychological testing to examine brain volume loss in 17 traumatic brain injury (TBI) patients and 13 controls over a 4-year period. Patients were scanned at 2 months, 1 year, and 4 years post-injury. High-dimensional warping procedures were used to create change maps of each subject's brain for each of the two intervals. TBI patients experienced volume loss in both cortical areas and white matter regions during the first interval. We also observed continuing volume loss in extensive regions of white matter during the second interval. Neuropsychological correlations indicated that cognitive tasks were associated with subsequent volume loss in task-relevant regions. The extensive volume loss in brain white matter observed well beyond the first year post-injury suggests that the injured brain remains malleable for an extended period, and the neuropsychological relationships suggest that this volume loss may be associated with subtle cognitive improvements.

  5. Novel genetic loci associated with hippocampal volume.

    Science.gov (United States)

    Hibar, Derrek P; Adams, Hieab H H; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L; Hofer, Edith; Renteria, Miguel E; Bis, Joshua C; Arias-Vasquez, Alejandro; Ikram, M Kamran; Desrivières, Sylvane; Vernooij, Meike W; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H; Beiser, Alexa; Bernard, Manon; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Gutman, Boris A; Hass, Johanna; Haukvik, Unn K; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre F; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; McKay, David R; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C; Nyquist, Paul; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Saremi, Arvin; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Lee, Sven J; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Craen, Anton J M; De Geus, Eco J C; De Jager, Philip L; De Zubicaray, Greig I; Deary, Ian J; Debette, Stéphanie; DeCarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J A; Van Haren, Neeltje E M; van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Vellas, Bruno; Veltman, Dick J; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, Ronald H; Zonderman, Alan B; Martin, Nicholas G; Van Duijn, Cornelia M; Wright, Margaret J; Longstreth, W T; Schumann, Gunter; Grabe, Hans J; Franke, Barbara; Launer, Lenore J; Medland, Sarah E; Seshadri, Sudha; Thompson, Paul M; Ikram, M Arfan

    2017-01-18

    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r g =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

  6. Novel in vitro platform to investigate myotube atrophy

    OpenAIRE

    Oelkrug, Christopher; Horn, Katharina; Makert, Gustavo R.; Schubert, Andreas

    2015-01-01

    The electrical current exclusion (ECE) principle provides an alternative to common methods of cell diameter measurement and especially in atrophy and cancer associated cachexia research. C2C12 myoblasts were differentiated into myotubes and treated with 100 μM dexamethasone to induce atrophy in vitro. Subsequently, they were incubated for 24 h with media containing different concentrations of curcumin and/or branched-chain amino acids (BCAAs) in order to counteract atrophy. After treatment wi...

  7. Bilateral optical nerve atrophy secondary to lateral occipital lobe infarction.

    Science.gov (United States)

    Mao, Junfeng; Wei, Shihui

    2013-06-01

    To report a phenomenon of optical nerve atrophy secondary to lateral occipital lobe infarction. Two successive patients with unilateral occipital lobe infarction who experienced bilateral optical nerve atrophy during the follow-up underwent cranial imaging, fundus photography, and campimetry. Each patient was diagnosed with occipital lobe infarction by cranial MRI. During the follow-up, a bilateral optic atrophy was revealed, and campimetry showed a right homonymous hemianopia of both eyes with concomitant macular division. Bilateral optic atrophy was related to occipital lobe infarction, and a possible explanation for the atrophy was transneuronal degeneration caused by occipital lobe infarction.

  8. Novel genetic loci associated with hippocampal volume

    OpenAIRE

    Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivieres, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf

    2017-01-01

    International audience; The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal ...

  9. Four cases with localized brain-stem lesion on CT scan following closed head injury

    International Nuclear Information System (INIS)

    Saeki, Naokatsu; Odaki, Masaru; Oka, Nobuo; Takase, Manabu; Ono, Junichi.

    1981-01-01

    Cases of primary brain-stem injury following closed head injury, verified by a CT scan, have been increasingly reported. However, most of them have other intracranial lesions in addition to the brain stem, resulting in a poor outcome. The CT scan of 200 cases with severe head injury-Araki's classification of types 3 and 4 - were analysed. Four cases out of them had localized brain-stem lesion without any other significant intracranial injury on a CT scan at the acute stage and had a better outcome than had previously been reported. In this analysis, these 4 cases were studied, and the CT findings, prognosis, and pathogenesis of the localized brain-stem injury were discussed. Follow-up CT of three cases, and taken one month or more later, showed diffuse cortical atrophy. This may indicate the presence of diffuse cerebral injury which could not be seen on CT scans at the acute stage. This atrophic change may also be related with the mechanism of posttraumatic conscious impairment and posttraumatic neurological deficits, such as mental symptoms and impairment of the higher cortical function. Shearing injury is a probable pathogenesis for this diffuse cortical injury. On the other hand, one case did not have any cortical atrophy on a follow-up CT scan. Therefore, this is a case with a localized primary brain-stem injury. Coup injury against the brain stem by a tentorial margin in a case with a small tentorial opening is a possible mechanism producing the localized brain-stem injury. (J.P.N.)

  10. Characterization of disuse skeletal muscle atrophy and the efficacy of a novel muscle atrophy countermeasure during spaceflight and simulated microgravity

    Science.gov (United States)

    Hanson, Andrea Marie

    Humans are an integral part of the engineered systems that will enable return to the Moon and eventually travel to Mars. Major advancements in countermeasure development addressing deleterious effects of microgravity and reduced gravity on the musculoskeletal system need to be made to ensure mission safety and success. The primary objectives of this dissertation are to advance the knowledge and understanding of skeletal muscle atrophy, and support development of novel countermeasures for disuse atrophy to enable healthy long-duration human spaceflight. Models simulating microgravity and actual spaceflight were used to examine the musculoskeletal adaptations during periods of unloading. Myostatin inhibition, a novel anti-atrophy drug therapy, and exercise were examined as a means of preventing and recovering from disuse atrophy. A combination of assays was used to quantify adaptation responses to unloading and examine efficacy of the countermeasures. Body and muscle masses were collected to analyze systemic changes due to treatments. Hindlimb strength and individual muscle forces were measured to demonstrate functional adaptations to treatments. Muscle fiber morphology and myosin heavy chain (MHC) expression was examined to identify adaptations at the cellular level. Protein synthesis signals insulin-like growth factor-1 (IGF-1), Akt, and p70s6 kinase; and the degradation signals Atrogin-1 and MuRF-1 were examined to identify adaptations at the molecular level that ultimately lead to muscle hypertrophy and atrophy. A time course study provided a thorough characterization of the adaptation of skeletal muscle during unloading in C57BL/6 mice, and baseline data for comparison to and evaluation of subsequent studies. Time points defining the on-set and endpoints of disuse muscle atrophy were identified to enable characterization of rapid vs. long-term responses of skeletal muscle to hindlimb suspension. Unloading-induced atrophy primarily resulted from increased protein

  11. An MRI study on the relations between muscle atrophy, shoulder function and glenohumeral deformity in shoulders of children with obstetric brachial plexus injury

    Directory of Open Access Journals (Sweden)

    van Doorn-Loogman Mirjam H

    2009-05-01

    Full Text Available Abstract Background A substantial number of children with an obstetric brachial plexus lesion (OBPL will develop internal rotation adduction contractures of the shoulder, posterior humeral head subluxations and glenohumeral deformities. Their active shoulder function is generally limited and a recent study showed that their shoulder muscles were atrophic. This study focuses on the role of shoulder muscles in glenohumeral deformation and function. Methods This is a prospective study on 24 children with unilateral OBPL, who had internal rotation contractures of the shoulder (mean age 3.3 years, range 14.7 months to 7.3 years. Using MR imaging from both shoulders the following parameters were assessed: glenoid form, glenoscapular angle, subluxation of the humeral head, thickness and segmental volume of the subscapularis, infraspinatus and deltoid muscles. Shoulder function was assessed measuring passive external rotation of the shoulder and using the Mallet score for active function. Statistical tests used are t-tests, Spearman's rho, Pearsons r and logistic regression. Results The affected shoulders showed significantly reduced muscle sizes, increased glenoid retroversion and posterior subluxation. Mean muscle size compared to the normal side was: subscapularis 51%, infraspinatus 61% and deltoid 76%. Glenoid form was related to infraspinatus muscle atrophy. Subluxation was related to both infraspinatus and subscapularis atrophy. There was no relation between atrophy of muscles and passive external rotation. Muscle atrophy was not related to the Mallet score or its dimensions. Conclusion Muscle atrophy was more severe in the subscapularis muscle than in infraspinatus and deltoid. As the muscle ratios are not related to passive external rotation nor to active function of the shoulder, there must be other muscle properties influencing shoulder function.

  12. Lumbosacral Plexus Injury and Brachial Plexus Injury Following Prolonged Compression

    Directory of Open Access Journals (Sweden)

    Chung-Lan Kao

    2006-11-01

    Full Text Available We report the case of a 36-year-old woman who developed right upper and lower limb paralysis with sensory deficit after sedative drug overdose with prolonged immobilization. Due to the initial motor and sensory deficit pattern, brachial plexus injury or C8/T1 radiculopathy was suspected. Subsequent nerve conduction study/electromyography proved the lesion level to be brachial plexus. Painful swelling of the right buttock was suggestive of gluteal compartment syndrome. Elevation of serum creatine phosphokinase and urinary occult blood indicated rhabdomyolysis. The patient received medical treatment and rehabilitation; 2 years after the injury, her right upper and lower limb function had recovered nearly completely. As it is easy to develop complications such as muscle atrophy and joint contracture during the paralytic period of brachial plexopathy and lumbosacral plexopathy, early intervention with rehabilitation is necessary to ensure that the future limb function of the patient can be recovered. Our patient had suspected gluteal compartment syndrome that developed after prolonged compression, with the complication of concomitant lumbosacral plexus injury and brachial plexus injury, which is rarely reported in the literature. A satisfactory outcome was achieved with nonsurgical management.

  13. Intention tremor after head injury

    International Nuclear Information System (INIS)

    Iwadate, Yasuo; Saeki, Naokatsu; Namba, Hiroki; Odaki, Masaru; Oka, Nobuo.

    1989-01-01

    Eight cases of intention tremor as a late complication of head injury were investigated. The patients ranged in age from 3 to 24 years. All received severe head injuries and lapsed into coma immediately afterward (Glasgow Coma Scale scores ≤8). Six patients exhibited decerebration or decortication. Hemiparesis was present in six cases and oculomotor nerve palsy in four. In the chronic stage, all patients displayed some degree of impairment of higher cortical function and five had dysarthria and/or ataxia. Initial computed tomography (CT) scans within 3 hours after the injury were obtained in five cases, of which four showed a hemorrhagic lesion in the midbrain or its surroundings. Other CT findings were diffuse cerebral swelling (four cases), intraventricular hemorrhage (three), and multiple hemorrhagic lesions (two). In the chronic stage, generalized cortical atrophy or ventricular enlargement was noted in five cases. These clinical features and CT findings indicate diffuse brain damage as well as midbrain damage and may reflect shearing injury. (author)

  14. Spinal cord lesion by minor trauma as an early sign of Multiple System Atrophy

    Directory of Open Access Journals (Sweden)

    Marisa Tavares Brum

    2016-03-01

    Full Text Available Multiple System Atrophy (MSA is characterized clinically by parkinsonism, cerebellar, autonomic and corticospinal features of variable severity. When the presentation is only parkinsonism, the disease might be difficult to differentiate from Parkinson´s Disease (PD. We present a case of an 80-year-old man with previous diagnosis of PD. One year after diagnosis he had a whiplash cervical trauma due to a tricycle accident caused by a hole in the road. This low-energy trauma caused an unstable C4-C5 cervical fracture with spinal cord injury which required surgical decompression and stabilization. Neurological examination showed marked postural instability, no rest and postural tremor, finger tapping slowed on the right, spastic tetraparesis (ASIA D—predominantly on the left side—, brisk deep tendon reflexes in the upper and lower extremities and bilateral extensor plantar response. He also presented with vertical gaze restriction, mild hypometria in horizontal saccades, moderate dysphagia and dysphonia. As atypical parkinsonism was suspected he underwent an MRI which revealed conjunction of findings suggestive of parkinsonian-type multiple system atrophy (MSA. In our case we hypothesise that the loss of postural reflexes, as an early manifestation of MSA, did not allow the patient to have an effective reaction response to a low-energy trauma, resulting in a more severe injury. With this case report we speculate that the severe spinal lesions caused by minor accidents can be an early sign of postural instability, which may lead to clinical suspicion of neurodegenerative disorder manifested by postural reflexes impairment.

  15. Stress, depression and hippocampal damage

    Indian Academy of Sciences (India)

    Amongst the prime targets of stress in the brain is the hippocampus, which has high receptor ... effects on different hippocampal subfields (McEwen 1999). ... disorders, and decreases in hippocampal volume have been observed in patients of ...

  16. Brain atrophy and dementia from the aspect of CT

    International Nuclear Information System (INIS)

    Ohkuni, Michiko

    1979-01-01

    Two major causes of dementia in the elderly are reported to be the degeneration of brain and cerebrovascular diseases. Recently, CT findings of cerebrovascular diseases and brain atrophy have been noticed, because they rather clearly show these changes. The authors examined the view of atrophy frequently observed on the dementia in the elderly. The results obtained are as follows: 1) In accordance with the increase of age the appearance of the view of atrophy increased in frequency and that of extreme brain atrophy also increased. 2) As the age increased, the average value of the width of the 3rd ventricle tended to increase. 3) In the cases accompanied with the view of cerebrovascular diseases remarkable ventricular dilatation was frequently observed, and in the very old dilatations of cerebral sulci, central fissure and Sylvian fissure were observed of all cases. 4) Of the group of severe dementia the view of extreme brain atrophy was observed in the major. However, there was no significant difference on the lesion of atrophy between the cases. The results mentioned above include some exceptional points respectively, so further investigation will be necessary from the qualitative and quantitative points of view. (author)

  17. Melatonin successfully rescues hippocampal bioenergetics and improves cognitive function following drug intoxication by promoting Nrf2-ARE signaling activity.

    Science.gov (United States)

    Chen, Li-You; Renn, Ting-Yi; Liao, Wen-Chieh; Mai, Fu-Der; Ho, Ying-Jui; Hsiao, George; Lee, Ai-Wei; Chang, Hung-Ming

    2017-09-01

    Prolonged exposure to gamma-hydroxybutyric acid (GHB) would cause drug intoxication in which impaired cognitive function results from enhanced hippocampal oxidative stress may serve as a major symptom in this deficiency. Considering melatonin possesses significant anti-oxidative efficacy, this study aimed to determine whether melatonin would successfully promote the nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) signaling, depress oxidative stress, and rescue hippocampal bioenergetics and cognitive function following drug intoxication injury. Adolescent rats subjected to 10 days of GHB were received melatonin at doses of either 10 or 100 mg/kg. Time-of-flight secondary ion mass spectrometry, biochemical assay, quantitative histochemistry, [ 14 C]-2-deoxyglucose analysis, together with Morris water maze were employed to detect the molecular signaling, oxidative status, bioenergetic level, as well as the cognitive performances, respectively. Results indicated that in GHB-intoxicated rats, enhanced oxidative stress, increased cholesterol level, and decreased anti-oxidative enzymes activities were detected in hippocampal regions. Intense oxidative stress paralleled well with reduced bioenergetics and poor performance in behavioral testing. However, in rats treated with melatonin following GHB intoxication, all above parameters and cognitive function were gradually returned to nearly normal levels. Melatonin also remarkably promoted the translocation of Nrf2 from cytoplasm to nucleus in a dose-dependent manner, thereby increased the Nrf2-ARE signaling-related downstream anti-oxidative enzymes activities. As melatonin effectively rescues hippocampal bioenergetics through depressing the oxidative stress by promoting Nrf2-ARE molecular machinery, this study thus highlights for the first time that clinical use of melatonin may serve as a therapeutic strategy to improve the cognitive function in unsuspecting victims suffered from

  18. Diagnosis and treatment of the hemiplegic patient with brachial plexus injury.

    Science.gov (United States)

    Meredith, J; Taft, G; Kaplan, P

    1981-10-01

    Brachial plexus injury was observed as a complication in 5 of 12 hemiplegic patients admitted over a 5-week period to an inpatient unit of the Rehabilitation Institute of Chicago. These patients exhibited unusual patterns of muscle atrophy and return of function in the impaired upper extremity. Occupational therapists may play an important part in the diagnosis and treatment of this complication of hemiplegia by promptly recognizing its subtle clinical signs and instituting appropriate therapy. Electromyography may be recommended to confirm this diagnosis. The treatment of choice is to maintain correct positioning of the limb both day and night, to use facilitation techniques for specific muscles in order to prevent atrophy, and to maintain passive range of motion as much as possible. Prevention of brachial plexus injury depends largely on the education of patient, family, and staff as to the potential hazards to a frail extremity that has no protective responses.

  19. Peripapillary retinal thermal coagulation following electrical injury

    Directory of Open Access Journals (Sweden)

    Manjari Tandon

    2013-01-01

    Full Text Available In this study, we have presented the case report of a 20 year old boy who suffered an electric injury shock, following which he showed peripapillary retinal opacification and increased retinal thickening that subsequently progressed to retinal atrophy. The fluorescein angiogram revealed normal retinal circulation, thus indicating thermal damage to retina without any compromise to retinal circulation.

  20. Neuroprotective effects of ginsenoside Rg1 against oxygen–glucose deprivation in cultured hippocampal neurons

    OpenAIRE

    He, Qing; Sun, Jianguo; Wang, Qin; Wang, Wei; He, Bin

    2014-01-01

    Background: Ginsenoside Rg1 (Rg1) is believed to be one of the main active principles in ginseng, a traditional Chinese medicine extensively used to enhance stamina and deal with fatigue as well as physical stress. It has been reported that Rg1 performs multiple biological activities, including neuroprotective activity. In this study, we investigated the efficacy of ginsenoside Rg1 on ischemia–reperfusion injury in cultured hippocampal cells and also probed its possible mechanisms. Methods...

  1. Experimental model considerations for the study of protein-energy malnutrition co-existing with ischemic brain injury.

    Science.gov (United States)

    Prosser-Loose, Erin J; Smith, Shari E; Paterson, Phyllis G

    2011-05-01

    Protein-energy malnutrition (PEM) affects ~16% of patients at admission for stroke. We previously modeled this in a gerbil global cerebral ischemia model and found that PEM impairs functional outcome and influences mechanisms of ischemic brain injury and recovery. Since this model is no longer reliable, we investigated the utility of the rat 2-vessel occlusion (2-VO) with hypotension model of global ischemia for further study of this clinical problem. Male, Sprague-Dawley rats were exposed to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7d prior to either global ischemia or sham surgery. PEM did not significantly alter the hippocampal CA1 neuron death (p = 0.195 by 2-factor ANOVA) or the increase in dendritic injury caused by exposure to global ischemia. Unexpectedly, however, a strong trend was evident for PEM to decrease the consistency of hippocampal damage, as shown by an increased incidence of unilateral or no hippocampal damage (p=0.069 by chi-square analysis). Although PEM caused significant changes to baseline arterial blood pH, pO(2), pCO(2), and fasting glucose (p0.269). Intra-ischemic tympanic temperature and blood pressure were strictly and equally controlled between ischemic groups. We conclude that co-existing PEM confounded the consistency of hippocampal injury in the 2-VO model. Although the mechanisms responsible were not identified, this model of brain ischemia should not be used for studying this co-morbidity factor. © 2011 Bentham Science Publishers Ltd.

  2. Brain protection by methylprednisolone in rats with spinal cord injury.

    Science.gov (United States)

    Chang, Chia-Mao; Lee, Ming-Hsueh; Wang, Ting-Chung; Weng, Hsu-Huei; Chung, Chiu-Yen; Yang, Jen-Tsung

    2009-07-01

    Traumatic spinal cord injury is clinically treated by high doses of methylprednisolone. However, the effect of methylprednisolone on the brain in spinal cord injury patients has been little investigated. This experimental study examined Bcl-2 and Bax protein expression and Nissl staining to evaluate an apoptosis-related intracellular signaling event and final neuron death, respectively. Spinal cord injury produced a significant apoptotic change and cell death not only in the spinal cord but also in the supraventricular cortex and hippocampal cornu ammonis 1 region in the rat brains. The treatment of methylprednisolone increased the Bcl-2/Bax ratio and prevented neuron death for 1-7 days after spinal cord injury. These findings suggest that rats with spinal cord injury show ascending brain injury that could be restricted through methylprednisolone management.

  3. Deformation-Based Atrophy Estimation for Alzheimer’s Disease

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru

    Alzheimer’s disease (AD) - the most common form of dementia, is a term used for accelerated memory loss and cognitive abilities enough to severely hamper day-to-day activities. One of the most globally accepted markers for AD is atrophy, in mainly the brain parenchyma. The goal of the PhD project...... and a new way to estimate atrophy from a deformation field. We demonstrate the performance of the proposed solution but applying it on the publicly available Alzheimer’s disease neuroimaging data (ADNI) initiative and compare to existing state-of-art atrophy estimation methods....

  4. Orphan disease: Cherubism, optic atrophy, and short stature.

    Science.gov (United States)

    Jeevanandham, Balaji; Ramachandran, Rajoo; Dhanapal, Vignesh; Subramanian, Ilanchezhian; Sai, Venkata

    2018-01-01

    A 12-year-old female presented with complaints of progressive visual impairment in both her eyes. On clinical examination, she was short for her age and her ophthalmoscopic examination revealed bilateral optic atrophy. Computed tomography of the patient revealed multiple expansile lytic lesions of mandible suggesting cherubism. The optic atrophy was confirmed on magnetic resonance imaging, which additionally revealed bilateral retrocerebellar arachnoid cysts. This association of cherubism with optic atrophy and short stature was grouped as orphan disease by National Institutes of Health and only one case was reported in the literature so far.

  5. Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.

    Science.gov (United States)

    Durand, Paul D; Couto, Rafael A; Isakov, Raymond; Yoo, Donald B; Azizzadeh, Babak; Guyuron, Bahman; Zins, James E

    2016-04-01

    While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  6. Accelerating regional atrophy rates in the progression from normal aging to Alzheimer's disease

    International Nuclear Information System (INIS)

    Sluimer, Jasper D.; Flier, Wiesje M. van der; Scheltens, Philip; Karas, Giorgos B.; Barkhof, Frederik; Schijndel, Ronald van; Barnes, Josephine; Boyes, Richard G.; Cover, Keith S.; Olabarriaga, Silvia D.; Fox, Nick C.; Vrenken, Hugo

    2009-01-01

    We investigated progression of atrophy in vivo, in Alzheimer's disease (AD), and mild cognitive impairment (MCI). We included 64 patients with AD, 44 with MCI and 34 controls with serial MRI examinations (interval 1.8 ± 0.7 years). A nonlinear registration algorithm (fluid) was used to calculate atrophy rates in six regions: frontal, medial temporal, temporal (extramedial), parietal, occipital lobes and insular cortex. In MCI, the highest atrophy rate was observed in the medial temporal lobe, comparable with AD. AD patients showed even higher atrophy rates in the extramedial temporal lobe. Additionally, atrophy rates in frontal, parietal and occipital lobes were increased. Cox proportional hazard models showed that all regional atrophy rates predicted conversion to AD. Hazard ratios varied between 2.6 (95% confidence interval (CI) = 1.1-6.2) for occipital atrophy and 15.8 (95% CI = 3.5-71.8) for medial temporal lobe atrophy. In conclusion, atrophy spreads through the brain with development of AD. MCI is marked by temporal lobe atrophy. In AD, atrophy rate in the extramedial temporal lobe was even higher. Moreover, atrophy rates also accelerated in parietal, frontal, insular and occipital lobes. Finally, in nondemented elderly, medial temporal lobe atrophy was most predictive of progression to AD, demonstrating the involvement of this region in the development of AD. (orig.)

  7. Value of extent of hippocampal resection in the surgical treatment of temporal lobe epilepsy Valor da extensão da ressecção do hipocampo no tratamento cirúrgico da epilepsia de lobo temporal

    Directory of Open Access Journals (Sweden)

    Leonardo Bonilha

    2004-03-01

    Full Text Available OBJECTIVE: Unilateral hippocampal atrophy is indicator of good surgical prognosis in patients with temporal lobe epilepsy (TLE. Some patients however do not become seizure free after surgery. We assessed if the extent of hippocampal and amygdala resection is associated with outcome. METHODS: Thirty patients with TLE with unilateral or clearly asymmetric hippocampal atrophy who underwent surgical treatment were evaluated concerning preoperative clinical variables and interictal EEG abnormalities. Amygdala and hippocampal resection was evaluated by post-operative MRI. We compared seizure free versus non-seizure free patients, and patients with good outcome (Engel's classes I and II versus patients with poor outcome. RESULTS: There was significant association between the extent of hippocampal resection and the outcome. Pre-operative variables and interictal EEG abnormalities did not show relationship with outcome as documented in previous studies. CONCLUSION: The extent of hippocampal resection is associated with outcome. Incomplete resection of atrophic hippocampus may explain most surgical failures in patients with TLE due to unilateral hippocampal sclerosis.OBJETIVO: A atrofia hipocampal unilateral é indicadora de bom prognóstico cirúrgico em pacientes com epilepsia do lobo temporal (ELT. Alguns pacientes, no entanto, não se tornam livres de crises após a cirurgia. Nós avaliamos se i o EEG interictal e ii a extensão da ressecção do hipocampo e da amígdala estão associados com resultado cirúrgico. MÉTODO: Trinta pacientes com ELT com atrofia hipocampal unilateral ou claramente assimétrica que se submeteram a tratamento cirúrgico foram avaliados quanto a variáveis clínicas pré-operatórias e anormalidades ao EEG interictal. A ressecção da amídala e do hipocampo foi avaliada pela ressonância magnética pós-operatória. Nós comparamos os pacientes livres de crises com os pacientes não livres de crises, e os pacientes com bom

  8. Hippocampal Sclerosis in Older Patients

    Science.gov (United States)

    Cykowski, Matthew D.; Powell, Suzanne Z.; Schulz, Paul E.; Takei, Hidehiro; Rivera, Andreana L.; Jackson, Robert E.; Roman, Gustavo; Jicha, Gregory A.; Nelson, Peter T.

    2018-01-01

    Context Autopsy studies of the older population (≥65 years of age), and particularly of the “oldest-old” (≥85 years of age), have identified a significant proportion (~20%) of cognitively impaired patients in which hippocampal sclerosis is the major substrate of an amnestic syndrome. Hippocampal sclerosis may also be comorbid with frontotemporal lobar degeneration, Alzheimer disease, and Lewy body disease. Until recently, the terms hippocampal sclerosis of aging or hippocampal sclerosis dementia were applied in this context. Recent discoveries have prompted a conceptual expansion of hippocampal sclerosis of aging because (1) cellular inclusions of TAR DNA-binding protein 43 kDa (TDP-43) are frequent; (2) TDP-43 pathology may be found outside hippocampus; and (3) brain arteriolosclerosis is a common, possibly pathogenic, component. Objective To aid pathologists with recent recommendations for diagnoses of common neuropathologies in older persons, particularly hippocampal sclerosis, and highlight the recent shift in diagnostic terminology from HS-aging to cerebral age-related TDP-43 with sclerosis (CARTS). Data Sources Peer-reviewed literature and 5 autopsy examples that illustrate common age-related neuropathologies, including CARTS, and emphasize the importance of distinguishing CARTS from late-onset frontotemporal lobar degeneration with TDP-43 pathology and from advanced Alzheimer disease with TDP-43 pathology. Conclusions In advanced old age, the substrates of cognitive impairment are often multifactorial. This article demonstrates common and frequently comorbid neuropathologic substrates of cognitive impairment in the older population, including CARTS, to aid those practicing in this area of pathology. PMID:28467211

  9. Effect of docosahexaenoic acid on hippocampal neurons in high-glucose condition: involvement of PI3K/AKT/nuclear factor-κB-mediated inflammatory pathways.

    Science.gov (United States)

    Yang, R-H; Lin, J; Hou, X-H; Cao, R; Yu, F; Liu, H-Q; Ji, A-L; Xu, X-N; Zhang, L; Wang, F

    2014-08-22

    Accumulating evidence suggested that hyperglycemia played a critical role in hippocampus dysfunction in patients with diabetes mellitus. However, the multifactorial pathogenesis of hyperglycemia-induced impairments of hippocampal neurons has not been fully elucidated. Docosahexaenoic acid (DHA) has been shown to enhance learning and memory and affect neural function in various experimental conditions. The present study investigated the effects of DHA on the lipid peroxidation, the level of inflammatory cytokines and neuron apoptosis in the hippocampal neurons in high-glucose condition. High-glucose administration increased the level of tumor necrosis factor α (TNF-α) and IL-6, induced oxidative stress and apoptosis of hippocampal neurons in vitro. DHA treatment reduced oxidative stress and TNF-α expression, protected the hippocampal neurons by increasing AKT phosphorylation and decreasing caspase-3 and caspase-9 expression. These results suggested that high-glucose exposure induced injury of hippocampal neurons in vitro, and the principle mechanisms involved in the neuroprotective effect of DHA were its antioxidant and anti-apoptotic potential. DHA may thus be of use in preventing or treating neuron-degeneration resulting from hyperglycemia. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Brain atrophy during aging. Quantitative studies with X-CT and NMR-CT

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzawa, Taiju; Yamada, Kenji; Yamada, Susumu; Ono, Shuichi; Takeda, Shunpei; Hatazawa, Jun; Ito, Masatoshi; Kubota, Kazuo

    1985-12-01

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT. Brain atrophy was minimal in 34-35 years old in both sexes, increased exponentially to the increasing age after 34-35 years, and probably resulted in dementia, such as vascular or multi-infarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34-35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extent of brain atrophy (20 - 30 %) existed among aged subjects. Progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was the decrease in the cerebral blood flow. We have classified brain atrophy into sulcal and cisternal enlargement type (type I), ventricular enlargement type (type II) and mixed type (type III) according to the clinical study using NMR-CT. Brain atrophy of type I progresses significantly in almost all of the geriatric disorders. This type of brain atrophy progresses significantly in heavy smokers and drinkers. Therefore this type of brain atrophy might be caused by the decline in the blood flow in anterior and middle cerebral arteries. Brain atrophy of type II was caused by the disturbance of cerebrospinal fluid circulation after cerebral bleeding and subarachnoid bleeding. Brain atrophy of type III was seen in vascular dementia or multi-infarct dementia which was caused by loss of brain matter after multiple infarction, and was seen also in dementia of Alzheimer type in which degeneration of nerve cells results in brain atrophy. NMR-CT can easily detect small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy. (J.P.N.).

  11. Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat

    Science.gov (United States)

    Hanlon, Lauren A.; Huh, Jimmy W.

    2016-01-01

    Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312

  12. Albumin infusion after reperfusion prevents gut ischemia-reperfusion-induced gut-associated lymphoid tissue atrophy.

    Science.gov (United States)

    Ikezawa, Fumie; Fukatsu, Kazuhiko; Moriya, Tomoyuki; Maeshima, Yoshinori; Okamoto, Koichi; Hara, Etsuko; Hiraide, Hoshio; Compher, Charlene W

    2006-01-01

    Our recent study clarified that gut ischemia-reperfusion (I/R) causes gut-associated lymphoid tissue (GALT) mass atrophy, a possible mechanism for increased morbidity of infectious complications after severe surgical insults. Because albumin administration reportedly reduces hemorrhagic shock-induced lung injury, we hypothesized that albumin treatment prevents GALT atrophy due to gut I/R. Male mice (n = 37) were randomized to albumin, normal saline, and sham groups. All groups underwent jugular vein catheter insertion. The albumin and normal saline groups underwent 75-minute occlusion of the superior mesenteric artery. During gut ischemia, all mice received normal saline infusions at 1.0 mL/h. The albumin group was given 5% bovine serum albumin in normal saline at 1.0 mL/h for 60 minutes after reperfusion, whereas the normal saline group received 0.9% sodium chloride at 1.0 mL/h. The sham group underwent laparotomy only. Mice were killed on day 1 or 7, and the entire small intestine was harvested. GALT lymphocytes were isolated and counted. Their phenotypes (alphabetaTCR, gammadeltaTCR, CD4, CD8, B220) were determined by flow cytometry. On day 1, the gut I/R groups showed significantly lower total lymphocyte and B cell numbers in Peyer's patches and the lamina propria than the sham group. However, the albumin infusion partially but significantly restored these cell numbers. On day 7, there were no significant differences in any of the parameters measured among the 3 groups. Albumin infusion after a gut ischemic insult may maintain gut immunity by preventing GALT atrophy.

  13. Parahippocampal Involvement in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis: A Proof of Concept from Memory-Guided Saccades

    Directory of Open Access Journals (Sweden)

    Silvia Colnaghi

    2017-11-01

    Full Text Available ObjectiveMesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS may involve extrahippocampal areas of structural damage and dysfunction. The accuracy of medium-term spatial memory can be tested by memory-guided saccades (MGS to evaluate a functional impairment of the parahippocampal cortex (PHC, while voxel-based morphometry (VBM analysis can be used to detect a structural damage of the latter region.MethodsMGS with 3- and 30-s memorization delays were compared between 7 patients affected by right MTLE-HS (r-MTLE-HS, 6 patients affected by left MTLE-HS, and 13 healthy controls. The same subjects underwent brain MRI for a VBM analysis. Correlation analysis was performed between the results of VBM and MGS and with patients’ clinical data.ResultsRight MTLE-HS patients showed impaired accuracy of leftward MGS with a 30-s memorization delay; their gray-matter volume was reduced in the right hippocampus and inferior temporal gyrus, and bilaterally in the cerebellum. Left MTLE-HS patients had normal MGS accuracy; their gray-matter volume was reduced in the left hippocampus, in the right-inferior temporal gyrus and corpus callosus, and bilaterally in the insular cortex and in the cerebellum. The difference between right and left parahippocampal volumes correlated with MGS accuracy, while right and left hippocampal volumes did not. Hippocampal and parahippocampal volume did not correlate with clinical variables such as febrile seizures, age at disease onset, disease duration, and seizure frequency.ConclusionMGS abnormalities suggested the functional involvement of the right PHC in patients with r-MTLE-HS, supporting a right lateralization of spatial memory control and showing a relation between functional impairment and degree of atrophy.

  14. Orphan disease: Cherubism, optic atrophy, and short stature

    Directory of Open Access Journals (Sweden)

    Balaji Jeevanandham

    2018-01-01

    Full Text Available A 12-year-old female presented with complaints of progressive visual impairment in both her eyes. On clinical examination, she was short for her age and her ophthalmoscopic examination revealed bilateral optic atrophy. Computed tomography of the patient revealed multiple expansile lytic lesions of mandible suggesting cherubism. The optic atrophy was confirmed on magnetic resonance imaging, which additionally revealed bilateral retrocerebellar arachnoid cysts. This association of cherubism with optic atrophy and short stature was grouped as orphan disease by National Institutes of Health and only one case was reported in the literature so far.

  15. Early and Degressive Putamen Atrophy in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Julia Krämer

    2015-09-01

    Full Text Available Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS. Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS. 68 patients with RRMS and 26 healthy controls (HC were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (ICV. Patient’s relative putamen volume (RPV, expressed in percent of ICV, was significantly reduced compared to HC. Based on the correlation between RPV and age, we computed the age-corrected RPV deviation (ΔRPV from HC. Patients showed significantly negative ΔRPV. Interestingly, the age-corrected ΔRPV depended logarithmically on disease duration: Directly after first symptom manifestation, patients already showed a reduced RPV followed by a further degressive volumetric decline. This means that atrophy progression was stronger in the first than in later years of disease. Putamen atrophy starts directly after initial symptom manifestation or even years before, and progresses in a degressive manner. Due to its important role in neurological functions, early detection of putamen atrophy seems necessary. High-resolution structural MRI allows monitoring of disease course.

  16. Neurofibrillary tangle pathology and Braak staging in chronic epilepsy in relation to traumatic brain injury and hippocampal sclerosis: a post-mortem study.

    Science.gov (United States)

    Thom, Maria; Liu, Joan Y W; Thompson, Pam; Phadke, Rahul; Narkiewicz, Marta; Martinian, Lillian; Marsdon, Derek; Koepp, Matthias; Caboclo, Luis; Catarino, Claudia B; Sisodiya, Sanjay M

    2011-10-01

    The long-term pathological effects of chronic epilepsy on normal brain ageing are unknown. Previous clinical and epidemiological studies show progressive cognitive decline in subsets of patients and an increased prevalence of Alzheimer's disease in epilepsy. In a post-mortem series of 138 patients with long-term, mainly drug-resistant epilepsy, we carried out Braak staging for Alzheimer's disease neurofibrillary pathology using tau protein immunohistochemistry. The stages were compared with clinicopathological factors, including seizure history and presence of old traumatic brain injury. Overall, 31% of cases were Braak Stage 0, 36% Stage I/II, 31% Stage III/IV and 2% Stage V/VI. The mean age at death was 56.5 years and correlated with Braak stage (P < 0.001). Analysis of Braak stages within age groups showed a significant increase in mid-Braak stages (III/IV), in middle age (40-65 years) compared with data from an ageing non-epilepsy series (P < 0.01). There was no clear relationship between seizure type (generalized or complex partial), seizure frequency, age of onset and duration of epilepsy with Braak stage although higher Braak stages were noted with focal more than with generalized epilepsy syndromes (P < 0.01). In 30% of patients, there was pathological evidence of traumatic brain injury that was significantly associated with higher Braak stages (P < 0.001). Cerebrovascular disease present in 40.3% and cortical malformations in 11.3% were not significantly associated with Braak stage. Astrocytic-tau protein correlated with the presence of both traumatic brain injury (P < 0.01) and high Braak stage (P < 0.001). Hippocampal sclerosis, identified in 40% (bilateral in 48%), was not associated with higher Braak stages, but asymmetrical patterns of tau protein accumulation within the sclerotic hippocampus were noted. In over half of patients with cognitive decline, the Braak stage was low indicating causes other than Alzheimer's disease pathology. In summary

  17. The Impacts of Swimming Exercise on Hippocampal Expression of Neurotrophic Factors in Rats Exposed to Chronic Unpredictable Mild Stress

    Directory of Open Access Journals (Sweden)

    Pei Jiang

    2014-01-01

    Full Text Available Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were involved in the antidepressive effects of exercise, in this study, we assessed the effects of swimming exercise on hippocampal mRNA expression of several classes of the growth factors (BDNF, GDNF, NGF, NT-3, FGF2, VEGF, and IGF-1 and peptides (VGF and NPY in rats exposed to chronic unpredictable mild stress (CUMS. Our study demonstrated that the swimming training paradigm significantly induced the expression of BDNF and BDNF-regulated peptides (VGF and NPY and restored their stress-induced downregulation. Additionally, the exercise protocol also increased the antiapoptotic Bcl-xl expression and normalized the CUMS mediated induction of proapoptotic Bax mRNA level. Overall, our data suggest that swimming exercise has antidepressant effects, increasing the resistance to the neural damage caused by CUMS, and both BDNF and its downstream neurotrophic peptides may exert a major function in the exercise related adaptive processes to CUMS.

  18. Hippocampal sclerosis in advanced age: clinical and pathological features

    Science.gov (United States)

    Schmitt, Frederick A.; Lin, Yushun; Abner, Erin L.; Jicha, Gregory A.; Patel, Ela; Thomason, Paula C.; Neltner, Janna H.; Smith, Charles D.; Santacruz, Karen S.; Sonnen, Joshua A.; Poon, Leonard W.; Gearing, Marla; Green, Robert C.; Woodard, John L.; Van Eldik, Linda J.; Kryscio, Richard J.

    2011-01-01

    Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer’s disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer’s Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n = 106). For individuals aged ≥95 years at death (n = 179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of ‘definite’ Alzheimer’s disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n = 10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar

  19. Hippocampal sclerosis in advanced age: clinical and pathological features.

    Science.gov (United States)

    Nelson, Peter T; Schmitt, Frederick A; Lin, Yushun; Abner, Erin L; Jicha, Gregory A; Patel, Ela; Thomason, Paula C; Neltner, Janna H; Smith, Charles D; Santacruz, Karen S; Sonnen, Joshua A; Poon, Leonard W; Gearing, Marla; Green, Robert C; Woodard, John L; Van Eldik, Linda J; Kryscio, Richard J

    2011-05-01

    Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer's disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer's Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n=106). For individuals aged≥95 years at death (n=179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of 'definite' Alzheimer's disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n=10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR

  20. Predictive modeling of neuroanatomic structures for brain atrophy detection

    Science.gov (United States)

    Hu, Xintao; Guo, Lei; Nie, Jingxin; Li, Kaiming; Liu, Tianming

    2010-03-01

    In this paper, we present an approach of predictive modeling of neuroanatomic structures for the detection of brain atrophy based on cross-sectional MRI image. The underlying premise of applying predictive modeling for atrophy detection is that brain atrophy is defined as significant deviation of part of the anatomy from what the remaining normal anatomy predicts for that part. The steps of predictive modeling are as follows. The central cortical surface under consideration is reconstructed from brain tissue map and Regions of Interests (ROI) on it are predicted from other reliable anatomies. The vertex pair-wise distance between the predicted vertex and the true one within the abnormal region is expected to be larger than that of the vertex in normal brain region. Change of white matter/gray matter ratio within a spherical region is used to identify the direction of vertex displacement. In this way, the severity of brain atrophy can be defined quantitatively by the displacements of those vertices. The proposed predictive modeling method has been evaluated by using both simulated atrophies and MRI images of Alzheimer's disease.

  1. Homotaurine Effects on Hippocampal Volume Loss and Episodic Memory in Amnestic Mild Cognitive Impairment.

    Science.gov (United States)

    Spalletta, Gianfranco; Cravello, Luca; Gianni, Walter; Piras, Federica; Iorio, Mariangela; Cacciari, Claudia; Casini, Anna Rosa; Chiapponi, Chiara; Sancesario, Giuseppe; Fratangeli, Claudia; Orfei, Maria Donata; Caltagirone, Carlo; Piras, Fabrizio

    2016-01-01

    Homotaurine supplementation may have a positive effect on early Alzheimer's disease. Here, we investigated its potential neuroprotective effect on the hippocampus structure and episodic memory performances in amnestic mild cognitive impairment (aMCI). Neuropsychological, clinical, and neuroimaging assessment in 11 treated and 22 untreated patients were performed at baseline and after 1 year. Magnetic resonance data were analyzed using voxel-based morphometry to explore significant differences (Family Wise Error corrected) between the two groups over time. Patients treated with homotaurine showed decreased volume loss in the left and right hippocampal tail, left and right fusiform gyrus, and right inferior temporal cortex which was associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall. Thus, homotaurine supplementation in individuals with aMCI has a positive effect on hippocampus atrophy and episodic memory loss. Future studies should further clarify the mechanisms of its effects on brain morphometry.

  2. Different atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Millino Caterina

    2009-04-01

    Full Text Available Abstract Background Spinal muscular atrophy (SMA is a neurodegenerative disorder associated with mutations of the survival motor neuron gene SMN and is characterized by muscle weakness and atrophy caused by degeneration of spinal motor neurons. SMN has a role in neurons but its deficiency may have a direct effect on muscle tissue. Methods We applied microarray and quantitative real-time PCR to study at transcriptional level the effects of a defective SMN gene in skeletal muscles affected by the two forms of SMA: the most severe type I and the mild type III. Results The two forms of SMA generated distinct expression signatures: the SMA III muscle transcriptome is close to that found under normal conditions, whereas in SMA I there is strong alteration of gene expression. Genes implicated in signal transduction were up-regulated in SMA III whereas those of energy metabolism and muscle contraction were consistently down-regulated in SMA I. The expression pattern of gene networks involved in atrophy signaling was completed by qRT-PCR, showing that specific pathways are involved, namely IGF/PI3K/Akt, TNF-α/p38 MAPK and Ras/ERK pathways. Conclusion Our study suggests a different picture of atrophy pathways in each of the two forms of SMA. In particular, p38 may be the regulator of protein synthesis in SMA I. The SMA III profile appears as the result of the concurrent presence of atrophic and hypertrophic fibers. This more favorable condition might be due to the over-expression of MTOR that, given its role in the activation of protein synthesis, could lead to compensatory hypertrophy in SMA III muscle fibers.

  3. Traumatic intracranial hemorrhage correlates with preinjury brain atrophy, but not with antithrombotic agent use: a retrospective study.

    Directory of Open Access Journals (Sweden)

    C Michael Dunham

    Full Text Available The impact of antithrombotic agents (warfarin, clopidogrel, ASA on traumatic brain injury outcomes is highly controversial. Although cerebral atrophy is speculated as a risk for acute intracranial hemorrhage, there is no objective literature evidence.This is a retrospective, consecutive investigation of patients with signs of external head trauma and age ≥60 years. Outcomes were correlated with antithrombotic-agent status, coagulation test results, admission neurologic function, and CT-based cerebral atrophy dimensions.Of 198 consecutive patients, 36% were antithrombotic-negative and 64% antithrombotic-positive. ASA patients had higher arachidonic acid inhibition (p = 0.04 and warfarin patients had higher INR (p<0.001, compared to antithrombotic-negative patients. Antithrombotic-positive intracranial hemorrhage rate (38.9% was similar to the antithrombotic-negative rate (31.9%; p = 0.3285. Coagulopathy was not present on the ten standard coagulation, thromboelastography, and platelet mapping tests with intracranial hemorrhage and results were similar to those without hemorrhage (p≥0.1354. Hemorrhagic-neurologic complication (intracranial hemorrhage progression, need for craniotomy, neurologic deterioration, or death rates were similar for antithrombotic-negative (6.9% and antithrombotic-positive (8.7%; p = 0.6574 patients. The hemorrhagic-neurologic complication rate was increased when admission major neurologic dysfunction was present (63.2% versus 2.2%; RR = 28.3; p<0.001. Age correlated inversely with brain parenchymal width (p<0.001 and positively with lateral ventricular width (p = 0.047 and cortical atrophy (p<0.001. Intracranial hemorrhage correlated with cortical atrophy (p<0.001 and ventricular width (p<0.001.Intracranial hemorrhage is not associated with antithrombotic agent use. Intracranial hemorrhage patients have no demonstrable coagulopathy. The association of preinjury brain atrophy with acute intracranial

  4. Correlating learning and memory improvements to long-term potentiation in patients with brain injury

    Institute of Scientific and Technical Information of China (English)

    Xingfu Peng; Qian Yu

    2008-01-01

    patients clinically present with various manifestations,such as paralysis and sensory disability,which closely correlate to injured regions.In addition,learning and memory abilities decrease in brain injury patients and LTP decreases following brain injury.Brain tissue injury will lead to brain functional deficits. Hippocampal LTP is very sensitive.Difficulties in LTP induction are apparent even prior to morphological changes in brain tissue.There are no specific treatments for learning and memory functional deficits following brain injury.At present,behavioral and compensative therapies are the typical forms of rehabilitation.These results indicate that rehabilitation promotes learning and memory functional recovery in brain injury patients by speeding up LTP formation in the hippocampal CA3 region.CONCLUSION:Rehabilitation intervention increases LTP formation in the hippocampal CA3 region and recovers learning and memory functions in brain injury patients.

  5. A case of hepatic atrophy by irradiation

    International Nuclear Information System (INIS)

    Fukumoto, Takumi; Ku, Yonson; Saitoh, Yoichi

    1994-01-01

    A 44-year-old woman was treated with 60 Co irradiation (total dose 6000 rads) focused on the right side porta hepatis under the diagnosis of cholangiocarcinoma in 1975. Seventeen years after the treatment, she was admitted to our institution because of dull pain at right hypochondriac region. Adominal CT demonstrated an extreme hepatic atrophy and tumor mass in the right lobe of the liver. In November, 1991 right trisegmentectomy was performed under the diagnosis of hepatocellular carcinoma. Laparotomy revealed the extreme atrophy of the right lobe and associated hypertrophy of the left lobe of the liver. In this case radiation hepatitis occurred after irradiation to the liver and it was followed by the extreme hepatic atrophy as a long term effect of high dose irradiation on the liver. (author)

  6. Biochemical adaptations of antigravity muscle fibers to disuse atrophy

    Science.gov (United States)

    Booth, F. W.

    1978-01-01

    Studies are presented in four parts of this report. The four parts include; (1) studies to gain information on the molecular basis of atrophy by antigravity muscle; (2) studies on the work capacity of antigravity muscles during atrophy and during recovery from atrophy; (3) studies on recovery of degenerated antigravity fibers after removal of hind-limb casts; and (4) studies on the atrophy and recovery of bone. The philosophy of these studies was to identify the time sequence of events in the soleus muscle of the rat following immobilization of the hind limbs, so that the length of the soleus muscle within the fixed limb is less than its resting length. In two separate studies, no decline in the weight of the soleus muscle could be detected during the first 72 hours of limb immobilization.

  7. Cerebral blood flow and brain atrophy correlated by xenon contrast CT scanning

    International Nuclear Information System (INIS)

    Kitagawa, Y.; Meyer, J.S.; Tanahashi, N.; Rogers, R.L.; Tachibana, H.; Kandula, P.; Dowell, R.E.; Mortel, K.F.

    1985-01-01

    Correlations between cerebral blood flow (CBF) measured during stable xenon contrast CT scanning and standard CT indices of brain atrophy were investigated in the patients with senile dementia of Alzheimer type, multi-infarct dementia and idiopathic Parkinson's disease. Compared to age-matched normal volunteers, significant correlations were found in patients with idiopathic Parkinson's disease between cortical and subcortical gray matter blood flow and brain atrophy estimated by the ventricular body ratio, and mild to moderate brain atrophy were correlated with stepwise CBF reductions. However, in patients with senile dementia of Alzheimer type and multi-infarct dementia, brain atrophy was not associated with stepwise CBF reductions. Overall correlations between brain atrophy and reduced CBF were weak. Mild degrees of brain atrophy are not always associated with reduced CBF

  8. Effect of Oenothera odorata Root Extract on Microgravity and Disuse-Induced Muscle Atrophy.

    Science.gov (United States)

    Lee, Yong-Hyeon; Seo, Dong-Hyun; Park, Ji-Hyung; Kabayama, Kazuya; Opitz, Joerg; Lee, Kwang Ho; Kim, Han-Sung; Kim, Tack-Joong

    2015-01-01

    Muscle atrophy, a reduction of muscle mass, strength, and volume, results from reduced muscle use and plays a key role in various muscular diseases. In the microgravity environment of space especially, muscle atrophy is induced by muscle inactivity. Exposure to microgravity induces muscle atrophy through several biological effects, including associations with reactive oxygen species (ROS). This study used 3D-clinostat to investigate muscle atrophy caused by oxidative stress in vitro, and sciatic denervation was used to investigate muscle atrophy in vivo. We assessed the effect of Oenothera odorata root extract (EVP) on muscle atrophy. EVP helped recover cell viability in C2C12 myoblasts exposed to microgravity for 24 h and delayed muscle atrophy in sciatic denervated mice. However, the expressions of HSP70, SOD1, and ceramide in microgravity-exposed C2C12 myoblasts and in sciatic denervated mice were either decreased or completely inhibited. These results suggested that EVP can be expected to have a positive effect on muscle atrophy by disuse and microgravity. In addition, EVP helped characterize the antioxidant function in muscle atrophy.

  9. MRI of the spinocerebellar degeneration (multiple system atrophy, Holmes type, and Menzel-Joseph type)

    International Nuclear Information System (INIS)

    Mukai, Eiichiro; Makino, Naoki.

    1991-01-01

    We have analyzed MRI in 33 patients with several forms of spinocerebellar degeneration; 17 with multiple system atrophy, 10 with Holmes type, and 6 with Menzel-Joseph type. The MRIs were obtained using a 1.5-T GEMR System. Patients with multiple system atrophy demonstrated: atrophy of the brain stem, particularly basis pontis; decreased signal intensity of the white matter of pons; atrophy of the white matter of cerebellum; atrophy and decreased signal intensity of the putamen, particularly along their lateral and posterior portions; and atrophy of the cerebrum. Patients with Holmes type showed: atrophy of the cerebellum; atrophy of the vermis more than hemispheres; and nuclei of the cerebellum with no decreased intensity on T 2 -weighted sequences. Patients with Menzel-Joseph type demonstrated moderate atrophy of the brain stem and mild atrophy of the white matter of cerebellum. MRI is a useful diagnostic tool in the management of the spinocerebellar degeneration. (author)

  10. Efficacy, Dosage, and Duration of Action of Branched Chain Amino Acid Therapy for Traumatic Brain Injury

    Science.gov (United States)

    Elkind, Jaclynn A.; Lim, Miranda M.; Johnson, Brian N.; Palmer, Chris P.; Putnam, Brendan J.; Kirschen, Matthew P.; Cohen, Akiva S.

    2015-01-01

    Traumatic brain injury (TBI) results in long-lasting cognitive impairments for which there is currently no accepted treatment. A well-established mouse model of mild to moderate TBI, lateral fluid percussion injury (FPI), shows changes in network excitability in the hippocampus including a decrease in net synaptic efficacy in area CA1 and an increase in net synaptic efficacy in dentate gyrus. Previous studies identified a novel therapy consisting of branched chain amino acids (BCAAs), which restored normal mouse hippocampal responses and ameliorated cognitive impairment following FPI. However, the optimal BCAA dose and length of treatment needed to improve cognitive recovery is unknown. In the current study, mice underwent FPI then consumed 100 mM BCAA supplemented water ad libitum for 2, 3, 4, 5, and 10 days. BCAA therapy ameliorated cognitive impairment at 5 and 10 days duration. Neither BCAA supplementation at 50 mM nor BCAAs when dosed 5 days on then 5 days off was sufficient to ameliorate cognitive impairment. These results suggest that brain injury causes alterations in hippocampal function, which underlie and contribute to hippocampal cognitive impairment, which are reversible with at least 5 days of BCAA treatment, and that sustaining this effect is dependent on continuous treatment. Our findings have profound implications for the clinical investigation of TBI therapy. PMID:25870584

  11. Efficacy, dosage and duration of action of branched chain amino acid therapy for traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Jaclynn eElkind

    2015-03-01

    Full Text Available Traumatic brain injury (TBI results in long-lasting cognitive impairments for which there is currently no accepted treatment. A well-established mouse model of mild to moderate TBI, lateral fluid percussion injury (FPI, shows changes in network excitability in the hippocampus including a decrease in net synaptic efficacy in area CA1 and an increase in net synaptic efficacy in dentate gyrus. Previous studies identified a novel therapy consisting of branched chain amino acids (BCAAs which restored normal mouse hippocampal responses and ameliorated cognitive impairment following FPI. However, the optimal BCAA dose and length of treatment needed to improve cognitive recovery is unknown. In the current study mice underwent FPI then consumed 100 mM BCAA supplemented water ad libitum for 2, 3, 4, 5 and 10 days. BCAA therapy ameliorated cognitive impairment at 5 and 10 days duration. Neither BCAA supplementation at 50 mM, nor BCAAs when dosed 5 days on then 5 days off, was sufficient to ameliorate cognitive impairment. These results suggest that brain injury causes alterations in hippocampal function which underlie and contribute to hippocampal cognitive impairment which are reversible with at least 5 days of BCAA treatment, and that sustaining this effect is dependent on continuous treatment. Our findings have profound implications for the clinical investigation of TBI therapy.

  12. Bacteremia causes hippocampal apoptosis in experimental pneumococcal meningitis

    DEFF Research Database (Denmark)

    Andersen, Christian Østergaard; Leib, S.L.; Rowland, Ian J

    2010-01-01

    ABSTRACT: BACKGROUND: Bacteremia and systemic complications both play important roles in brain pathophysiological alterations and the outcome of pneumococcal meningitis. Their individual contributions to the development of brain damage, however, still remain to be defined. METHODS: Using an adult...... rat pneumococcal meningitis model, the impact of bacteremia accompanying meningitis on the development of hippocampal injury was studied. The study comprised of the three groups: I. Meningitis (n=11), II. meningitis with attenuated bacteremia resulting from iv injection of serotype......-specific pneumococcal antibodies (n=14), and III. uninfected controls (n=6). RESULTS: Pneumococcal meningitis resulted in a significantly higher apoptosis score 0.22 (0.18-0.35) compared to uninfected controls (0.02 (0.00-0.02), Mann Whitney test, P=0.0003). Also, meningitis with an attenuation of bacteremia...

  13. Reviewing the options for local estrogen treatment of vaginal atrophy

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    Lindahl SH

    2014-03-01

    Full Text Available Sarah H Lindahl Sutter East Bay Medical Foundation, SEBMF – Diablo Division, Castro Valley, CA, USA Background: Vaginal atrophy is a chronic condition with symptoms that include vaginal dryness, pain during sex, itching, irritation, burning, and discharge, as well as various urinary problems. Up to 45% of postmenopausal women may be affected, but it often remains underreported and undertreated. This article aims to review the current recommendations for treatment of vaginal atrophy, and current data on the effectiveness and safety of local vaginal estrogen therapies. Methods: Literature regarding vaginal atrophy (2007–2012 was retrieved from PubMed and summarized, with emphasis on data related to the treatment of vaginal atrophy with local vaginal estrogen therapy. Results: Published data support the effectiveness and endometrial safety of low-dose local estrogen therapies. These results further support the general recommendation by the North American Menopause Society that a progestogen is not needed for endometrial protection in patients using low-dose local vaginal estrogen. Benefits of long-term therapy for vaginal atrophy include sustained relief of symptoms as well as physiological improvements (eg, decreased vaginal pH and increased blood flow, epithelial thickness, secretions. Conclusion: Currently available local vaginal estrogen therapies are well tolerated and effective in relieving symptoms of vaginal atrophy. Recent data support the endometrial safety of low-dose regimens for up to 1 year. Keywords: menopause, estrogen, local estrogen therapy, vaginal atrophy

  14. Hippocampal dosimetry correlates with the change in neurocognitive function after hippocampal sparing during whole brain radiotherapy: a prospective study

    International Nuclear Information System (INIS)

    Tsai, Ping-Fang; Yang, Chi-Cheng; Chuang, Chi-Cheng; Huang, Ting-Yi; Wu, Yi-Ming; Pai, Ping-Ching; Tseng, Chen-Kan; Wu, Tung-Ho; Shen, Yi-Liang; Lin, Shinn-Yn

    2015-01-01

    Whole brain radiotherapy (WBRT) has been the treatment of choice for patients with brain metastases. However, change/decline of neurocognitive functions (NCFs) resulting from impaired hippocampal neurogenesis might occur after WBRT. It is reported that conformal hippocampal sparing would provide the preservation of NCFs. Our study aims to investigate the hippocampal dosimetry and to demonstrate the correlation between hippocampal dosimetry and neurocognitive outcomes in patients receiving hippocampal sparing during WBRT (HS-WBRT). Forty prospectively recruited cancer patients underwent HS-WBRT for therapeutic or prophylactic purposes. Before receiving HS-WBRT, all participants received a battery of baseline neurocognitive assessment, including memory, executive functions and psychomotor speed. The follow-up neurocognitive assessment at 4 months after HS-WBRT was also performed. For the delivery of HS-WBRT, Volumetric Modulated Arc Therapy (VMAT) with two full arcs and two non-coplanar partial arcs was employed. For each treatment planning, dose volume histograms were generated for left hippocampus, right hippocampus, and the composite hippocampal structure respectively. Biologically equivalent doses in 2-Gy fractions (EQD 2 ) assuming an alpha/beta ratio of 2 Gy were computed. To perform analyses addressing the correlation between hippocampal dosimetry and the change in scores of NCFs, pre- and post-HS-WBRT neurocognitive assessments were available in 24 patients in this study. Scores of NCFs were quite stable before and after HS-WBRT in terms of hippocampus-dependent memory. Regarding verbal memory, the corresponding EQD 2 values of 0, 10, 50, 80 % irradiating the composite hippocampal structure with <12.60 Gy, <8.81, <7.45 Gy and <5.83 Gy respectively were significantly associated with neurocognitive preservation indicated by the immediate recall of Word List Test of Wechsler Memory Scale-III. According to logistic regression analyses, it was noted that

  15. CT findings of brain atrophy after chemotherapy in acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jun; Park, Seog Hee; Kim, Choon Yul; Bahk, Yong Whee [Catholic University Medicine College, Seoul (Korea, Republic of)

    1988-10-15

    A study was performed to evaluate the atrophic changes of the central nerve system after chemotherapy in the patients with acute leukemia. The computed tomographic findings and medical records of 20 proven acute leukemia patients under 35 years-old who developed various CNS symptoms and signs during and/or after 2 courses of chemotherapy were reviewed. The results were as follows: 1. Age distribution was from 14 to 5 years (mean was 26 years). Male was 15. 2. Presenting clinical symptoms and signs were headache (16/20), nausea and vomiting (11/20) and loss of consciousness (5/20). 3. Brain atrophy was noted in 16 patients including cortical and subcortical atrophy 15 cases and subcortical atrophy 1 case. 4. Two cases of hemorrhage, one each of intracranial hematoma and chronic subdural hematoma were found in addition to brain atrophy. This showed that chemotherapeutic agents cause brain atrophy in a considerable number of the patients with symptomatic acute leukemia.

  16. Targeted inhibition of TGF-β results in an initial improvement but long-term deficit in force production after contraction-induced skeletal muscle injury.

    Science.gov (United States)

    Gumucio, Jonathan P; Flood, Michael D; Phan, Anthony C; Brooks, Susan V; Mendias, Christopher L

    2013-08-15

    Transforming growth factor-β (TGF-β) is a proinflammatory cytokine that regulates the response of many tissues following injury. Previous studies in our lab have shown that treating muscles with TGF-β results in a dramatic accumulation of type I collagen, substantial fiber atrophy, and a marked decrease in force production. Because TGF-β promotes atrophy and fibrosis, our objective was to investigate whether the inhibition of TGF-β after injury would enhance the recovery of muscle following injury. We hypothesized that inhibiting TGF-β after contraction-induced injury would improve the functional recovery of muscles by preventing muscle fiber atrophy and weakness, and by limiting the accumulation of fibrotic scar tissue. To test this hypothesis, we induced an injury using a series of in situ lengthening contractions to extensor digitorum longus muscles of mice treated with either a bioneutralizing antibody against TGF-β or a sham antibody. Compared with controls, muscles from mice receiving TGF-β inhibitor showed a greater recovery in force 3 days and 7 days after injury but had a decrease in force compared with controls at the 21-day time point. The early enhancement in force in the TGF-β inhibitor group was associated with an initial improvement in tissue morphology, but, at 21 days, while the control group was fully recovered, the TGF-β inhibitor group displayed an irregular extracellular matrix and an increase in atrogin-1 gene expression. These results indicate that the inhibition of TGF-β promotes the early recovery of muscle function but is detrimental overall to full muscle recovery following moderate to severe muscle injuries.

  17. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy.

    Science.gov (United States)

    Shakespeare, Timothy J; Kaski, Diego; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Ryan, Natalie S; Schott, Jonathan M; Crutch, Sebastian J

    2015-07-01

    The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal 'visual dementia' and most common atypical Alzheimer's disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients' (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer's disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer's disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer's disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with 'sticky fixation'. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer's disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large saccadic intrusions

  18. Imaging of patients with hippocampal sclerosis at 7 Tesla: initial results.

    Science.gov (United States)

    Breyer, Tobias; Wanke, Isabel; Maderwald, Stefan; Woermann, Friedrich G; Kraff, Oliver; Theysohn, Jens M; Ebner, Alois; Forsting, Michael; Ladd, Mark E; Schlamann, Marc

    2010-04-01

    Focal epilepsies potentially can be cured by neurosurgery; other treatment options usually remain symptomatic. High-resolution magnetic resonance (MR) imaging is the central imaging strategy in the evaluation of focal epilepsy. The most common substrate of temporal epilepsies is hippocampal sclerosis (HS), which cannot always be sufficiently characterized with current MR field strengths. Therefore, the purpose of our study was to demonstrate the feasibility of high-resolution MR imaging at 7 Tesla in patients with focal epilepsy resulting from a HS and to improve image resolution at 7 Tesla in patients with HS. Six patients with known HS were investigated with T1-, T2-, T2(*)-, and fluid-attenuated inversion recovery-weighted sequences at 7 Tesla with an eight-channel transmit-receive head coil. Total imaging time did not exceed 90 minutes per patient. High-resolution imaging at 7 Tesla is feasible and reveals high resolution of intrahippocampal structures in vivo. HS was confirmed in all patients. The maximum non-interpolated in-plane resolution reached 0.2 x 0.2 mm(2) in T2(*)-weighted images. The increased susceptibility effects at 7 Tesla revealed identification of intrahippocampal structures in more detail than at 1.5 Tesla, but otherwise led to stronger artifacts. Imaging revealed regional differences in hippocampal atrophy between patients. The scan volume was limited because of specific absorption rate restrictions, scanning time was reasonable. High-resolution imaging at 7 Tesla is promising in presurgical epilepsy imaging. "New" contrasts may further improve detection of even very small intrahippocampal structural changes. Therefore, further investigations will be necessary to demonstrate the potential benefit for presurgical selection of patients with various lesion patterns in mesial temporal epilepsies resulting from a unilateral HS. Copyright 2010 AUR. Published by Elsevier Inc. All rights reserved.

  19. Alzheimer's Disease Diagnostic Performance of a Multi-Atlas Hippocampal Segmentation Method using the Harmonized Hippocampal Protocol

    DEFF Research Database (Denmark)

    Anker, Cecilie Benedicte; Sørensen, Lauge; Pai, Akshay

    PURPOSE Hippocampal volumetry is the most widely used structural MRI biomarker of Alzheimer’s disease (AD), and state-of-the-art, automatic hippocampal segmentation can be obtained using longitudinal FreeSurfer. In this study, we compare the diagnostic AD performance of a single time point, multi...

  20. Novel in vitro platform to investigate myotube atrophy.

    Science.gov (United States)

    Oelkrug, Christopher; Horn, Katharina; Makert, Gustavo R; Schubert, Andreas

    2015-04-01

    The electrical current exclusion (ECE) principle provides an alternative to common methods of cell diameter measurement and especially in atrophy and cancer associated cachexia research. C2C12 myoblasts were differentiated into myotubes and treated with 100 μM dexamethasone to induce atrophy in vitro. Subsequently, they were incubated for 24 h with media containing different concentrations of curcumin and/or branched-chain amino acids (BCAAs) in order to counteract atrophy. After treatment with curcumin, an increase in cell diameter was detectable; the highest increase with 13.9 ± 0.4% was seen with 10 μM curcumin. The combination of curcumin and BCAAs showed an increase of 13.4 ± 1.2 %. Cell diameter measurement via the ECE showed that curcumin, and curcumin in combination with BCAAs, were able to restore atrophic C2C12 myotubes. Therefore, the application of ECE in muscle atrophy and also cancer-associated cachexia research allows rapid screening of novel compounds in order to test their efficacy in vitro. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Hippocampal volume change measurement: quantitative assessment of the reproducibility of expert manual outlining and the automated methods FreeSurfer and FIRST.

    Science.gov (United States)

    Mulder, Emma R; de Jong, Remko A; Knol, Dirk L; van Schijndel, Ronald A; Cover, Keith S; Visser, Pieter J; Barkhof, Frederik; Vrenken, Hugo

    2014-05-15

    To measure hippocampal volume change in Alzheimer's disease (AD) or mild cognitive impairment (MCI), expert manual delineation is often used because of its supposed accuracy. It has been suggested that expert outlining yields poorer reproducibility as compared to automated methods, but this has not been investigated. To determine the reproducibilities of expert manual outlining and two common automated methods for measuring hippocampal atrophy rates in healthy aging, MCI and AD. From the Alzheimer's Disease Neuroimaging Initiative (ADNI), 80 subjects were selected: 20 patients with AD, 40 patients with mild cognitive impairment (MCI) and 20 healthy controls (HCs). Left and right hippocampal volume change between baseline and month-12 visit was assessed by using expert manual delineation, and by the automated software packages FreeSurfer (longitudinal processing stream) and FIRST. To assess reproducibility of the measured hippocampal volume change, both back-to-back (BTB) MPRAGE scans available for each visit were analyzed. Hippocampal volume change was expressed in μL, and as a percentage of baseline volume. Reproducibility of the 1-year hippocampal volume change was estimated from the BTB measurements by using linear mixed model to calculate the limits of agreement (LoA) of each method, reflecting its measurement uncertainty. Using the delta method, approximate p-values were calculated for the pairwise comparisons between methods. Statistical analyses were performed both with inclusion and exclusion of visibly incorrect segmentations. Visibly incorrect automated segmentation in either one or both scans of a longitudinal scan pair occurred in 7.5% of the hippocampi for FreeSurfer and in 6.9% of the hippocampi for FIRST. After excluding these failed cases, reproducibility analysis for 1-year percentage volume change yielded LoA of ±7.2% for FreeSurfer, ±9.7% for expert manual delineation, and ±10.0% for FIRST. Methods ranked the same for reproducibility of 1

  2. Effect of Oenothera odorata Root Extract on Microgravity and Disuse-Induced Muscle Atrophy

    Directory of Open Access Journals (Sweden)

    Yong-Hyeon Lee

    2015-01-01

    Full Text Available Muscle atrophy, a reduction of muscle mass, strength, and volume, results from reduced muscle use and plays a key role in various muscular diseases. In the microgravity environment of space especially, muscle atrophy is induced by muscle inactivity. Exposure to microgravity induces muscle atrophy through several biological effects, including associations with reactive oxygen species (ROS. This study used 3D-clinostat to investigate muscle atrophy caused by oxidative stress in vitro, and sciatic denervation was used to investigate muscle atrophy in vivo. We assessed the effect of Oenothera odorata root extract (EVP on muscle atrophy. EVP helped recover cell viability in C2C12 myoblasts exposed to microgravity for 24 h and delayed muscle atrophy in sciatic denervated mice. However, the expressions of HSP70, SOD1, and ceramide in microgravity-exposed C2C12 myoblasts and in sciatic denervated mice were either decreased or completely inhibited. These results suggested that EVP can be expected to have a positive effect on muscle atrophy by disuse and microgravity. In addition, EVP helped characterize the antioxidant function in muscle atrophy.

  3. Astrocyte atrophy and immune dysfunction in self-harming macaques.

    Science.gov (United States)

    Lee, Kim M; Chiu, Kevin B; Sansing, Hope A; Inglis, Fiona M; Baker, Kate C; MacLean, Andrew G

    2013-01-01

    Self-injurious behavior (SIB) is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP) and Toll-like receptor 2 (TLR2). Morphologic features of astrocytes were determined using computer-assisted camera lucida. There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

  4. Astrocyte atrophy and immune dysfunction in self-harming macaques.

    Directory of Open Access Journals (Sweden)

    Kim M Lee

    Full Text Available BACKGROUND: Self-injurious behavior (SIB is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. METHODS: We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP and Toll-like receptor 2 (TLR2. Morphologic features of astrocytes were determined using computer-assisted camera lucida. RESULTS: There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. CONCLUSIONS: These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

  5. Asymmetrical hippocampal connectivity in mesial temporal lobe epilepsy: evidence from resting state fMRI

    Directory of Open Access Journals (Sweden)

    Castellano Gabriela

    2010-06-01

    Full Text Available Abstract Background Mesial temporal lobe epilepsy (MTLE, the most common type of focal epilepsy in adults, is often caused by hippocampal sclerosis (HS. Patients with HS usually present memory dysfunction, which is material-specific according to the hemisphere involved and has been correlated to the degree of HS as measured by postoperative histopathology as well as by the degree of hippocampal atrophy on magnetic resonance imaging (MRI. Verbal memory is mostly affected by left-sided HS, whereas visuo-spatial memory is more affected by right HS. Some of these impairments may be related to abnormalities of the network in which individual hippocampus takes part. Functional connectivity can play an important role to understand how the hippocampi interact with other brain areas. It can be estimated via functional Magnetic Resonance Imaging (fMRI resting state experiments by evaluating patterns of functional networks. In this study, we investigated the functional connectivity patterns of 9 control subjects, 9 patients with right MTLE and 9 patients with left MTLE. Results We detected differences in functional connectivity within and between hippocampi in patients with unilateral MTLE associated with ipsilateral HS by resting state fMRI. Functional connectivity resulted to be more impaired ipsilateral to the seizure focus in both patient groups when compared to control subjects. This effect was even more pronounced for the left MTLE group. Conclusions The findings presented here suggest that left HS causes more reduction of functional connectivity than right HS in subjects with left hemisphere dominance for language.

  6. Hippocampal MR volumetry

    Science.gov (United States)

    Haller, John W.; Botteron, K.; Brunsden, Barry S.; Sheline, Yvette I.; Walkup, Ronald K.; Black, Kevin J.; Gado, Mokhtar; Vannier, Michael W.

    1994-09-01

    Goal: To estimate hippocampal volumes from in vivo 3D magnetic resonance (MR) brain images and determine inter-rater and intra- rater repeatability. Objective: The precision and repeatability of hippocampal volume estimates using stereologic measurement methods is sought. Design: Five normal control and five schizophrenic subjects were MR scanned using a MPRAGE protocol. Fixed grid stereologic methods were used to estimate hippocampal volumes on a graphics workstation. The images were preprocessed using histogram analysis to standardize 3D MR image scaling from 16 to 8 bits and image volumes were interpolated to 0.5 mm3 isotropic voxels. The following variables were constant for the repeated stereologic measures: grid size, inter-slice distance (1.5 mm), voxel dimensions (0.5 mm3), number of hippocampi measured (10), total number of measurements per rater (40), and number of raters (5). Two grid sizes were tested to determine the coefficient of error associated with the number of sampled 'hits' (approximately 140 and 280) on the hippocampus. Starting slice and grid position were randomly varied to assure unbiased volume estimates. Raters were blind to subject identity, diagnosis, and side of the brain from which the image volumes were extracted and the order of subject presentation was randomized for each of the raters. Inter- and intra-rater intraclass correlation coefficients (ICC) were determined. Results: The data indicate excellent repeatability of fixed grid stereologic hippocampal volume measures when using an inter-slice distance of 1.5 mm and a 6.25 mm2 grid (inter-rater ICCs equals 0.86 - 0.97, intra- rater ICCs equals 0.85 - 0.97). One major advantage of the current study was the use of 3D MR data which significantly improved visualization of hippocampal boundaries by providing the ability to access simultaneous orthogonal views while counting stereological marks within the hippocampus. Conclusion: Stereological estimates of 3D volumes from 2D MR

  7. Spinal Muscular Atrophy FAQ

    Science.gov (United States)

    ... as ALS (Lou Gehrig’s Disease), cystic fibrosis and Duchenne muscular dystrophy. Approximately 1 in 50 Americans, or about 6 ... Pediatric Neuromuscular Clinical Research Network ( PNCR ) and the Muscular ... is the SMN2 gene? Muscle weakness and atrophy in SMA results from the ...

  8. Radiation-induced brain injury: A review

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    Michael eRobbins

    2012-07-01

    Full Text Available Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (> 6 months to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses > 30 Gy; white matter necrosis occurs at fractionated doses > 60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain

  9. A novel method of quantifying brain atrophy associated with age-related hearing loss

    Directory of Open Access Journals (Sweden)

    Z. Jason Qian

    2017-01-01

    Audiometric evaluations and mini-mental state exams were obtained in 34 subjects over the age of 80 who have had brain MRIs in the past 6 years. CSF and parenchymal brain volumes (whole brain and by lobe were obtained through a novel, fully automated algorithm. Atrophy was calculated by taking the ratio of CSF to parenchyma. High frequency hearing loss was associated with disproportional temporal lobe atrophy relative to whole brain atrophy independent of age (r = 0.471, p = 0.005. Mental state was associated with frontoparietal atrophy but not to temporal lobe atrophy, which is consistent with known results. Our method demonstrates that hearing loss is associated with temporal lobe atrophy and generalized whole brain atrophy. Our algorithm is efficient, fully automated, and able to detect significant associations in a small cohort.

  10. A case of dentato-rubro-pallido-luysian atrophy

    International Nuclear Information System (INIS)

    Usui, Sadanari; Komiya, Tadatoshi

    1988-01-01

    A clinical case of dentato-rubro-pallido-luysian atrophy (DRPLA) was reported. We established several aspects on the basis of MRI findings and a neuro-otological study. A 47-year-old woman had gait disturbance, involuntary movements, speech disturbance, and memory disturbance at the age of 42. She was admitted to the hospital because of worsening of the gait disturbance. Neurological examinations showed choreo-athetosis of the face, neck and upper extremities, mental disturbance, and scanning speech. However, she had neither ocular disturbance nor epilepsy or myoclonus. On the MRI-CT, an atrophy of midbrain and pontine tegmentum was observed. The neuro-otological study showed gaze nystagmus at the horizontal gaze, rebound nystagmus, hypometria of the saccade, saccadic pursuit, reduction of the optokinetic nystagmus, and increase in caloric nystagmus by means of visual input. A severe atrophy of the brainstem tegmentum and a mild atrophy of the cerebellar hemisphere and cerebral cortex are regarded as neuro-radiological features of DRPLA. Moreover, tegmental atrophy is related to ocular disturbance as a clinical feature. Various neuro-otological findings reveal many systems of ocular movements, i.e., a smooth pursuit system, a saccade system, and a vestibulo-ocular reflex system, involving flocculus. DRPLA can be clinically diagnosed by means of clinical features, MRI findings, and neuro-otological findings. A variety of neuro-otological abnormalities may indicate a progression of the ocular disturbance and a variety of lesions. (author)

  11. DDPH ameliorated oxygen and glucose deprivation-induced injury in rat hippocampal neurons via interrupting Ca2+ overload and glutamate release.

    Science.gov (United States)

    He, Zhi; Lu, Qing; Xu, Xulin; Huang, Lin; Chen, Jianguo; Guo, Lianjun

    2009-01-28

    Our previous work has demonstrated that DDPH (1-(2, 6-dimethylphenoxy)-2-(3, 4-dimethoxyphenylethylamino) propane hydrochloride), a competitive alpha(1)-adrenoceptor antagonist, could improve cognitive deficits, reduce histopathological damage and facilitate synaptic plasticity in vivo possibly via increasing NR2B (NMDA receptor 2B) expression and antioxidation of DDPH itself. The present study further evaluated effects of DDPH on OGD (Oxygen and glucose deprivation)-induced neuronal damage in rat primary hippocampal cells. The addition of DDPH to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and LDH (lactate dehydrogenase) release experiments. The effects of DDPH on intracellular calcium concentration were explored by Fura-2 based calcium imaging techniques and results showed that DDPH at the dosages of 5 microM and 10 microM suppressed the increase of intracellular calcium ([Ca(2+)](i)) stimulated by 50 mM KCl in Ca(2+)-containing extracellular solutions. However, DDPH couldn't suppress the increase of [Ca(2+)](i) induced by both 50 microM glutamate in Ca(2+)-containing extracellular solutions and 20 microM ATP (Adenosine Triphosphate) in Ca(2+)-free solution. These results indicated that DDPH prevented [Ca(2+)](i) overload in hippocampal neurons by blocking Ca(2+) influx (voltage-dependent calcium channel) but not Ca(2+) mobilization from the intracellular Ca(2+) store in endoplasm reticulum (ER). We also demonstrated that DDPH could decrease glutamate release when hippocampal cells were subjected to OGD. These observations demonstrated that DDPH protected hippocampal neurons against OGD-induced damage by preventing the Ca(2+) influx and decreasing glutamate release.

  12. Cortisol, Cytokines, and Hippocampal Volume in the Elderly

    Directory of Open Access Journals (Sweden)

    Keith Daniel Sudheimer

    2014-07-01

    Full Text Available Separate bodies of literature report that elevated pro-inflammatory cytokines and cortisol negatively affect hippocampal structure and cognitive functioning, particularly in older adults. Although interactions between cytokines and cortisol occur through a variety of known mechanisms, few studies consider how their interactions affect brain structure. In this preliminary study, we assess the impact of interactions between circulating levels of IL-1Beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha, and waking cortisol on hippocampal volume. Twenty-eight community-dwelling older adults underwent blood draws for quantification of circulating cytokines and saliva collections to quantify the cortisol awakening response. Hippocampal volume measurements were made using structural magnetic resonance imaging. Elevated levels of waking cortisol in conjunction with higher concentrations of IL-6 and TNF-alpha were associated with smaller hippocampal volumes. In addition, independent of cortisol, higher levels of IL-1beta and TNF-alpha were also associated with smaller hippocampal volumes. These data provide preliminary evidence that higher cortisol, in conjunction with higher IL-6 and TNF-alpha, are associated with smaller hippocampal volume in older adults. We suggest that the dynamic balance between the hypothalamic-pituitary adrenal axis and inflammation processes may explain hippocampal volume reductions in older adults better than either set of measures do in isolation.

  13. Effects of exposure to high glucose on primary cultured hippocampal neurons: involvement of intracellular ROS accumulation.

    Science.gov (United States)

    Liu, Di; Zhang, Hong; Gu, Wenjuan; Zhang, Mengren

    2014-06-01

    Recent studies showed that hyperglycemia is the main trigger of diabetic cognitive impairment and can cause hippocampus abnormalities. The goal of this study is to explore the effects of different concentrations of high glucose for different exposure time on cell viability as well as intracellular reactive oxygen species (ROS) generation of primary cultured hippocampal neurons. Hippocampal neurons were exposed to different concentrations of high glucose (50, 75, 100, 125, and 150 mM) for 24, 48, 72 and 96 h. Cell viability and nuclear morphology were evaluated by MTT and Hoechst assays, respectively. Intracellular ROS were monitored using the fluorescent probe DCFH-DA. The results showed that, compared with control group, the cell viability of all high glucose-treated groups decreased significantly after 72 h and there also was a significant increase of apoptotic nuclei in high glucose-treated groups from 72 to 96 h. Furthermore, 50 mM glucose induced a peak rise in ROS generation at 24 h and the intracellular ROS levels of 50 mM glucose group were significantly higher than the corresponding control group from 6 to 72 h. These results suggest that hippocampal neurons could be injured by high glucose exposure and the neuronal injury induced by high glucose is potentially mediated through intracellular ROS accumulation.

  14. Hippocampal sclerosis in children younger than 2 years

    Energy Technology Data Exchange (ETDEWEB)

    Kadom, Nadja [Children' s National Medical Center, Department of Diagnostic Imaging and Radiology, Washington, DC (United States); Tsuchida, Tammy; Gaillard, William D. [Children' s National Medical Center, Department of Neurology, Washington, DC (United States)

    2011-10-15

    Hippocampal sclerosis (HS) is rarely considered as a diagnosis in children younger than 2 years. To describe imaging features in conjunction with clinical information in patients with hippocampal sclerosis who are younger than 2 years. We retrospectively reviewed MR brain imaging and clinical information in five children in whom the diagnosis of HS was made both clinically and by MRI prior to 2 years of age. Imaging features establishing the diagnosis of hippocampal sclerosis were bright T2 signal and volume loss, while the internal architecture of the hippocampal formation was preserved in almost all children. Clinically, all children had an infectious trigger. It is necessary for radiologists to consider HS in children with certain clinical features to plan an MRI protocol that is appropriate for detection of hippocampal pathology. (orig.)

  15. Hippocampal sclerosis in children younger than 2 years

    International Nuclear Information System (INIS)

    Kadom, Nadja; Tsuchida, Tammy; Gaillard, William D.

    2011-01-01

    Hippocampal sclerosis (HS) is rarely considered as a diagnosis in children younger than 2 years. To describe imaging features in conjunction with clinical information in patients with hippocampal sclerosis who are younger than 2 years. We retrospectively reviewed MR brain imaging and clinical information in five children in whom the diagnosis of HS was made both clinically and by MRI prior to 2 years of age. Imaging features establishing the diagnosis of hippocampal sclerosis were bright T2 signal and volume loss, while the internal architecture of the hippocampal formation was preserved in almost all children. Clinically, all children had an infectious trigger. It is necessary for radiologists to consider HS in children with certain clinical features to plan an MRI protocol that is appropriate for detection of hippocampal pathology. (orig.)

  16. Tensor-Based Morphometry Reveals Volumetric Deficits in Moderate=Severe Pediatric Traumatic Brain Injury.

    Science.gov (United States)

    Dennis, Emily L; Hua, Xue; Villalon-Reina, Julio; Moran, Lisa M; Kernan, Claudia; Babikian, Talin; Mink, Richard; Babbitt, Christopher; Johnson, Jeffrey; Giza, Christopher C; Thompson, Paul M; Asarnow, Robert F

    2016-05-01

    Traumatic brain injury (TBI) can cause widespread and prolonged brain degeneration. TBI can affect cognitive function and brain integrity for many years after injury, often with lasting effects in children, whose brains are still immature. Although TBI varies in how it affects different individuals, image analysis methods such as tensor-based morphometry (TBM) can reveal common areas of brain atrophy on magnetic resonance imaging (MRI), secondary effects of the initial injury, which will differ between subjects. Here we studied 36 pediatric moderate to severe TBI (msTBI) participants in the post-acute phase (1-6 months post-injury) and 18 msTBI participants who returned for their chronic assessment, along with well-matched controls at both time-points. Participants completed a battery of cognitive tests that we used to create a global cognitive performance score. Using TBM, we created three-dimensional (3D) maps of individual and group differences in regional brain volumes. At both the post-acute and chronic time-points, the greatest group differences were expansion of the lateral ventricles and reduction of the lingual gyrus in the TBI group. We found a number of smaller clusters of volume reduction in the cingulate gyrus, thalamus, and fusiform gyrus, and throughout the frontal, temporal, and parietal cortices. Additionally, we found extensive associations between our cognitive performance measure and regional brain volume. Our results indicate a pattern of atrophy still detectable 1-year post-injury, which may partially underlie the cognitive deficits frequently found in TBI.

  17. Computed tomography of skeletal muscles in childhood spinal progressive muscular atrophies

    International Nuclear Information System (INIS)

    Arai, Yumi; Osawa, Makiko; Sumida, Sawako; Shishikura, Keiko; Suzuki, Haruko; Fukuyama, Yukio; Kohno, Atsushi

    1992-01-01

    Computed tomographic (CT) scanning of skeletal muscles was performed in patients with type 1 and type 2 spinal progressive muscular atrophy (SPMA) and Kugelberg-Welander disease (K-W) to delineate the characteristic CT features of each category. Marked muscular atrophy was observed in type 1 SPMA, and both muscular atrophy and intramuscular low density areas in type 2 SPMA, changes being more pronounced in older patients. In contrast, in K-W, muscular atrophy was slight, and intramuscular low density areas constituted the most prominent findings. These observations indicate that SPMA and K-W are each characterized by distinct CT findings. (author)

  18. Is the Supraspinatus Muscle Atrophy Truly Irreversible after Surgical Repair of Rotator Cuff Tears?

    Science.gov (United States)

    Chung, Seok Won; Kim, Sae Hoon; Tae, Suk-Kee; Yoon, Jong Pil; Choi, Jung-Ah

    2013-01-01

    Background Atrophy of rotator cuff muscles has been considered an irreversible phenomenon. The purpose of this study is to evaluate whether atrophy is truly irreversible after rotator cuff repair. Methods We measured supraspinatus muscle atrophy of 191 patients with full-thickness rotator cuff tears on preoperative magnetic resonance imaging and postoperative multidetector computed tomography images, taken at least 1 year after operation. The occupation ratio was calculated using Photoshop CS3 software. We compared the change between pre- and postoperative occupation ratios after modifying the preoperative occupation ratio. In addition, possible relationship between various clinical factors and the change of atrophy, and between the change of atrophy and cuff integrity after surgical repair were evaluated. Results The mean occupation ratio was significantly increased postoperatively from 0.44 ± 0.17 to 0.52 ± 0.17 (p < 0.001). Among 191 patients, 81 (42.4%) showed improvement of atrophy (more than a 10% increase in occupation ratio) and 33 (17.3%) worsening (more than a 10% decrease). Various clinical factors such as age tear size, or initial degree of atrophy did not affect the change of atrophy. However, the change of atrophy was related to repair integrity: cuff healing failure rate of 48.5% (16 of 33) in worsened atrophy; and 22.2% (18 of 81) in improved atrophy (p = 0.007). Conclusions The supraspinatus muscle atrophy as measured by occupation ratio could be improved postoperatively in case of successful cuff repair. PMID:23467404

  19. Daily oral intake of theanine prevents the decline of 5-bromo-2′-deoxyuridine incorporation in hippocampal dentate gyrus with concomitant alleviation of behavioral abnormalities in adult mice with severe traumatic stress

    Directory of Open Access Journals (Sweden)

    Takeshi Takarada

    2015-03-01

    Full Text Available Posttraumatic stress disorder is a long-lasting psychiatric disease with the consequence of hippocampal atrophy in humans exposed to severe fatal stress. We demonstrated a positive correlation between the transient decline of 5-bromo-2′-deoxyuridine (BrdU incorporation in the hippocampal dentate gyrus (DG and long-lasting behavioral abnormalities in mice with traumatic stress. Here, we investigated pharmacological properties of theanine on the declined BrdU incorporation and abnormal behaviors in mice with traumatic stress. Prior daily oral administration of theanine at 50–500 mg/kg for 5 days significantly prevented the decline of BrdU incorporation, while theanine significantly prevented the decline in the DG even when administered for 5 days after stress. Consecutive daily administration of theanine significantly inhibited the prolonged immobility in mice with stress in forced swimming test seen 14 days later. Although traumatic stress significantly increased spontaneous locomotor activity over 30 min even when determined 14 days later, the increased total locomotion was significantly ameliorated following the administration of theanine at 50 mg/kg for 14 days after stress. These results suggest that theanine alleviates behavioral abnormalities together with prevention of the transient decline of BrdU incorporation in the hippocampal DG in adult mice with severe traumatic stress.

  20. Can endurance exercise preconditioning prevention disuse muscle atrophy?

    Directory of Open Access Journals (Sweden)

    Michael P Wiggs

    2015-03-01

    Full Text Available Emerging evidence suggests that exercise training can provide a level of protection against disuse muscle atrophy. Endurance exercise training imposes oxidative, metabolic, and heat stress on skeletal muscle which activates a variety of cellular signaling pathways that ultimately leads to the increased expression of proteins that have been demonstrated to protect muscle from inactivity –induced atrophy. This review will highlight the effect of exercise-induced oxidative stress on endogenous enzymatic antioxidant capacity (i.e., superoxide dismutase, glutathione peroxidase, and catalase, the role of oxidative and metabolic stress on PGC1-α, and finally highlight the effect heat stress and HSP70 induction. Finally, this review will discuss the supporting scientific evidence that these proteins can attenuate muscle atrophy through exercise preconditioning.

  1. Accelerating regional atrophy rates in the progression from normal aging to Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Sluimer, Jasper D. [VU University Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Diagnostic Radiology and Alzheimer Centre, PO Box 7057, Amsterdam (Netherlands); Flier, Wiesje M. van der; Scheltens, Philip [VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Neurology, Amsterdam (Netherlands); Karas, Giorgos B.; Barkhof, Frederik [VU University Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); Schijndel, Ronald van [VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Informatics, Amsterdam (Netherlands); Barnes, Josephine; Boyes, Richard G. [UCL, Institute of Neurology, Dementia Research Centre, London (United Kingdom); Cover, Keith S. [VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands); Olabarriaga, Silvia D. [University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam (Netherlands); Fox, Nick C. [VU University Medical Centre, Department of Neurology, Amsterdam (Netherlands); UCL, Institute of Neurology, Dementia Research Centre, London (United Kingdom); Vrenken, Hugo [VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands)

    2009-12-15

    We investigated progression of atrophy in vivo, in Alzheimer's disease (AD), and mild cognitive impairment (MCI). We included 64 patients with AD, 44 with MCI and 34 controls with serial MRI examinations (interval 1.8 {+-} 0.7 years). A nonlinear registration algorithm (fluid) was used to calculate atrophy rates in six regions: frontal, medial temporal, temporal (extramedial), parietal, occipital lobes and insular cortex. In MCI, the highest atrophy rate was observed in the medial temporal lobe, comparable with AD. AD patients showed even higher atrophy rates in the extramedial temporal lobe. Additionally, atrophy rates in frontal, parietal and occipital lobes were increased. Cox proportional hazard models showed that all regional atrophy rates predicted conversion to AD. Hazard ratios varied between 2.6 (95% confidence interval (CI) = 1.1-6.2) for occipital atrophy and 15.8 (95% CI = 3.5-71.8) for medial temporal lobe atrophy. In conclusion, atrophy spreads through the brain with development of AD. MCI is marked by temporal lobe atrophy. In AD, atrophy rate in the extramedial temporal lobe was even higher. Moreover, atrophy rates also accelerated in parietal, frontal, insular and occipital lobes. Finally, in nondemented elderly, medial temporal lobe atrophy was most predictive of progression to AD, demonstrating the involvement of this region in the development of AD. (orig.)

  2. Neuropsychological correlates of brain atrophy in Huntington's disease: a magnetic resonance imaging study

    International Nuclear Information System (INIS)

    Starkstein, S.E.; Brandt, J.; Bylsma, F.; Peyser, C.; Folstein, M.; Folstein, S.E.

    1992-01-01

    Magnetic resonance imaging and a comprehensive cognitive evaluation were carried out in a series of 29 patients with mild to moderate Huntington's disease (HD). A factor analysis of the neuropsychological test scores provided three factors: A memory/speed-of-processing factor, a 'frontal' factor, and a response inhibition factor. The memory/speed factor correlated significantly with measures of caudate atrophy, frontal atrophy, and atrophy of the left (but not the right) sylvian cistern. There were no significant correlations between the 'frontal' or response inhibition factors and measures of cortical or subcortical brain atrophy. Our findings confirm that subcortical atrophy is significantly correlated with specific cognitive deficits in HD, and demonstrate that cortical atrophy also has important association with the cognitive deficits of patients with HD. (orig.)

  3. Benefits of Laser Therapy in Postmenopausal Vaginal Atrophy

    Science.gov (United States)

    Brînzan, Daniela; Pǎiuşan, Lucian; Daşcǎu, Voicu; Furǎu, Gheorghe

    2011-08-01

    Maybe the worst aspect of menopause is the decline of the quality of the sexual life. The aim of the study is to demonstrate the beneficial effects of laser therapy in comparison with topical application of estrogen preparations, for the treatment of vaginal atrophy and sexual dysfunctions induced by menopause. A total of 50 menopausal patients were examined during a one year period. The methods used for objectifying vaginal atrophy and sexual dysfunctions were history taking, local clinical exam and PAP smear. From this group, 40 patients had vaginal atrophy with sexual dysfunctions. They have been treated differently, being included in four groups: patients treated with local estrogens, patients treated with intravaginal laser therapy, patients treated with both laser therapy and estrogens, patients treated with estrogens and placebo laser therapy. Therapeutic benefit, improvement of vaginal atrophy and quality of sexual life, were objectified by anamnesis (questionnaire), local and general clinical examination and PAP smear. The best results have been obtained, by far, in the 3rd group, followed by the women treated only with laser. In conclusion, we can say that laser therapy is the best way for solving the sexual inconveniences of menopause.

  4. Genetics Home Reference: spinal muscular atrophy with progressive myoclonic epilepsy

    Science.gov (United States)

    ... myoclonic epilepsy Spinal muscular atrophy with progressive myoclonic epilepsy Printable PDF Open All Close All Enable Javascript ... boxes. Description Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes ...

  5. Inducible satellite cell depletion attenuates skeletal muscle regrowth following a scald-burn injury.

    Science.gov (United States)

    Finnerty, Celeste C; McKenna, Colleen F; Cambias, Lauren A; Brightwell, Camille R; Prasai, Anesh; Wang, Ye; El Ayadi, Amina; Herndon, David N; Suman, Oscar E; Fry, Christopher S

    2017-11-01

    Severe burns result in significant skeletal muscle cachexia that impedes recovery. Activity of satellite cells, skeletal muscle stem cells, is altered following a burn injury and likely hinders regrowth of muscle. Severe burn injury induces satellite cell proliferation and fusion into myofibres with greater activity in muscles proximal to the injury site. Conditional depletion of satellite cells attenuates recovery of myofibre area and volume following a scald burn injury in mice. Skeletal muscle regrowth following a burn injury requires satellite cell activity, underscoring the therapeutic potential of satellite cells in the prevention of prolonged frailty in burn survivors. Severe burns result in profound skeletal muscle atrophy; persistent muscle atrophy and weakness are major complications that hamper recovery from burn injury. Many factors contribute to the erosion of muscle mass following burn trauma, and we have previously shown concurrent activation and apoptosis of muscle satellite cells following a burn injury in paediatric patients. To determine the necessity of satellite cells during muscle recovery following a burn injury, we utilized a genetically modified mouse model (Pax7 CreER -DTA) that allows for the conditional depletion of satellite cells in skeletal muscle. Additionally, mice were provided 5-ethynyl-2'-deoxyuridine to determine satellite cell proliferation, activation and fusion. Juvenile satellite cell-wild-type (SC-WT) and satellite cell-depleted (SC-Dep) mice (8 weeks of age) were randomized to sham or burn injury consisting of a dorsal scald burn injury covering 30% of total body surface area. Both hindlimb and dorsal muscles were studied at 7, 14 and 21 days post-burn. SC-Dep mice had >93% depletion of satellite cells compared to SC-WT (P satellite cell proliferation and fusion. Depletion of satellite cells impaired post-burn recovery of both muscle fibre cross-sectional area and volume (P satellite cells in the aetiology of lean

  6. Atrophy of the corpus callosum correlates with white matter lesions in patients with cerebral ischaemia

    International Nuclear Information System (INIS)

    Meguro, K.; Yamadori, A.; Constans, J.M.; Courtheoux, P.; Theron, J.; Viader, F.

    2000-01-01

    Many studies of white matter high signal (WMHS) on T2-weighted MRI have disclosed that it is related to cerebral ischaemia and to brain atrophy. Atrophy of the corpus callosum (CC) has also been studied in relation to ischaemia. Our objective was to test the hypothesis that CC atrophy could be due to ischaemia. We therefore assessed CC, WMHS and brain atrophy in patients with risk factors without strokes (the risk factor group) and in those with infarcts (the infarct group), to investigate the relationships between these factors. We studied 30 patients in the infarct group, 14 in the risk factor group, and 29 normal subjects. Using axial T1-weighted MRI, cortical atrophy and ventricular enlargement (brain atrophy) were visually rated. Using axial T2-weighted MRI, WMHS was assessed in three categories: periventricular symmetrical, periventricular asymmetrical and subcortical. Using the mid-sagittal T1-weighted image, the CC was measured in its anterior, posterior, midanterior and midposterior portions. In the normal group, no correlations were noted between parameters. In the infarct group, there were significant correlations between CC and brain atrophy, and between CC atrophy and WMHS. After removing the effects of age, gender and brain atrophy, significant correlations were noted between some CC measures and subcortical WMHS. In the risk factor group, there were significant correlations between CC and brain atrophy and between CC atrophy and WMHS. After allowance for age, gender and brain atrophy, significant correlations between some CC measures and periventricular WMHS remained. The hypothesis that CC atrophy could be due to cerebral ischaemia was supported by other analyses. Namely, for correlations between the extent of infarcts and partial CC atrophy in patients with anterior middle cerebral artery (MCA) and with posterior MCA infarcts, there were significant correlations between the extent of infarct and midanterior CC atrophy in the former, and posterior

  7. Atrophy of the corpus callosum correlates with white matter lesions in patients with cerebral ischaemia

    Energy Technology Data Exchange (ETDEWEB)

    Meguro, K.; Yamadori, A. [Section of Neuropsychology, Division of Disability Science, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, 980-8575 Sendai (Japan); Constans, J.M.; Courtheoux, P.; Theron, J. [MR Unit, University of Caen School of Medicine, Caen (France); Viader, F. [Department of Neuroradiology, University of Caen School of Medicine, Caen (France)

    2000-06-01

    Many studies of white matter high signal (WMHS) on T2-weighted MRI have disclosed that it is related to cerebral ischaemia and to brain atrophy. Atrophy of the corpus callosum (CC) has also been studied in relation to ischaemia. Our objective was to test the hypothesis that CC atrophy could be due to ischaemia. We therefore assessed CC, WMHS and brain atrophy in patients with risk factors without strokes (the risk factor group) and in those with infarcts (the infarct group), to investigate the relationships between these factors. We studied 30 patients in the infarct group, 14 in the risk factor group, and 29 normal subjects. Using axial T1-weighted MRI, cortical atrophy and ventricular enlargement (brain atrophy) were visually rated. Using axial T2-weighted MRI, WMHS was assessed in three categories: periventricular symmetrical, periventricular asymmetrical and subcortical. Using the mid-sagittal T1-weighted image, the CC was measured in its anterior, posterior, midanterior and midposterior portions. In the normal group, no correlations were noted between parameters. In the infarct group, there were significant correlations between CC and brain atrophy, and between CC atrophy and WMHS. After removing the effects of age, gender and brain atrophy, significant correlations were noted between some CC measures and subcortical WMHS. In the risk factor group, there were significant correlations between CC and brain atrophy and between CC atrophy and WMHS. After allowance for age, gender and brain atrophy, significant correlations between some CC measures and periventricular WMHS remained. The hypothesis that CC atrophy could be due to cerebral ischaemia was supported by other analyses. Namely, for correlations between the extent of infarcts and partial CC atrophy in patients with anterior middle cerebral artery (MCA) and with posterior MCA infarcts, there were significant correlations between the extent of infarct and midanterior CC atrophy in the former, and posterior

  8. Lycium barbarum polysaccharide protects against oxygen glucose deprivation/reoxygenation-induced apoptosis and autophagic cell death via the PI3K/Akt/mTOR signaling pathway in primary cultured hippocampal neurons.

    Science.gov (United States)

    Yu, Yang; Wu, Xiuquan; Pu, Jingnan; Luo, Peng; Ma, Wenke; Wang, Jiu; Wei, Jialiang; Wang, Yuanxin; Fei, Zhou

    2018-01-01

    Lycium barbarum polysaccharide (LBP) is the main active ingredient of Lycium barbarum, which exhibits several beneficial effects, including neuroprotection, anti-aging and anti-oxidation. However, the mechanism by which LBP protects against cerebral ischemia/reperfusion-induced injury remains obscure. In this study, we found that LBP pretreatment greatly attenuated oxygen glucose deprivation/reperfusion (OGD/R) injury in primary cultured hippocampal neurons. LBP also suppressed OGD/R-induced lactate dehydrogenase (LDH) leakage, and ameliorated oxidative stress. In addition, LBP significantly reduced OGD/R-induced apoptosis and autophagic cell death. LBP caused the down-regulation of cleaved Caspase-3/Caspase-3, LC3II/LC3I and Beclin 1, as well as up-regulation of Bcl-2/Bax and p62. Furthermore, mechanistic studies indicated that LBP pretreatment increased p-Akt and p-mTOR levels after OGD/R. In summary, our results indicated that LBP protects against OGD/R-induced neuronal injury in primary hippocampal neurons by activating the PI3K/Akt/mTOR signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Cellular and molecular mechanisms of muscle atrophy

    Directory of Open Access Journals (Sweden)

    Paolo Bonaldo

    2013-01-01

    Full Text Available Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases.

  10. Crossed cerebellar atrophy in cases with cerebrovascular disease

    International Nuclear Information System (INIS)

    Yagishita, Toshiyuki; Kojima, Shigeyuki; Hirayama, Keizo; Iwabuchi, Sadamu.

    1989-01-01

    Crossed cerebellar atrophy (CCA) was investigated by X-ray CT to establish the incidence, mechanism, and the relation to cerebral lesions in 130 cases of unilateral supratentorial cerebrovascular diseases. The 130 cases consisted of 83 males and 47 females with cerebral infarction (65 cases) and cerebral hemorrhage (65 cases). The patients' average age was 57.6 years. Crossed cerebellar atrophy was demonstrated in 8 cases (6.2%), 6 of whom had massive cerebral infarction in the middle cerebral artery area (9.2% of the 65 cases of cerebral infarction. The six cases of CCA caused by cerebral infarction had lesions in the frontal and temporal lobes. Two had a cerebral hemorrhage in the putamen and in the thalamus, respectively, accounting for 3.1% of the 65 cases of cerebral hemorrhage. Of the 2 cases, one had putaminal hemorrhage, and the other had thalamic hemorrhage. Cerebrovascular stroke had occured in these patients with CCA more than 2 months previously. In 5 of the 8 cases of CCA, atrophy was present in the basis pedunculi and the basis pontis on the side of the cerebral lesion. However, neither dilation nor deformity of the fourth ventricle was present in any of the patients, suggesting that none of the CCA patients had atrophy of the dentate nucleus. The CCA patients had massive cerebral lesion in the frontal and temporal lobes or atrophy of the basis pedunculi and basis pontis, suggesting the presence of the transsynaptic degeneration of the cortico-ponto-cerebellar pathway. In the case of the thalamic hemorrhage, who had not hemorrhagic lesion in the frontal and temporal lobes, atrophy of the basis peduncli and basis pontis was not observed. Though dilation or deformity of the fourth ventricle is not observed in this case, presence of the degeneration of the dentate-rubro-thalamic pathway cannot be denied. CCA seems to be caused by both the transsynaptic degeneration of the cortico-ponto-cerebellar pathway and the dentate-rubro-thalamic pathway. (J.P.N.)

  11. [Histological changes of gastric atrophy and intestinal metaplasia after Helicobacter pylori eradication].

    Science.gov (United States)

    Lee, Yonggu; Jeon, Yong Cheol; Koo, Tai Yeon; Cho, Hyun Seok; Byun, Tae Jun; Kim, Tae Yeob; Lee, Hang Lak; Eun, Chang Soo; Lee, Oh Young; Han, Dong Soo; Sohn, Joo Hyun; Yoon, Byung Chul

    2007-11-01

    Long-term Helicobater pylori infection results in atrophic gastritis and intestinal metaplasia, and increases the risk of gastric cancer. However, it is still controversial that eradication of H. pylori improves atrophy or metaplasia. Therefore, we investigated histological changes after the H. pylori eradication in patients with atrophy or metaplasia. One hundred seven patients who received successful eradication of H. pylori infection in Hanyang University, Guri Hospital from March 2001 to April 2006, were enrolled. Antral biopsy was taken before the eradication to confirm the H. pylori infection and grade of atrophy or metaplasia by updated Sydney System. After a certain period of time, antral biopsy was repeatedly taken to confirm the eradication and investigate histological changes of atrophy or metaplasia. Mean age of the patients was 55.3+/-11.3, and average follow-up period was 28.7+/-13.9 months. Endoscopic diagnosis included gastric ulcer, duodenal ulcer, non-ulcer antral gastritis. Atrophy was observed in 41 of 91 and their average score was 0.73+/-0.92. After the eradication of H. pylori, atrophy was improved (0.38+/-0.70, p=0.025). However, metaplasia which was observed in 49 of 107, did not significantly improve during the follow-up period. Newly developed atrophy (7 of 38) or metaplasia (18 of 49) was observed in patients who without atrophy or metaplasia initially. Their average scores were slightly lower than those of cases with pre-existing atrophy or metaplasia without statistical significance. After the eradication of H. pylori infection, atrophic gastritis may be improved, but change of intestinal metaplasia is milder and may take longer duration for improvement.

  12. Progressive cerebral atrophy in neuromyelitis optica.

    Science.gov (United States)

    Warabi, Yoko; Takahashi, Toshiyuki; Isozaki, Eiji

    2015-12-01

    We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients. © The Author(s), 2015.

  13. Analysis of voxel-based rCBF in patients with olivopontocerebellar atrophy of multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young Jin; Kang, Do Young; Park, Kyung Won; Kim, Sang Ho; Kim, Jae Woo [School of Medicine, Dong-A University, Busan (Korea, Republic of)

    2004-07-01

    Olivopontocerebellar Atrophy (OPCA) is one phenotype of multiple system atrophy (MSA) and is characterized neuropathologically by neuronal degeneration in the inferior olives, pons and cerebellar cortex. The diagnosis of OPCA requires clinical evaluation to exclude other diseases. And it's usually supported by atrophy of the cerebellum and brainstem visualized on CT or MRI. But there are some reports that the disease can occur without demonstrable atrophy in these anatomic studies. There are only a few reports about perfusion SPECT imaging in patients with OPCA. The aim of this study was to describe voxel-based rCBF of OPCA in comparison of healthy volunteers. We studied 5 patients with OPCA (1 men, 4 women: age 50.4{+-}9.6y) and age matched 13 healthy volunteers (4 men, 9 women: age 54.9{+-}6.6y). All subjects injected 20mCi of Tc-99m HMPAO and scanning was initiated 20 min after injection. Images were analyzed using SPM (SPM99) with Matlab 5.3. On visual analysis, in 3 patients with OPCA, SPECT image showed significant hypoperfusion in the cerebellum. In another 2 patients, diffuse hypoperfusion was found in the both cerebro-cerebellar hemispheres, untypical perfusion pattern in OPCA. So there is existed limitation to diagnosis by only visual analysis. On SPM analysis, in OPCA patients significantly decreased perfusion was present in culmen, tonsil, tuber in Lt. cerebellum and declive, tonsil, pyramid and inf. Semi-lunar lobule in Rt. cerebellum, Rt. inf. frontal gyrus and Rt. temporal lobe (p<0.001, uncorrected). We also performed individual analysis with SPM. Two of 5 patients have additional hypoperfusion brain lesions. In one patient, decreased perfusion found in Lt. temporal, both occipital lobe, Lt. parahippocampal gyrus. In another patient, decreased perfusion found in both frontal and parietal lobe. This study is one of a few trials analysis with SPM for OPCA. We defined the specific location of decreased perfusion in patients with OPCA.

  14. Analysis of voxel-based rCBF in patients with olivopontocerebellar atrophy of multiple system atrophy

    International Nuclear Information System (INIS)

    Jeong, Young Jin; Kang, Do Young; Park, Kyung Won; Kim, Sang Ho; Kim, Jae Woo

    2004-01-01

    Olivopontocerebellar Atrophy (OPCA) is one phenotype of multiple system atrophy (MSA) and is characterized neuropathologically by neuronal degeneration in the inferior olives, pons and cerebellar cortex. The diagnosis of OPCA requires clinical evaluation to exclude other diseases. And it's usually supported by atrophy of the cerebellum and brainstem visualized on CT or MRI. But there are some reports that the disease can occur without demonstrable atrophy in these anatomic studies. There are only a few reports about perfusion SPECT imaging in patients with OPCA. The aim of this study was to describe voxel-based rCBF of OPCA in comparison of healthy volunteers. We studied 5 patients with OPCA (1 men, 4 women: age 50.4±9.6y) and age matched 13 healthy volunteers (4 men, 9 women: age 54.9±6.6y). All subjects injected 20mCi of Tc-99m HMPAO and scanning was initiated 20 min after injection. Images were analyzed using SPM (SPM99) with Matlab 5.3. On visual analysis, in 3 patients with OPCA, SPECT image showed significant hypoperfusion in the cerebellum. In another 2 patients, diffuse hypoperfusion was found in the both cerebro-cerebellar hemispheres, untypical perfusion pattern in OPCA. So there is existed limitation to diagnosis by only visual analysis. On SPM analysis, in OPCA patients significantly decreased perfusion was present in culmen, tonsil, tuber in Lt. cerebellum and declive, tonsil, pyramid and inf. Semi-lunar lobule in Rt. cerebellum, Rt. inf. frontal gyrus and Rt. temporal lobe (p<0.001, uncorrected). We also performed individual analysis with SPM. Two of 5 patients have additional hypoperfusion brain lesions. In one patient, decreased perfusion found in Lt. temporal, both occipital lobe, Lt. parahippocampal gyrus. In another patient, decreased perfusion found in both frontal and parietal lobe. This study is one of a few trials analysis with SPM for OPCA. We defined the specific location of decreased perfusion in patients with OPCA

  15. A case of multiple system atrophy-parkinsonian type with stuttering- and palilalia-like dysfluencies and putaminal atrophy.

    Science.gov (United States)

    Kikuchi, Yoshikazu; Umezaki, Toshiro; Uehara, Taira; Yamaguchi, Hiroo; Yamashita, Koji; Hiwatashi, Akio; Sawatsubashi, Motohiro; Adachi, Kazuo; Yamaguchi, Yumi; Murakami, Daisuke; Kira, Jun-Ichi; Nakagawa, Takashi

    2017-11-14

    Both developmental and acquired stuttering are related to the function of the basal ganglia-thalamocortical loop, which includes the putamen. Here, we present a case of stuttering- and palilalia-like dysfluencies that manifested as an early symptom of multiple system atrophy-parkinsonian type (MSA-P) and bilateral atrophy of the putamen. The patient was a 72-year-old man with no history of developmental stuttering who presented with a stutter for consultation with our otorhinolaryngology department. The patient was diagnosed with MSA-P based on parkinsonism, autonomic dysfunction, and bilateral putaminal atrophy revealed by T2-weighted magnetic resonance imaging. Treatment with levodopa improved both the motor functional deficits related to MSA-P and stuttering-like dysfluencies while reading; however, the palilalia-like dysfluencies were much less responsive to levodopa therapy. The patient died of aspiration pneumonia two years after his first consultation at our hospital. In conclusion, adult-onset stuttering- and palilalia-like dysfluencies warrant careful examination of the basal ganglia-thalamocortical loop, and especially the putamen, using neuroimaging techniques. Acquired stuttering may be related to deficits in dopaminergic function. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Naltrexone treatment reverses astrocyte atrophy and immune dysfunction in self-harming macaques.

    Science.gov (United States)

    Lee, Kim M; Chiu, Kevin B; Didier, Peter J; Baker, Kate C; MacLean, Andrew G

    2015-11-01

    The role of glia in the development and treatment of behavioral abnormalities is understudied. Recent reports have observed glial activation in several disorders, including depression, autism spectrum disorders and self-injurious behaviors (SIB). In the current study, we examined SIB in the physiologically and anatomically relevant nonhuman primate (NHP) model. At the Tulane National Primate Research Center (TNPRC), approximately 5% of singly housed macaques develop symptoms of SIB. We have previously demonstrated that naltrexone hydrochloride can be effective in reducing SIB. We have also demonstrated that the astrocytes of animals with SIB are distinctly atrophic and display heightened innate immune activation compared with control animals. We have added a third group of animals (five macaques identified with SIB and treated with oral naltrexone at a dose of 3.2mg/kg) to the previous cohort (six macaques with a history of SIB but not treated, and nine animals with no history of SIB) for this study. Gray and white matter astrocytes from frontal cortical tissue were examined following necropsy. Innate immune activation of astrocytes, which was increased in SIB animals, was markedly decreased in animals receiving naltrexone, as was atrophy of both grey and white matter astrocytes. This was concomitant with improved behavioral correlates. Preventing astrocyte activation in select areas of the brain to reduce injurious behavior is an innovative concept with implications for mental health studies. Differences in multiple areas of primate brain would help determine how self-injurious behavior develops. These studies suggest a stronger role for astrocytes in the cellular events associated with self-injurious behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Interactions between entorhinal axons and target hippocampal neurons: a role for glutamate in the development of hippocampal circuitry.

    Science.gov (United States)

    Mattson, M P; Lee, R E; Adams, M E; Guthrie, P B; Kater, S B

    1988-11-01

    A coculture system consisting of input axons from entorhinal cortex explants and target hippocampal pyramidal neurons was used to demonstrate that glutamate, released spontaneously from afferent axons, can influence both dendritic geometry of target neurons and formation of presumptive synaptic sites. Dendritic outgrowth was reduced in hippocampal neurons growing on entorhinal axons when compared with neurons growing off the axons. Presumptive presynaptic sites were observed in association with hippocampal neuron dendrites and somas. HPLC analysis showed that glutamate was released from the explants in an activity- and Ca2(+)-dependent manner. The general glutamate receptor antagonist D-glutamylglycine significantly increased dendritic outgrowth in pyramidal neurons associated with entorhinal axons and reduced presumptive presynaptic sites. Tetrodotoxin and reduction of extracellular Ca2+ also promoted dendritic outgrowth and reduced the formation of presumptive synaptic sites. The results suggest that the neurotransmitter glutamate may play important roles in the development of hippocampal circuitry.

  18. Novel genetic loci associated with hippocampal volume

    NARCIS (Netherlands)

    D.P. Hibar (Derrek); H.H.H. Adams (Hieab); N. Jahanshad (Neda); G. Chauhan (Ganesh); J.L. Stein; E. Hofer (Edith); M.E. Rentería (Miguel); J.C. Bis (Joshua); A. Arias-Vásquez (Alejandro); Ikram, M.K. (M. Kamran); S. Desrivières (Sylvane); M.W. Vernooij (Meike); L. Abramovic (Lucija); S. Alhusaini (Saud); N. Amin (Najaf); M. Andersson (Micael); K. Arfanakis (Konstantinos); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); L. Athanasiu (Lavinia); T. Axelsson (Tomas); A.H. Beecham (Ashley); A. Beiser (Alexa); M. Bernard (Manon); S.H. Blanton (Susan H.); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.M. Brickman (Adam M.); Carmichael, O. (Owen); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); V. Chouraki (Vincent); G. Cuellar-Partida (Gabriel); F. Crivello (Fabrice); A. den Braber (Anouk); Doan, N.T. (Nhat Trung); S.M. Ehrlich (Stefan); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); R.F. Gottesman (Rebecca); O. Grimm (Oliver); M.D. Griswold (Michael); T. Guadalupe (Tulio); Gutman, B.A. (Boris A.); J. Hass (Johanna); U.K. Haukvik (Unn); D. Hoehn (David); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); Jørgensen, K.N. (Kjetil N.); N. Karbalai (Nazanin); D. Kasperaviciute (Dalia); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil); D.C. Liewald (David C.); L.M. Lopez (Lorna); M. Luciano (Michelle); C. MacAre (Christine); Marquand, A.F. (Andre F.); M. Matarin (Mar); R. Mather; M. Mattheisen (Manuel); McKay, D.R. (David R.); Milaneschi, Y. (Yuri); S. Muñoz Maniega (Susana); K. Nho (Kwangsik); A.C. Nugent (Allison); P. Nyquist (Paul); Loohuis, L.M.O. (Loes M. Olde); J. Oosterlaan (Jaap); M. Papmeyer (Martina); Pirpamer, L. (Lukas); B. Pütz (Benno); A. Ramasamy (Adaikalavan); Richards, J.S. (Jennifer S.); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); N. Rommelse (Nanda); S. Ropele (Stefan); E.J. Rose (Emma); N.A. Royle (Natalie); T. Rundek (Tatjana); P.G. Sämann (Philipp); Saremi, A. (Arvin); C.L. Satizabal (Claudia L.); L. Schmaal (Lianne); N.J. Schork (Nicholas); Shen, L. (Li); J. Shin (Jean); Shumskaya, E. (Elena); A.V. Smith (Albert Vernon); R. Sprooten (Roy); L.T. Strike (Lachlan); A. Teumer (Alexander); D. Tordesillas-Gutierrez (Diana); R. Toro (Roberto); D. Trabzuni (Danyah); S. Trompet (Stella); D. Vaidya (Dhananjay); J. van der Grond (Jeroen); S.J. van der Lee (Sven); Van Der Meer, D. (Dennis); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); T.G.M. van Erp (Theo G.); Van Rooij, D. (Daan); E. Walton (Esther); L.T. Westlye (Lars); C.D. Whelan (Christopher); B.G. Windham (B Gwen); A.M. Winkler (Anderson); K. Wittfeld (Katharina); G. Woldehawariat (Girma); A. Björnsson (Asgeir); Wolfers, T. (Thomas); L.R. Yanek (Lisa); Yang, J. (Jingyun); A.P. Zijdenbos; M.P. Zwiers (Marcel); I. Agartz (Ingrid); L. Almasy (Laura); D.J. Ames (David); Amouyel, P. (Philippe); O.A. Andreassen (Ole); S. Arepalli (Sampath); A.A. Assareh; S. Barral (Sandra); M.E. Bastin (Mark); Becker, D.M. (Diane M.); J.T. Becker (James); D.A. Bennett (David A.); J. Blangero (John); H. van Bokhoven (Hans); D.I. Boomsma (Dorret); H. Brodaty (Henry); R.M. Brouwer (Rachel); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan); K. Bulayeva (Kazima); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); D.M. Cannon (Dara); G. Cavalleri (Gianpiero); Cheng, C.-Y. (Ching-Yu); S. Cichon (Sven); M.R. Cookson (Mark); A. Corvin (Aiden); B. Crespo-Facorro (Benedicto); J.E. Curran (Joanne); M. Czisch (Michael); A.M. Dale (Anders); G.E. Davies (Gareth); A.J. de Craen (Anton); E.J.C. de Geus (Eco); P.L. de Jager (Philip); G.I. de Zubicaray (Greig); I.J. Deary (Ian J.); S. Debette (Stéphanie); C. DeCarli (Charles); N. Delanty; C. Depondt (Chantal); A.L. DeStefano (Anita); A. Dillman (Allissa); S. Djurovic (Srdjan); D.J. Donohoe (Dennis); D.A. Drevets (Douglas); Duggirala, R. (Ravi); M.D. Dyer (Matthew); C. Enzinger (Christian); S. Erk; T. Espeseth (Thomas); Fedko, I.O. (Iryna O.); Fernández, G. (Guillén); L. Ferrucci (Luigi); S.E. Fisher (Simon); D. Fleischman (Debra); I. Ford (Ian); M. Fornage (Myriam); T. Foroud (Tatiana); P.T. Fox (Peter); C. Francks (Clyde); Fukunaga, M. (Masaki); Gibbs, J.R. (J. Raphael); D.C. Glahn (David); R.L. Gollub (Randy); H.H.H. Göring (Harald H.); R.C. Green (Robert C.); O. Gruber (Oliver); V. Gudnason (Vilmundur); S. Guelfi (Sebastian); Håberg, A.K. (Asta K.); N.K. Hansell (Narelle); J. Hardy (John); C.A. Hartman (C.); Hashimoto, R. (Ryota); K. Hegenscheid (Katrin); J. Heinz (Judith); S. Le Hellard (Stephanie); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); Ho, B.-C. (Beng-Choon); P.J. Hoekstra (Pieter); W. Hoffmann (Wolfgang); A. Hofman (Albert); F. Holsboer (Florian); G. Homuth (Georg); N. Hosten (Norbert); J.J. Hottenga (Jouke Jan); M.J. Huentelman (Matthew); H.H. Pol; Ikeda, M. (Masashi); Jack, C.R. (Clifford R.); S. Jenkinson (Sarah); R. Johnson (Robert); Jönsson, E.G. (Erik G.); J.W. Jukema; R. Kahn (René); Kanai, R. (Ryota); I. Kloszewska (Iwona); Knopman, D.S. (David S.); P. Kochunov (Peter); Kwok, J.B. (John B.); S. Lawrie (Stephen); H. Lemaître (Herve); X. Liu (Xinmin); D.L. Longo (Dan L.); O.L. Lopez (Oscar L.); S. Lovestone (Simon); Martinez, O. (Oliver); J.-L. Martinot (Jean-Luc); V.S. Mattay (Venkata S.); McDonald, C. (Colm); A.M. McIntosh (Andrew); McMahon, F.J. (Francis J.); McMahon, K.L. (Katie L.); P. Mecocci (Patrizia); I. Melle (Ingrid); Meyer-Lindenberg, A. (Andreas); S. Mohnke (Sebastian); Montgomery, G.W. (Grant W.); D.W. Morris (Derek W); T.H. Mosley (Thomas H.); T.W. Mühleisen (Thomas); B. Müller-Myhsok (B.); M.A. Nalls (Michael); M. Nauck (Matthias); T.E. Nichols (Thomas); W.J. Niessen (Wiro); M.M. Nöthen (Markus); L. Nyberg (Lars); Ohi, K. (Kazutaka); R.L. Olvera (Rene); R.A. Ophoff (Roel); M. Pandolfo (Massimo); T. Paus (Tomas); Z. Pausova (Zdenka); B.W.J.H. Penninx (Brenda); Pike, G.B. (G. Bruce); S.G. Potkin (Steven); B.M. Psaty (Bruce); S. Reppermund; M. Rietschel (Marcella); J.L. Roffman (Joshua); N. Seiferth (Nina); J.I. Rotter (Jerome I.); M. Ryten (Mina); Sacco, R.L. (Ralph L.); P.S. Sachdev (Perminder); A.J. Saykin (Andrew); R. Schmidt (Reinhold); Schmidt, H. (Helena); C.J. Schofield (Christopher); Sigursson, S. (Sigurdur); Simmons, A. (Andrew); A. Singleton (Andrew); S.M. Sisodiya (Sanjay); Smith, C. (Colin); J.W. Smoller; H. Soininen (H.); V.M. Steen (Vidar); D.J. Stott (David J.); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); M. Tsolaki (Magda); C. Tzourio (Christophe); A.G. Uitterlinden (André); Hernández, M.C.V. (Maria C. Valdés); M.P. van der Brug (Marcel); A. van der Lugt (Aad); N.J. van der Wee (Nic); N.E.M. van Haren (Neeltje E.); D. van 't Ent (Dennis); M.J.D. van Tol (Marie-José); B.N. Vardarajan (Badri); B. Vellas (Bruno); D.J. Veltman (Dick); H. Völzke (Henry); H.J. Walter (Henrik); J. Wardlaw (Joanna); A.M.J. Wassink (Annemarie); M.E. Weale (Michael); Weinberger, D.R. (Daniel R.); Weiner, M.W. (Michael W.); Wen, W. (Wei); E. Westman (Eric); T.J.H. White (Tonya); Wong, T.Y. (Tien Y.); Wright, C.B. (Clinton B.); R.H. Zielke (Ronald H.); A.B. Zonderman; N.G. Martin (Nicholas); C.M. van Duijn (Cornelia); M.J. Wright (Margaret); W.T. Longstreth Jr; G. Schumann (Gunter); H.J. Grabe (Hans Jörgen); B. Franke (Barbara); L.J. Launer (Lenore); S.E. Medland (Sarah Elizabeth); S. Seshadri (Sudha); P.M. Thompson (Paul); M.K. Ikram (Kamran)

    2017-01-01

    textabstractThe hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic

  19. Orphan disease: Cherubism, optic atrophy, and short stature

    OpenAIRE

    Balaji Jeevanandham; Rajoo Ramachandran; Vignesh Dhanapal; Ilanchezhian Subramanian; Venkata Sai

    2018-01-01

    A 12-year-old female presented with complaints of progressive visual impairment in both her eyes. On clinical examination, she was short for her age and her ophthalmoscopic examination revealed bilateral optic atrophy. Computed tomography of the patient revealed multiple expansile lytic lesions of mandible suggesting cherubism. The optic atrophy was confirmed on magnetic resonance imaging, which additionally revealed bilateral retrocerebellar arachnoid cysts. This association of cherubism wit...

  20. Brain Injury-Induced Synaptic Reorganization in Hilar Inhibitory Neurons Is Differentially Suppressed by Rapamycin.

    Science.gov (United States)

    Butler, Corwin R; Boychuk, Jeffery A; Smith, Bret N

    2017-01-01

    Following traumatic brain injury (TBI), treatment with rapamycin suppresses mammalian (mechanistic) target of rapamycin (mTOR) activity and specific components of hippocampal synaptic reorganization associated with altered cortical excitability and seizure susceptibility. Reemergence of seizures after cessation of rapamycin treatment suggests, however, an incomplete suppression of epileptogenesis. Hilar inhibitory interneurons regulate dentate granule cell (DGC) activity, and de novo synaptic input from both DGCs and CA3 pyramidal cells after TBI increases their excitability but effects of rapamycin treatment on the injury-induced plasticity of interneurons is only partially described. Using transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed in the somatostatinergic subset of hilar inhibitory interneurons, we tested the effect of daily systemic rapamycin treatment (3 mg/kg) on the excitability of hilar inhibitory interneurons after controlled cortical impact (CCI)-induced focal brain injury. Rapamycin treatment reduced, but did not normalize, the injury-induced increase in excitability of surviving eGFP+ hilar interneurons. The injury-induced increase in response to selective glutamate photostimulation of DGCs was reduced to normal levels after mTOR inhibition, but the postinjury increase in synaptic excitation arising from CA3 pyramidal cell activity was unaffected by rapamycin treatment. The incomplete suppression of synaptic reorganization in inhibitory circuits after brain injury could contribute to hippocampal hyperexcitability and the eventual reemergence of the epileptogenic process upon cessation of mTOR inhibition. Further, the cell-selective effect of mTOR inhibition on synaptic reorganization after CCI suggests possible mechanisms by which rapamycin treatment modifies epileptogenesis in some models but not others.

  1. Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas

    2016-03-01

    Full Text Available ABSTRACT Multiple sclerosis (MS was always considered as a white matter inflammatory disease. Today, there is an important body of evidence that supports the hypothesis that gray matter involvement and the neurodegenerative mechanism are at least partially independent from inflammation. Gray matter atrophy develops faster than white matter atrophy, and predominates in the initial stages of the disease. The neurodegenerative mechanism creates permanent damage and correlates with physical and cognitive disability. In this review we describe the current available evidence regarding brain atrophy and its consequence in MS patients.

  2. Novel genetic loci associated with hippocampal volume

    NARCIS (Netherlands)

    Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivières, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S.; Armstrong, Nicola J.; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H.; Beiser, Alexa; Bernard, Manon; Blanton, Susan H.; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brickman, Adam M.; Carmichael, Owen; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L.; Gottesman, Rebecca F.; Grimm, Oliver; Griswold, Michael E.; Guadalupe, Tulio; Gutman, Boris A.; Hass, Johanna; Haukvik, Unn K.; Hoehn, David; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N.; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Liewald, David C. M.; Lopez, Lorna M.; Luciano, Michelle; Macare, Christine; Marquand, Andre F.; Matarin, Mar; Mather, Karen A.; Mattheisen, Manuel; McKay, David R.; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C.; Nyquist, Paul; Loohuis, Loes M. Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S.; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J.; Royle, Natalie A.; Rundek, Tatjana; Sämann, Philipp G.; Saremi, Arvin; Satizabal, Claudia L.; Schmaal, Lianne; Schork, Andrew J.; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V.; Sprooten, Emma; Strike, Lachlan T.; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; van der Grond, Jeroen; van der Lee, Sven J.; van der Meer, Dennis; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; van Erp, Theo G. M.; van Rooij, Daan; Walton, Esther; Westlye, Lars T.; Whelan, Christopher D.; Windham, Beverly G.; Winkler, Anderson M.; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R.; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P.; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A.; Arepalli, Sampath; Assareh, Amelia A.; Barral, Sandra; Bastin, Mark E.; Becker, Diane M.; Becker, James T.; Bennett, David A.; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I.; Brodaty, Henry; Brouwer, Rachel M.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cahn, Wiepke; Calhoun, Vince D.; Cannon, Dara M.; Cavalleri, Gianpiero L.; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R.; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E.; Czisch, Michael; Dale, Anders M.; Davies, Gareth E.; de Craen, Anton J. M.; de Geus, Eco J. C.; de Jager, Philip L.; de Zubicaray, Greig I.; Deary, Ian J.; Debette, Stéphanie; Decarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C.; Duggirala, Ravi; Dyer, Thomas D.; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O.; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E.; Fleischman, Debra A.; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M.; Fox, Peter T.; Francks, Clyde; Fukunaga, Masaki; Gibbs, J. Raphael; Glahn, David C.; Gollub, Randy L.; Göring, Harald H. H.; Green, Robert C.; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K.; Hansell, Narelle K.; Hardy, John; Hartman, Catharina A.; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G.; Heslenfeld, Dirk J.; Ho, Beng-Choon; Hoekstra, Pieter J.; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Pol, Hilleke E. Hulshoff; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G.; Jukema, J. Wouter; Kahn, René S.; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L.; Lopez, Oscar L.; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Francis J.; McMahon, Katie L.; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W.; Morris, Derek W.; Mosley, Thomas H.; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Nalls, Michael A.; Nauck, Matthias; Nichols, Thomas E.; Niessen, Wiro J.; Nöthen, Markus M.; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L.; Ophoff, Roel A.; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W. J. H.; Pike, G. Bruce; Potkin, Steven G.; Psaty, Bruce M.; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L.; Romanczuk-Seiferth, Nina; Rotter, Jerome I.; Ryten, Mina; Sacco, Ralph L.; Sachdev, Perminder S.; Saykin, Andrew J.; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R.; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M.; Smith, Colin; Smoller, Jordan W.; Soininen, Hilkka; Steen, Vidar M.; Stott, David J.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G.; Hernández, Maria C. Valdés; van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J. A.; van Haren, Neeltje E. M.; van 't Ent, Dennis; van Tol, Marie-Jose; Vardarajan, Badri N.; Vellas, Bruno; Veltman, Dick J.; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M.; Wassink, Thomas H.; Weale, Michael E.; Weinberger, Daniel R.; Weiner, Michael W.; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y.; Wright, Clinton B.; Zielke, Ronald H.; Zonderman, Alan B.; Martin, Nicholas G.; van Duijn, Cornelia M.; Wright, Margaret J.; Longstreth, W. T.; Schumann, Gunter; Grabe, Hans J.; Franke, Barbara; Launer, Lenore J.; Medland, Sarah E.; Seshadri, Sudha; Thompson, Paul M.; Ikram, M. Arfan

    2017-01-01

    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of

  3. Visual performance of pigeons following hippocampal lesions.

    Science.gov (United States)

    Bingman, V P; Hodos, W

    1992-11-15

    The effect of hippocampal lesions on performance in two psychophysical measures of spatial vision (acuity and size-difference threshold) was examined in 7 pigeons. No difference between the preoperative and postoperative thresholds of the experimental birds was found. The visual performance of pigeons in the psychophysical tasks failed to reveal a role of the hippocampal formation in vision. The results argue strongly that the behavioral deficits found in pigeons with hippocampal lesions when tested in a variety of memory-related spatial tasks is not based on a defect in spatial vision but impaired spatial cognition.

  4. Effects of early nerve repair on experimental brachial plexus injury in neonatal rats.

    Science.gov (United States)

    Bourke, Gráinne; McGrath, Aleksandra M; Wiberg, Mikael; Novikov, Lev N

    2018-03-01

    Obstetrical brachial plexus injury refers to injury observed at the time of delivery, which may lead to major functional impairment in the upper limb. In this study, the neuroprotective effect of early nerve repair following complete brachial plexus injury in neonatal rats was examined. Brachial plexus injury induced 90% loss of spinal motoneurons and 70% decrease in biceps muscle weight at 28 days after injury. Retrograde degeneration in spinal cord was associated with decreased density of dendritic branches and presynaptic boutons and increased density of astrocytes and macrophages/microglial cells. Early repair of the injured brachial plexus significantly delayed retrograde degeneration of spinal motoneurons and reduced the degree of macrophage/microglial reaction but had no effect on muscle atrophy. The results demonstrate that early nerve repair of neonatal brachial plexus injury could promote survival of injured motoneurons and attenuate neuroinflammation in spinal cord.

  5. Renal Atrophy Secondary to Chemoradiotherapy of Abdominal Malignancies

    International Nuclear Information System (INIS)

    Yang, Gary Y.; May, Kilian Salerno; Iyer, Renuka V.; Chandrasekhar, Rameela M.A.; Wilding, Gregory E.; McCloskey, Susan A.; Khushalani, Nikhil I.; Yendamuri, Saikrishna S.; Gibbs, John F.; Fakih, Marwan; Thomas, Charles R.

    2010-01-01

    Purpose: To identify factors predictive of renal atrophy after chemoradiotherapy of gastrointestinal malignancies. Methods and Materials: Patients who received chemotherapy and abdominal radiotherapy (RT) between 2002 and 2008 were identified for this study evaluating change in kidney size and function after RT. Imaging and biochemical data were obtained before and after RT in 6-month intervals. Kidney size was defined by craniocaudal measurement on CT images. The primarily irradiated kidney (PK) was defined as the kidney that received the greater mean kidney dose. Receiver operating characteristic (ROC) curves were generated to predict risk for renal atrophy. Results: Of 130 patients, median age was 64 years, and 51.5% were male. Most primary disease sites were pancreas and periampullary tumors (77.7%). Median follow-up was 9.4 months. Creatinine clearance declined 20.89%, and size of the PK decreased 4.67% 1 year after completion of chemoradiation. Compensatory hypertrophy of the non-PK was not seen. Percentage volumes of the PK receiving ≥10 Gy (V 10 ), 15 Gy (V 15 ), and 20 Gy (V 20 ) were significantly associated with renal atrophy 1 year after RT (p = 0.0030, 0.0029, and 0.0028, respectively). Areas under the ROC curves for V 10 , V 15 , and V 20 to predict >5% decrease in PK size were 0.760, 0.760, and 0.762, respectively. Conclusions: Significant detriments in PK size and renal function were seen after abdominal RT. The V 10 , V 15 , and V 20 were predictive of risk for PK atrophy 1 year after RT. Analyses suggest the association of lower-dose renal irradiation with subsequent development of renal atrophy.

  6. Hippocampal “Time Cells”: Time versus Path Integration

    Science.gov (United States)

    Kraus, Benjamin J.; Robinson, Robert J.; White, John A.; Eichenbaum, Howard; Hasselmo, Michael E.

    2014-01-01

    SUMMARY Recent studies have reported the existence of hippocampal “time cells,” neurons that fire at particular moments during periods when behavior and location are relatively constant. However, an alternative explanation of apparent time coding is that hippocampal neurons “path integrate” to encode the distance an animal has traveled. Here, we examined hippocampal neuronal firing patterns as rats ran in place on a treadmill, thus “clamping” behavior and location, while we varied the treadmill speed to distinguish time elapsed from distance traveled. Hippocampal neurons were strongly influenced by time and distance, and less so by minor variations in location. Furthermore, the activity of different neurons reflected integration over time and distance to varying extents, with most neurons strongly influenced by both factors and some significantly influenced by only time or distance. Thus, hippocampal neuronal networks captured both the organization of time and distance in a situation where these dimensions dominated an ongoing experience. PMID:23707613

  7. Hippocampal-neocortical functional reorganization underlies children's cognitive development.

    Science.gov (United States)

    Qin, Shaozheng; Cho, Soohyun; Chen, Tianwen; Rosenberg-Lee, Miriam; Geary, David C; Menon, Vinod

    2014-09-01

    The importance of the hippocampal system for rapid learning and memory is well recognized, but its contributions to a cardinal feature of children's cognitive development-the transition from procedure-based to memory-based problem-solving strategies-are unknown. Here we show that the hippocampal system is pivotal to this strategic transition. Longitudinal functional magnetic resonance imaging (fMRI) in 7-9-year-old children revealed that the transition from use of counting to memory-based retrieval parallels increased hippocampal and decreased prefrontal-parietal engagement during arithmetic problem solving. Longitudinal improvements in retrieval-strategy use were predicted by increased hippocampal-neocortical functional connectivity. Beyond childhood, retrieval-strategy use continued to improve through adolescence into adulthood and was associated with decreased activation but more stable interproblem representations in the hippocampus. Our findings provide insights into the dynamic role of the hippocampus in the maturation of memory-based problem solving and establish a critical link between hippocampal-neocortical reorganization and children's cognitive development.

  8. Ataxia-telangiectasia: the pattern of cerebellar atrophy on MRI

    International Nuclear Information System (INIS)

    Tavani, F.; Zimmerman, R.A.; Gatti, R.; Bingham, P.; Berry, G.T.; Sullivan, K.

    2003-01-01

    We describe MRI of the brain in 19 patients with ataxia-telangiectasia (AT) and correlate the appearances with the degree of neurologic deficit. We examined 10 male and nine female patients; 17 were aged between 2 and 12 years (mean 8 years) but a woman and her brother were 35 and 38 years old, and had a variant of AT. Ataxia was the first recognized sign of the disease in every patient. We detected the following patterns of cerebellar atrophy: in the youngest patient, aged 2 years, the study was normal; in the five next youngest patients 3-7 years of age, the lateral cerebellum and superior vermis showed the earliest changes of atrophy; and all but one of the other patients had moderate to marked diffuse atrophy of vermis and cerebellar hemispheres. There were 12 patients aged 9 years and above; one, who was normal, was 9 years old. The five patients who at the time of examination were unable to walk all had diffuse atrophy involving both vermis and cerebellar hemispheres. (orig.)

  9. Influence of mild traumatic brain injury during pediatric stage on short-term memory and hippocampal apoptosis in adult rats.

    Science.gov (United States)

    Park, Mi-Sook; Oh, Hyean-Ae; Ko, Il-Gyu; Kim, Sung-Eun; Kim, Sang-Hoon; Kim, Chang-Ju; Kim, Hyun-Bae; Kim, Hong

    2014-06-01

    Traumatic brain injury (TBI) is a leading cause of neurological deficit in the brain, which induces short- and long-term brain damage, cognitive impairment with/without structural alteration, motor deficits, emotional problems, and death both in children and adults. In the present study, we evaluated whether mild TBI in childhood causes persisting memory impairment until adulthood. Moreover, we investigated the influence of mild TBI on memory impairment in relation with hippocampal apoptosis. For this, step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and immunohistochemistry for caspase-3 were performed. Male Sprague-Dawley rats were used in the experiments. The animals were randomly divided into two groups: sham-operation group and TBI-induction group. The mild TBI model was created with an electromagnetic contusion device activated at a velocity of 3.0 m/sec. The results showed that mild TBI during the pediatric stage significantly decreased memory retention. The numbers of TUNEL-positive and caspase-3-positive cells were increased in the TBI-induction group compared to those in the sham-operation group. Defective memory retention and apoptosis sustained up to the adult stage. The present results shows that mild TBI induces long-lasting cognitive impairment from pediatric to adult stages in rats through the high level of apoptosis. The finding of this study suggests that children with mild TBI may need intensive treatments for the reduction of long-lasting cognitive impairment by secondary neuronal damage.

  10. Pathway-focused PCR array profiling of enriched populations of laser capture microdissected hippocampal cells after traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Deborah R Boone

    Full Text Available Cognitive deficits in survivors of traumatic brain injury (TBI are associated with irreversible neurodegeneration in brain regions such as the hippocampus. Comparative gene expression analysis of dying and surviving neurons could provide insight into potential therapeutic targets. We used two pathway-specific PCR arrays (RT2 Profiler Apoptosis and Neurotrophins & Receptors PCR arrays to identify and validate TBI-induced gene expression in dying (Fluoro-Jade-positive or surviving (Fluoro-Jade-negative pyramidal neurons obtained by laser capture microdissection (LCM. In the Apoptosis PCR array, dying neurons showed significant increases in expression of genes associated with cell death, inflammation, and endoplasmic reticulum (ER stress compared with adjacent, surviving neurons. Pro-survival genes with pleiotropic functions were also significantly increased in dying neurons compared to surviving neurons, suggesting that even irreversibly injured neurons are able to mount a protective response. In the Neurotrophins & Receptors PCR array, which consists of genes that are normally expected to be expressed in both groups of hippocampal neurons, only a few genes were expressed at significantly different levels between dying and surviving neurons. Immunohistochemical analysis of selected, differentially expressed proteins supported the gene expression data. This is the first demonstration of pathway-focused PCR array profiling of identified populations of dying and surviving neurons in the brain after TBI. Combining precise laser microdissection of identifiable cells with pathway-focused PCR array analysis is a practical, low-cost alternative to microarrays that provided insight into neuroprotective signals that could be therapeutically targeted to ameliorate TBI-induced neurodegeneration.

  11. Tensor-Based Morphometry Reveals Volumetric Deficits in Moderate=Severe Pediatric Traumatic Brain Injury

    Science.gov (United States)

    Hua, Xue; Villalon-Reina, Julio; Moran, Lisa M.; Kernan, Claudia; Babikian, Talin; Mink, Richard; Babbitt, Christopher; Johnson, Jeffrey; Giza, Christopher C.; Thompson, Paul M.; Asarnow, Robert F.

    2016-01-01

    Abstract Traumatic brain injury (TBI) can cause widespread and prolonged brain degeneration. TBI can affect cognitive function and brain integrity for many years after injury, often with lasting effects in children, whose brains are still immature. Although TBI varies in how it affects different individuals, image analysis methods such as tensor-based morphometry (TBM) can reveal common areas of brain atrophy on magnetic resonance imaging (MRI), secondary effects of the initial injury, which will differ between subjects. Here we studied 36 pediatric moderate to severe TBI (msTBI) participants in the post-acute phase (1–6 months post-injury) and 18 msTBI participants who returned for their chronic assessment, along with well-matched controls at both time-points. Participants completed a battery of cognitive tests that we used to create a global cognitive performance score. Using TBM, we created three-dimensional (3D) maps of individual and group differences in regional brain volumes. At both the post-acute and chronic time-points, the greatest group differences were expansion of the lateral ventricles and reduction of the lingual gyrus in the TBI group. We found a number of smaller clusters of volume reduction in the cingulate gyrus, thalamus, and fusiform gyrus, and throughout the frontal, temporal, and parietal cortices. Additionally, we found extensive associations between our cognitive performance measure and regional brain volume. Our results indicate a pattern of atrophy still detectable 1-year post-injury, which may partially underlie the cognitive deficits frequently found in TBI. PMID:26393494

  12. Hippocampal lesions, contextual retrieval, and autoshaping in pigeons.

    Science.gov (United States)

    Richmond, Jenny; Colombo, Michael

    2002-02-22

    Both pigeons and rats with damage to the hippocampus are slow to acquire an autoshaped response and emit fewer overall responses than control animals. Experiment 1 explored the possibility that the autoshaping deficit was due to an impairment in contextual retrieval. Pigeons were trained for 14 days on an autoshaping task in which a red stimulus was followed by reinforcement in context A, and a green stimulus was followed by reinforcement in context B. On day 15, the subjects were given a context test in which the red and green stimuli were presented simultaneously in context A and then later in context B. Both control and hippocampal animals showed context specificity, that is, they responded more to the red stimulus in context A and to the green stimulus in context B. In Experiment 2 we video-recorded the control and hippocampal animals performing the autoshaping task. Hippocampal animals tended to miss-peck the key more often than control animals. In addition, the number of missed pecks increased across days for hippocampal animals but not for control animals, suggesting that while the control animals increased their pecking accuracy, the hippocampal animals actually decreased their pecking accuracy. Our findings suggest that impairments in moving through space may underlie the hippocampal autoshaping deficit.

  13. Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems.

    Science.gov (United States)

    Komatsu, Riyo; Okazaki, Tatsuma; Ebihara, Satoru; Kobayashi, Makoto; Tsukita, Yoko; Nihei, Mayumi; Sugiura, Hisatoshi; Niu, Kaijun; Ebihara, Takae; Ichinose, Masakazu

    2018-05-22

    Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase-3, followed by further degradation by the ubiquitin-proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle. For swallowing muscles, it is not clear whether they produce cytokines. The main objective of this study was to determine whether aspiration pneumonia induces muscle atrophy in the respiratory (the diaphragm), skeletal (the tibialis anterior, TA), and swallowing (the tongue) systems, and their possible mechanisms. We employed a mouse aspiration pneumonia model and computed tomography (CT) scans of aged pneumonia patients. To induce aspiration pneumonia, mice were inoculated with low dose pepsin and lipopolysaccharide solution intra-nasally 5 days a week. The diaphragm, TA, and tongue were isolated, and total RNA, proteins, and frozen sections were stored. Quantitative real-time polymerase chain reaction determined the expression levels of proinflammatory cytokines, muscle E3 ubiquitin ligases, and autophagy related genes. Western blot analysis determined the activation of the muscle proteolysis pathway. Frozen sections determined the presence of muscle atrophy. CT scans were used to evaluate the muscle atrophy in aged aspiration pneumonia patients. The aspiration challenge enhanced the expression levels of proinflammatory cytokines in the diaphragm, TA, and tongue. Among muscle proteolysis pathways, the aspiration challenge activated caspase-3 in all the three muscles examined, whereas calpains were activated in the diaphragm and the TA but not in the tongue. Activation of the ubiquitin-proteasome system was detected in all the three muscles examined. The aspiration challenge

  14. Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults.

    Science.gov (United States)

    Maass, Anne; Düzel, Sandra; Brigadski, Tanja; Goerke, Monique; Becke, Andreas; Sobieray, Uwe; Neumann, Katja; Lövdén, Martin; Lindenberger, Ulman; Bäckman, Lars; Braun-Dullaeus, Rüdiger; Ahrens, Dörte; Heinze, Hans-Jochen; Müller, Notger G; Lessmann, Volkmar; Sendtner, Michael; Düzel, Emrah

    2016-05-01

    Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here. Copyright © 2015 The Authors

  15. Modulators of cytoskeletal reorganization in CA1 hippocampal neurons show increased expression in patients at mid-stage Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Patricia F Kao

    2010-10-01

    Full Text Available During the progression of Alzheimer's disease (AD, hippocampal neurons undergo cytoskeletal reorganization, resulting in degenerative as well as regenerative changes. As neurofibrillary tangles form and dystrophic neurites appear, sprouting neuronal processes with growth cones emerge. Actin and tubulin are indispensable for normal neurite development and regenerative responses to injury and neurodegenerative stimuli. We have previously shown that actin capping protein beta2 subunit, Capzb2, binds tubulin and, in the presence of tau, affects microtubule polymerization necessary for neurite outgrowth and normal growth cone morphology. Accordingly, Capzb2 silencing in hippocampal neurons resulted in short, dystrophic neurites, seen in neurodegenerative diseases including AD. Here we demonstrate the statistically significant increase in the Capzb2 expression in the postmortem hippocampi in persons at mid-stage, Braak and Braak stage (BB III-IV, non-familial AD in comparison to controls. The dynamics of Capzb2 expression in progressive AD stages cannot be attributed to reactive astrocytosis. Moreover, the increased expression of Capzb2 mRNA in CA1 pyramidal neurons in AD BB III-IV is accompanied by an increased mRNA expression of brain derived neurotrophic factor (BDNF receptor tyrosine kinase B (TrkB, mediator of synaptic plasticity in hippocampal neurons. Thus, the up-regulation of Capzb2 and TrkB may reflect cytoskeletal reorganization and/or regenerative response occurring in hippocampal CA1 neurons at a specific stage of AD progression.

  16. Detection of brain atrophy due to ACTH or corticosteroid therapy with computed tomography

    International Nuclear Information System (INIS)

    Tamai, Isamu; Takei, Tadao; Oota, Hideomi; Maekawa, Kihei.

    1981-01-01

    Adrenocorticotropic hormone (ACTH) or corticosteroids seemed to cause brain atrophy in intants. We studied the atrophy which was caused by these drugs with computed tomography (CT). 1) Nine cases of infantile spasms examined before, during and after ACTH therepy with CT. Brain atrophy on CT was observed immediately after the completion of ACTH therapy. The brain atrophy receded slightly after several months. It was more marked in younger patients, in cases treated by hight doses of ACTH and in cases where brain atrophy had already been obserbed before ACTH therapy. 2) Twenty cases of infantile spasms or Lennox Gastaut syndrome were examined after ACTH therapy with CT. Brain atrophy was observed in twelve cases. Main features of brain atrophy were the enlargement of sylvian fissure and the widening of subarachnoid space at the frontal or temporal region. Mental retardation was observed in eighteen cases. 3) Two cases of nephrotic syndrome were treated with pulse therapy of prednisolone. CT was carried out before and after treatment. Atrophy of cerebrum was observed in these cases. 4) A case of infantile spasms treated with anticonvulsants without ACTH was studied by electroencephalography (EEG) and CT. The abnormal pattern of EEG was markedly corrected, while brain atrophy on CT was not observed after the therapy. Because of these observations the use of ACTH has to be reconsidered. ACTH should be the drug of second choice for the therapy of infantile spasms and should be used in case other anticonvulsants have no effect. ACTH should be used at lower dosages and for shorter periods of time. (author)

  17. Detection of brain atrophy due to ACTH or corticosteroid therapy with computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Tamai, I.; Takei, T. (National Sagamihara Hospital, Kanagawa (Japan)); Oota, H.; Maekawa, K.

    1981-07-01

    Adrenocorticotropic hormone (ACTH) or corticosteroids seemed to cause brain atrophy in infants. We studied the atrophy which was caused by these drugs with computed tomography (CT). 1) Nine cases of infantile spasms examined before, during and after ACTH therapy with CT. Brain atrophy on CT was observed immediately after the completion of ACTH therapy. The brain atrophy receded slightly after several months. It was more marked in younger patients, in cases treated by high doses of ACTH and in cases where brain atrophy had already been observed before ACTH therapy. 2) Twenty cases of infantile spasms or Lennox Gastaut syndrome were examined after ACTH therapy with CT. Brain atrophy was observed in twelve cases. Main features of brain atrophy were the enlargement of sylvian fissure and the widening of subarachnoid space at the frontal or temporal region. Mental retardation was observed in eighteen cases. 3) Two cases of nephrotic syndrome were treated with pulse therapy of prednisolone. CT was carried out before and after treatment. Atrophy of cerebrum was observed in these cases. 4) A case of infantile spasms treated with anticonvulsants without ACTH was studied by electroencephalography (EEG) and CT. The abnormal pattern of EEG was markedly corrected, while brain atrophy on CT was not observed after the therapy. Because of these observations the use of ACTH has to be reconsidered. ACTH should be the drug of second choice for the therapy of infantile spasms and should be used in case other anticonvulsants have no effect. ACTH should be used at lower dosages and for shorter periods of time.

  18. Preliminary study on computer automatic quantification of brain atrophy

    International Nuclear Information System (INIS)

    Li Chuanfu; Zhou Kangyuan

    2006-01-01

    Objective: To study the variability of normal brain volume with the sex and age, and put forward an objective standard for computer automatic quantification of brain atrophy. Methods: The cranial volume, brain volume and brain parenchymal fraction (BPF) of 487 cases of brain atrophy (310 males, 177 females) and 1901 cases of normal subjects (993 males, 908 females) were calculated with the newly developed algorithm of automatic quantification for brain atrophy. With the technique of polynomial curve fitting, the mathematical relationship of BPF with age in normal subjects was analyzed. Results: The cranial volume, brain volume and BPF of normal subjects were (1 271 322 ± 128 699) mm 3 , (1 211 725 ± 122 077) mm 3 and (95.3471 ± 2.3453)%, respectively, and those of atrophy subjects were (1 276 900 ± 125 180) mm 3 , (1 203 400 ± 117 760) mm 3 and BPF(91.8115 ± 2.3035)% respectively. The difference of BPF between the two groups was extremely significant (P 0.05). The expression P(x)=-0.0008x 2 + 0.0193x + 96.9999 could accurately describe the mathematical relationship between BPF and age in normal subject (lower limit of 95% CI y=-0.0008x 2 +0.0184x+95.1090). Conclusion: The lower limit of 95% confidence interval mathematical relationship between BPF and age could be used as an objective criteria for automatic quantification of brain atrophy with computer. (authors)

  19. Liver atrophy after percutaneous transhepatic portal embolization occurs in two histological phases: Hepatocellular atrophy followed by apoptosis.

    Science.gov (United States)

    Iwao, Yasuhito; Ojima, Hidenori; Kobayashi, Tatsushi; Kishi, Yoji; Nara, Satoshi; Esaki, Minoru; Shimada, Kazuaki; Hiraoka, Nobuyoshi; Tanabe, Minoru; Kanai, Yae

    2017-11-18

    To clarify the histological changes associated with liver atrophy after percutaneous transhepatic portal embolization (PTPE) in pigs and humans. As a preliminary study, we performed pathological examinations of liver specimens from five pigs that had undergone PTPE in a time-dependent model of liver atrophy. In specimens from embolized lobes (EMB) and nonembolized lobes (controls), we measured the portal vein to central vein distance (PV-CV), the area and number of hepatocytes per lobule, and apoptotic activity using the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Immunohistochemical reactivities were evaluated for light chain 3 (LC3) and lysosomal-associated membrane protein 2 (LAMP2) as autophagy markers and for glutamine synthetase and cytochrome P450 2E1 (CYP2E1) as metabolic zonation markers. Samples from ten human livers taken 20-36 d after PTPE were similarly examined. PV-CVs and lobule areas did not differ between EMB and controls at day 0, but were lower in EMB than in controls at weeks 2, 4, and 6 ( P ≤ 0.001). Hepatocyte numbers were not significantly reduced in EMB at day 0 and week 2 but were reduced at weeks 4 and 6 ( P ≤ 0.05). Apoptotic activity was higher in EMB than in controls at day 0 and week 4. LC3 and LAMP2 staining peaked in EMB at week 2, with no significant difference between EMB and controls at weeks 4 and 6. Glutamine synthetase and CYP2E1 zonation in EMB at weeks 2, 4, and 6 were narrower than those in controls. Human results were consistent with those of porcine specimens. The mechanism of liver atrophy after PTPE has two histological phases: Hepatocellular atrophy is likely caused by autophagy in the first 2 wk and apoptosis thereafter.

  20. Characteristic MRI findings in multiple system atrophy: comparison of the three subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Naka, H.; Ohshita, T.; Murata, Y.; Imon, Y.; Mimori, Y.; Nakamura, S. [Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima (Japan)

    2002-03-01

    We reviewed MRI findings in 29 patients with probable multiple system atrophy (MSA) to see whether there were common and or less common neuroradiological findings in the various clinical subtypes. We divided the patients into three clinical subtypes according to initial and predominant symptoms: 14 with olivopontocerebellar atrophy (OPCA), eight with the Shy-Drager syndrome (SDS) and seven with striatonigral degeneration (SND). The patients showed atrophy of the brain stem and cerebellum, high signal on T2-weighted images of the base of the pons and middle cerebellar peduncles, high and low signal on T2-weighted images of the putamen and atrophy of frontal and parietal lobes. The degree of atrophy of the middle cerebellar peduncle and cerebellum was greater in OPCA patients and a high-signal lateral rim to the putamen more frequent in SND. However, all findings were observed in all subtypes, and the degrees of atrophy of the putamen and pons and the frequency of high signal in the base of the pons were similar in the subtypes. We also found atrophy of the cerebral hemispheres, especially the frontal and parietal lobes, but its degree was not significantly different in the various subtypes. Our findings suggest that, although MSA can be divided clinically into three subtypes, most of the features on MRI are common and overlap in the subtypes, independently of the clinical presentation. (orig.)

  1. Role of adult hippocampal neurogenesis in stress resilience

    Directory of Open Access Journals (Sweden)

    Brunno R. Levone

    2015-01-01

    Full Text Available There is a growing appreciation that adult hippocampal neurogenesis plays a role in emotional and cognitive processes related to psychiatric disorders. Although many studies have investigated the effects of stress on adult hippocampal neurogenesis, most have not focused on whether stress-induced changes in neurogenesis occur specifically in animals that are more resilient or more susceptible to the behavioural and neuroendocrine effects of stress. Thus, in the present review we explore whether there is a clear relationship between stress-induced changes in adult hippocampal neurogenesis, stress resilience and antidepressant-induced recovery from stress-induced changes in behaviour. Exposure to different stressors is known to reduce adult hippocampal neurogenesis, but some stressors have also been shown to exert opposite effects. Ablation of neurogenesis does not lead to a depressive phenotype, but it can enhance responsiveness to stress and affect stress susceptibility. Monoaminergic-targeted antidepressants, environmental enrichment and adrenalectomy are beneficial for reversing stress-induced changes in behaviour and have been shown to do so in a neurogenesis-dependant manner. In addition, stress and antidepressants can affect hippocampal neurogenesis, preferentially in the ventral hippocampus. Together, these data show that adult hippocampal neurogenesis may play a role in the neuroendocrine and behavioural responses to stress, although it is not yet fully clear under which circumstances neurogenesis promotes resilience or susceptibility to stress. It will be important that future studies carefully examine how adult hippocampal neurogenesis can contribute to stress resilience/susceptibility so that it may be appropriately exploited for the development of new and more effective treatments for stress-related psychiatric disorders.

  2. Egocentric and allocentric visuospatial working memory in premotor Huntington's disease: A double dissociation with caudate and hippocampal volumes.

    Science.gov (United States)

    Possin, Katherine L; Kim, Hosung; Geschwind, Michael D; Moskowitz, Tacie; Johnson, Erica T; Sha, Sharon J; Apple, Alexandra; Xu, Duan; Miller, Bruce L; Finkbeiner, Steven; Hess, Christopher P; Kramer, Joel H

    2017-07-01

    Our brains represent spatial information in egocentric (self-based) or allocentric (landmark-based) coordinates. Rodent studies have demonstrated a critical role for the caudate in egocentric navigation and the hippocampus in allocentric navigation. We administered tests of egocentric and allocentric working memory to individuals with premotor Huntington's disease (pmHD), which is associated with early caudate nucleus atrophy, and controls. Each test had 80 trials during which subjects were asked to remember 2 locations over 1-sec delays. The only difference between these otherwise identical tests was that locations could only be coded in self-based or landmark-based coordinates. We applied a multiatlas-based segmentation algorithm and computed point-wise Jacobian determinants to measure regional variations in caudate and hippocampal volumes from 3T MRI. As predicted, the pmHD patients were significantly more impaired on egocentric working memory. Only egocentric accuracy correlated with caudate volumes, specifically the dorsolateral caudate head, right more than left, a region that receives dense efferents from dorsolateral prefrontal cortex. In contrast, only allocentric accuracy correlated with hippocampal volumes, specifically intermediate and posterior regions that connect strongly with parahippocampal and posterior parietal cortices. These results indicate that the distinction between egocentric and allocentric navigation applies to working memory. The dorsolateral caudate is important for egocentric working memory, which can explain the disproportionate impairment in pmHD. Allocentric working memory, in contrast, relies on the hippocampus and is relatively spared in pmHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Lenaers Guy

    2012-07-01

    Full Text Available Abstract Definition of the disease Dominant Optic Atrophy (DOA is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology Two genes (OPA1, OPA3 encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8 are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7 are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Diagnosis Patients are usually diagnosed during their early childhood, because of

  4. The yearly rate of Relative Thalamic Atrophy (yrRTA: a simple 2D/3D method for estimating deep gray matter atrophy in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Manuel eMenéndez-González

    2014-08-01

    Full Text Available Despite a strong correlation to outcome, the measurement of gray matter (GM atrophy is not being used in daily clinical practice as a prognostic factor and monitor the effect of treatments in Multiple Sclerosis (MS. This is mainly because the volumetric methods available to date are sophisticated and difficult to implement for routine use in most hospitals. In addition, the meaning of raw results from volumetric studies on regions of interest are not always easy to understand. Thus, there is a huge need of a methodology suitable to be applied in daily clinical practice in order to estimate GM atrophy in a convenient and comprehensive way. Given the thalamus is the brain structure found to be more consistently implied in MS both in terms of extent of atrophy and in terms of prognostic value, we propose a solution based in this structure. In particular, we propose to compare the extent of thalamus atrophy (TA with the extent of unspecific, global brain atrophy, represented by ventricular enlargement. We name this ratio the yearly rate of Relative Thalamic Atrophy (yrRTA. In this report we aim to describe the concept of yrRTA and the guidelines for computing it under 2D and 3D approaches and explain the rationale behind this method. We have also conducted a very short crossectional retrospective study to proof the concept of yrRTA. However, we do not seek to describe here the validity of this parameter since these researches are being conducted currently and results will be addressed in future publications.

  5. The yearly rate of Relative Thalamic Atrophy (yrRTA): a simple 2D/3D method for estimating deep gray matter atrophy in Multiple Sclerosis.

    Science.gov (United States)

    Menéndez-González, Manuel; Salas-Pacheco, José M; Arias-Carrión, Oscar

    2014-01-01

    Despite a strong correlation to outcome, the measurement of gray matter (GM) atrophy is not being used in daily clinical practice as a prognostic factor and monitor the effect of treatments in Multiple Sclerosis (MS). This is mainly because the volumetric methods available to date are sophisticated and difficult to implement for routine use in most hospitals. In addition, the meanings of raw results from volumetric studies on regions of interest are not always easy to understand. Thus, there is a huge need of a methodology suitable to be applied in daily clinical practice in order to estimate GM atrophy in a convenient and comprehensive way. Given the thalamus is the brain structure found to be more consistently implied in MS both in terms of extent of atrophy and in terms of prognostic value, we propose a solution based in this structure. In particular, we propose to compare the extent of thalamus atrophy with the extent of unspecific, global brain atrophy, represented by ventricular enlargement. We name this ratio the "yearly rate of Relative Thalamic Atrophy" (yrRTA). In this report we aim to describe the concept of yrRTA and the guidelines for computing it under 2D and 3D approaches and explain the rationale behind this method. We have also conducted a very short crossectional retrospective study to proof the concept of yrRTA. However, we do not seek to describe here the validity of this parameter since these researches are being conducted currently and results will be addressed in future publications.

  6. Effects of Exercise Following Lateral Fluid Percussion Brain Injury in Rats.

    Science.gov (United States)

    Hicks, Ramona R.; Boggs, Arden; Leider, Denise; Kraemer, Philip; Brown, Russell; Scheff, Stephen W.; Seroogy, Kim B.

    1998-01-01

    Previous studies have suggested that brain-derived neurotrophic factor (BDNF) is involved in memory and learning, and may be neuroprotective following various brain insults. Exercise has been found to increase BDNF mRNA levels in various brain regions, including specific subpopulations of hippocampal neurons. In the present study, we were interested in whether following traumatic brain injury, exercise could increase BDNF mRNA expression, attenuate neuropathology, and improve cognitive and neuromoter performance. We subjected adult male Sprague-Dawley rats to a fluid percussion brain injury, followed by either 18 days of treadmill exercise or handling. Spatial memory was evaluated in a Morris Water Maze (MWM) and motor function was evaluated with a battery of neuromotor tests. Neuropathology was evaluated by measuring the cortical lesion volume and the extent of neuronal loss in the hipocampus. Expression of BDNF mRNA in the hippocampus was assessed with in situ hybridization and densitometry. Hybridization signal for BDNF mRNA was significantly increased bilaterally in the exercise group in hippocampal regions CA1 and CA3 (p<0.05), but not in the granule cell layer of the dentate gyrus. No significant differences were observed between the groups in neuropathology, spatial memory, or motor performance. This study suggests that after traumatic brain injury, exercise elevates BDNF mRNA in specific regions of the hippocampus.

  7. Diffusion MRI and the Detection of Alterations Following Traumatic Brain Injury

    Science.gov (United States)

    2017-06-13

    vascular injury, disruption of water home- ostasis), changes in tissue composition (e.g., increased or decreased cellu- larity), and alterations in...related alterations Tissue environment Expected diffusion changes Major citations dMRI evidence Neurons cell loss necrosis and apoptosis atrophy...structure and signaling, vascular coupling, and waste removal, among others. Astrocytes are at least as numerous as neurons in the brain (Herculano-Houzel

  8. Magnetic resonance volumetry of the hippocampus in familial spontaneous epileptic cats.

    Science.gov (United States)

    Mizoguchi, Shunta; Hasegawa, Daisuke; Kuwabara, Takayuki; Hamamoto, Yuji; Ogawa, Fukie; Fujiwara, Aki; Matsuki, Naoaki; Fujita, Michio

    2014-12-01

    A strain of familial spontaneous epileptic cats (FSECs) with typical limbic seizures was identified in 2010. The electroencephalographic features suggested that an epileptogenic zone is present in the mesial temporal structures (i.e., amygdala and/or hippocampus). In this study, visual evaluations and quantitative analyses were performed by using 3D MR hippocampal volumetry in comparing FSECs with age-matched controls. Visual hippocampal asymmetries were seen in 8 of 14 (57.1%) FSECs. The FSEC group showed a significantly higher asymmetric ratio (4.15%) than the control group (0.99%). The smaller side of hippocampal volume (HV) (0.206 cm(3)) in FSECs was significantly smaller than the mean HV in controls (0.227 cm(3)). However, the means of left and right HVs and total HVs in FSECs showed no differences because the laterality of hippocampal atrophy was different in each individual. Therefore, since FSECs represent a true model of spontaneous epilepsy, hippocampal volumetry should be evaluated in each individual as well as in human patients. The significant asymmetry of HV suggests the potential for hippocampal atrophy in FSECs. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Corpus callosum atrophy in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Frederiksen, Kristian Steen; Garde, Ellen; Skimminge, Arnold

    2011-01-01

    Several studies have found atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD). However, it remains unclear whether callosal atrophy is already present in the early stages of AD, and to what extent it may be associated with other structural changes in the brain......, such as age-related white matter changes (ARWMC) and progression of the disease....

  10. Clinical and MRI correlation in multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Negoro, Kiyoshi; Morimatsu, Mitsunori (Yamaguchi Univ., Ube (Japan). School of Medicine)

    1994-05-01

    By using magnetic resonance imaging (MRI), we studied 11 patients with multiple system atrophy (MSA): 5 olivo-pontocerebellar atrophy (OPCA), 2 Shy-Drager syndrome (SDS), and 4 striatonigral degeneration (SND). The diagnoses of OPCA, SDS and SND were clinically made. The MR images were performed on 1.5 tesla MRI unit (Siemens Asahi Medical, Magnetom H15), using a T[sub 2]-weighted spin echo (SE) sequence (TR: 2000-3000 ms, TE: 80-90 ms), a T[sub 1]-weighted SE sequence (TR: 550, TE: 15), and a proton density-weighted (PD) SE sequence (TR: 2000-3000, TE: 12-22). In the patients with OPCA, MRI revealed cerebellar and brainstem atrophy and degeneration of pontine transverse fibers more marked than in the patients with SDS and SND. T[sub 2]-weighted images showed low intensity in posterolateral putamina in one OPCA patient and all of SDS and SND patients. PD images demonstrated the abnormal slit-like high signals in posterolateral putamina in three SND. The degree of cerebellar ataxia was not well correlated with cerebellar and brainstem atrophy and degeneration of pontine transverse fibers. There was a positive correlation between the atrophy of cerebellum and brainstem and the duration of cerebellar ataxia. In most of the patients with Parkinsonism, MRI demonstrated abnormal low signals in putamina on T[sub 2]-weighted images. There were positive correlations between the abnormal low signals putamina and the duration and severity of Parkinsonism. Though abnormal low signals in lateral putamina may be seen in normal aging and other disorders on T[sub 2]-weighted images, it is useful to evaluate Parkinsonism in MSA. We believe that the abnormal slit-like high signals in posterolateral putamina in MSA may suggest loss of neurons and gliosis. (author).

  11. Deep gray matter atrophy in multiple sclerosis: a tensor based morphometry.

    Science.gov (United States)

    Tao, Guozhi; Datta, Sushmita; He, Renjie; Nelson, Flavia; Wolinsky, Jerry S; Narayana, Ponnada A

    2009-07-15

    Tensor based morphometry (TBM) was applied to determine the atrophy of deep gray matter (DGM) structures in 88 relapsing multiple sclerosis (MS) patients. For group analysis of atrophy, an unbiased atlas was constructed from 20 normal brains. The MS brain images were co-registered with the unbiased atlas using a symmetric inverse consistent nonlinear registration. These studies demonstrate significant atrophy of thalamus, caudate nucleus, and putamen even at a modest clinical disability, as assessed by the expanded disability status score (EDSS). A significant correlation between atrophy and EDSS was observed for different DGM structures: (thalamus: r=-0.51, p=3.85 x 10(-7); caudate nucleus: r=-0.43, p=2.35 x 10(-5); putamen: r=-0.36, p=6.12 x 10(-6)). Atrophy of these structures also correlated with 1) T2 hyperintense lesion volumes (thalamus: r=-0.56, p=9.96 x 10(-9); caudate nucleus: r=-0.31, p=3.10 x 10(-3); putamen: r=-0.50, p=6.06 x 10(-7)), 2) T1 hypointense lesion volumes (thalamus: r=-0.61, p=2.29 x 10(-10); caudate nucleus: r=-0.35, p=9.51 x 10(-4); putamen: r=-0.43, p=3.51 x 10(-5)), and 3) normalized CSF volume (thalamus: r=-0.66, p=3.55 x 10(-12); caudate nucleus: r=-0.52, p=2.31 x 10(-7), and putamen: r=-0.66, r=2.13 x 10(-12)). More severe atrophy was observed mainly in thalamus at higher EDSS. These studies appear to suggest a link between the white matter damage and DGM atrophy in MS.

  12. Fronto-striatal atrophy in behavioural variant frontotemporal dementia & Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Maxime eBertoux

    2015-07-01

    Full Text Available Behavioural variant frontotemporal dementia (bvFTD has only recently been associated with significant striatal atrophy, whereas the striatum appears to be relatively preserved in Alzheimer’s disease (AD. Considering the critical role the striatum has in cognition and behaviour, striatal degeneration, together with frontal atrophy, could be responsible of some characteristic symptoms in bvFTD and emerges therefore as promising novel diagnostic biomarker to distinguish bvFTD and AD. Previous studies have, however, only taken either cortical or striatal atrophy into account when comparing the two diseases. In this study, we establish for the first time a profile of fronto-striatal atrophy in 23 bvFTD and 29 AD patients at presentation, based on the structural connectivity of striatal and cortical regions. Patients are compared to 50 healthy controls by using a novel probabilistic connectivity atlas, which defines striatal regions by their cortical white matter connectivity, allowing us to explore the degeneration of the frontal and striatal regions that are functionally linked. Comparisons with controls revealed that bvFTD showed substantial fronto-striatal atrophy affecting the ventral as well as anterior and posterior dorso-lateral prefrontal cortices and the related striatal subregions. By contrast, AD showed few fronto-striatal atrophy, despite having significant posterior dorso-lateral prefrontal degeneration. Direct comparison between bvFTD and AD revealed significantly more atrophy in the ventral striatal-ventromedial prefrontal cortex regions in bvFTD. Consequently, deficits in ventral fronto-striatal regions emerge as promising novel and efficient diagnosis biomarker for bvFTD. Future investigations into the contributions of these fronto-striatal loops on bvFTD symptomology are needed to develop simple diagnostic and disease tracking algorithms.

  13. Pathway to neural resilience: Self-esteem buffers against deleterious effects of poverty on the hippocampus.

    Science.gov (United States)

    Wang, Yinan; Zhang, Lin; Kong, Xiangzhen; Hong, Yingyi; Cheon, Bobby; Liu, Jia

    2016-11-01

    Human neuroimaging studies have shown that people living in poverty tend to suffer hippocampal atrophy, which leads to impaired memory and learning throughout life. However, behavioral studies demonstrate that poor people with high self-esteem are often exempt from the deleterious effect of poverty and instead possess a happy and successful life. Here we investigated whether high self-esteem can buffer against the deleterious effects of poverty, as indicated by low subjective socioeconomic status (SSS), on the hippocampal gray matter volume (GMV) in a large cohort of young participants (N = 280). As expected, findings revealed that although low (vs. high) SSS was linked with a smaller hippocampal GMV, the deleterious effect of low SSS on hippocampal GMV was alleviated when the participants have high self-esteem. Commonality analyses further confirmed this observation. The current study suggests that positive psychological resources such as self-esteem may provide protection for the hippocampal atrophy in adversity. Hum Brain Mapp 37:3757-3766, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Brain atrophy at onset and physical disability in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas

    2012-10-01

    Full Text Available The aim of this study was to investigate if brain atrophy in multiple sclerosis (MS patients during the disease onset predicts long term disability. METHODS: MS patients with follow-up time of at least 7 years from disease onset and with baseline and second magnetic resonance 12 months later were included to measure brain atrophy. Expanded Disability Status Scale (EDSS was categorized in three groups, EDSS=0, EDSS=1 and 2.5 and EDSS>2.5, and used as disability measure. RESULTS: Twenty-six patients were included. Mean atrophy during the first year in patients that reached an EDSS≥3 was -0.76±0.45 %, in patients with an EDSS between 1 and 2.5 was -0.59±0.56, while in patients with an EDSS of 0 it was -0.38±0.42 (p=0.003. DISCUSSION: Brain atrophy rates during the first year of disease were predictive of disease progression in our population.

  15. Hippocampal and Amygdalar Volumes in Dissociative Identity Disorder

    Science.gov (United States)

    Vermetten, Eric; Schmahl, Christian; Lindner, Sanneke; Loewenstein, Richard J.; Bremner, J. Douglas

    2011-01-01

    Objective Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. Method The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Results Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. Conclusions The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects. PMID:16585437

  16. Hippocampal and amygdalar volumes in dissociative identity disorder.

    Science.gov (United States)

    Vermetten, Eric; Schmahl, Christian; Lindner, Sanneke; Loewenstein, Richard J; Bremner, J Douglas

    2006-04-01

    Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects.

  17. Inter-relationships among Diet, Obesity and Hippocampal-dependent Cognitive Function

    OpenAIRE

    Davidson, Terry L.; Hargrave, Sara L.; Swithers, Susan E.; Sample, Camille H.; Fu, Xue; Kinzig, Kimberly P.; Zheng, Wei

    2013-01-01

    Intake of a Western diet (WD), which is high in saturated fat and sugar, is associated with deficits in hippocampal-dependent learning and memory processes as well as with markers of hippocampal pathology. In the present study, rats were trained to asymptote on hippocampal-dependent serial feature negative (FN) and hippocampal-independent simple discrimination problems. Performance was then assessed following 7 days on ad libitum chow and after 10, 24, 40, 60, and 90 days of maintenance on WD...

  18. MRI findings of temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Nakahara, Ichiro; Yin, Dali; Fukami, Masahiro; Kondo, Seiji; Takeuchi, Juji; Kanemoto, Kousuke; Sengoku, Akira; Kawai, Itsuo

    1992-01-01

    MRI findings were analyzed retrospectively in 46 patients with temporal lobe epilepsy in which the side of epileptogenic focus had been confirmed by EEG studies. T 1 - and T 2 -weighted images were obtained by the use of a 1.0 or 1.5 T superconducting-type MRI machine with a coronal scan perpendicular to the axis of the temporal horn of the lateral ventricle. Additional axial and sagittal scans were performed in some cases. The area of the hippocampal body was measured quantitatively using a computerized image-analysis system in 26 cases in which the hippocampus had been visualized with enough contrast on T 1 -weighted coronal images. Abnormal findings were observed in 31/46 (67%) cases. Hippocampal (HC) and temporal lobe (TL) atrophy were observed in 18/46 (39%) and 23/46 (50%) cases respectively, and the side of the atrophy corresponded with the side of the epileptogenic focus, as confirmed by EEG studies, with specificities of 89% and 74% respectively. A quantitative measurement of the area of the hippocampal body showed unilateral hippocampal atrophy more than 10% in 18/25 (69%) cases (10-25%: 10 cases, 25-50%: 7 cases, 50% 2 abnormality was observed in only 4 cases. Structural lesions were observed in 4 cases including an arachnoid cyst, an astrocytoma in amygdala, the Dandy-Walker syndrome, and tuberous sclerosis, using the more efficient imaging qualities than the CT scan. From these observations, it is apparant that superconducting MRI is extremely useful in the diagnosis of the epileptogenic topography of temporal lobe epilepsy. Particularly, hippocampal atrophy was found to correspond with the side of the epileptogenic focus on EEG with a high specificity; its quantitative evaluation could be one of the most important standards in detecting the operative indications for temporal lobe epilepsy. (author)

  19. αA crystallin may protect against geographic atrophy-meta-analysis of cataract vs. cataract surgery for geographic atrophy and experimental studies.

    Directory of Open Access Journals (Sweden)

    Peng Zhou

    Full Text Available BACKGROUND: Cataract and geographic atrophy (GA, also called advanced "dry" age-related macular degeneration are the two major causes of visual impairment in the developed world. The association between cataract surgery and the development of GA was controversial in previous studies. METHODS/PRINCIPAL FINDINGS: We performed a meta-analysis by pooling the current evidence in literature and found that cataract is associated with an increased risk of geographic atrophy with a summary odds ratio (OR of 3.75 (95% CI: 95% CI: 1.84-7.62. However, cataract surgery is not associated with the risk of geographic atrophy (polled OR=3.23, 95% CI: 0.63-16.47. Further experiments were performed to analyze how the αA-crystallin, the major component of the lens, influences the development of GA in a mouse model. We found that theαA-crystallin mRNA and protein expression increased after oxidative stress induced by NaIO(3 in immunohistochemistry of retinal section and western blot of posterior eyecups. Both functional and histopathological evidence confirmed that GA is more severe in αA-crystallin knockout mice compared to wild-type mice. CONCLUSIONS: Therefore, αA-crystallin may protect against geographic atrophy. This study provides a better understanding of the relationship between cataract, cataract surgery, and GA.

  20. Radiation-induced brain injury: A review

    Energy Technology Data Exchange (ETDEWEB)

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Wheeler, Kenneth T. [Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Department of Radiology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Chan, Michael D., E-mail: mrobbins@wakehealth.edu [Department of Radiation Oncology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States)

    2012-07-19

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  1. Radiation-induced brain injury: A review

    International Nuclear Information System (INIS)

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G.; Wheeler, Kenneth T.; Chan, Michael D.

    2012-01-01

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  2. Atomoxetine Prevents Dexamethasone-Induced Skeletal Muscle Atrophy in Mice

    Science.gov (United States)

    Jesinkey, Sean R.; Korrapati, Midhun C.; Rasbach, Kyle A.; Beeson, Craig C.

    2014-01-01

    Skeletal muscle atrophy remains a clinical problem in numerous pathologic conditions. β2-Adrenergic receptor agonists, such as formoterol, can induce mitochondrial biogenesis (MB) to prevent such atrophy. Additionally, atomoxetine, an FDA-approved norepinephrine reuptake inhibitor, was positive in a cellular assay for MB. We used a mouse model of dexamethasone-induced skeletal muscle atrophy to investigate the potential role of atomoxetine and formoterol to prevent muscle mass loss. Mice were administered dexamethasone once daily in the presence or absence of formoterol (0.3 mg/kg), atomoxetine (0.1 mg/kg), or sterile saline. Animals were euthanized at 8, 16, and 24 hours or 8 days later. Gastrocnemius muscle weights, changes in mRNA and protein expression of peroxisome proliferator–activated receptor-γ coactivator-1 α (PGC-1α) isoforms, ATP synthase β, cytochrome c oxidase subunit I, NADH dehydrogenase (ubiquinone) 1 β subcomplex, 8, ND1, insulin-like growth factor 1 (IGF-1), myostatin, muscle Ring-finger protein-1 (muscle atrophy), phosphorylated forkhead box protein O 3a (p-FoxO3a), Akt, mammalian target of rapamycin (mTOR), and ribosomal protein S6 (rp-S6; muscle hypertrophy) in naive and muscle-atrophied mice were measured. Atomoxetine increased p-mTOR 24 hours after treatment in naïve mice, but did not change any other biomarkers. Formoterol robustly activated the PGC-1α-4-IGF1–Akt-mTOR-rp-S6 pathway and increased p-FoxO3a as early as 8 hours and repressed myostatin at 16 hours. In contrast to what was observed with acute treatment, chronic treatment (7 days) with atomoxetine increased p-Akt and p-FoxO3a, and sustained PGC-1α expression and skeletal muscle mass in dexamethasone-treated mice, in a manner comparable to formoterol. In conclusion, chronic treatment with a low dose of atomoxetine prevented dexamethasone-induced skeletal muscle wasting and supports a potential role in preventing muscle atrophy. PMID:25292181

  3. Tetramethylpyrazine suppresses transient oxygen-glucose deprivation-induced connexin32 expression and cell apoptosis via the ERK1/2 and p38 MAPK pathway in cultured hippocampal neurons.

    Science.gov (United States)

    Gong, Gu; Yuan, Libang; Cai, Lin; Ran, Maorong; Zhang, Yulan; Gong, Huaqu; Dai, Xuemei; Wu, Wei; Dong, Hailong

    2014-01-01

    Tetramethylpyrazine (TMP) has been widely used in China as a drug for the treatment of various diseases. Recent studies have suggested that TMP has a protective effect on ischemic neuronal damage. However, the exact mechanism is still unclear. This study aims to investigate the mechanism of TMP mediated ischemic hippocampal neurons injury induced by oxygen-glucose deprivation (OGD). The effect of TMP on hippocampal neurons viability was detected by MTT assay, LDH release assay and apoptosis rate was measured by flow cytometry. TMP significantly suppressed neuron apoptosis in a concentration-dependent manner. TMP could significantly reduce the elevated levels of connexin32 (Cx32) induced by OGD. Knockdown of Cx32 by siRNA attenuated OGD injury. Moreover, our study showed that viability was increased in siRNA-Cx32-treated-neurons, and neuron apoptosis was suppressed by activating Bcl-2 expression and inhibiting Bax expression. Over expression of Cx32 could decrease neurons viability and increase LDH release. Furthermore, OGD increased phosphorylation of ERK1/2 and p38, whose inhibitors relieved the neuron injury and Cx32 up-regulation. Taken together, TMP can reverse the OGD-induced Cx32 expression and cell apoptosis via the ERK1/2 and p38 MAPK pathways.

  4. Tetramethylpyrazine suppresses transient oxygen-glucose deprivation-induced connexin32 expression and cell apoptosis via the ERK1/2 and p38 MAPK pathway in cultured hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Gu Gong

    Full Text Available Tetramethylpyrazine (TMP has been widely used in China as a drug for the treatment of various diseases. Recent studies have suggested that TMP has a protective effect on ischemic neuronal damage. However, the exact mechanism is still unclear. This study aims to investigate the mechanism of TMP mediated ischemic hippocampal neurons injury induced by oxygen-glucose deprivation (OGD. The effect of TMP on hippocampal neurons viability was detected by MTT assay, LDH release assay and apoptosis rate was measured by flow cytometry. TMP significantly suppressed neuron apoptosis in a concentration-dependent manner. TMP could significantly reduce the elevated levels of connexin32 (Cx32 induced by OGD. Knockdown of Cx32 by siRNA attenuated OGD injury. Moreover, our study showed that viability was increased in siRNA-Cx32-treated-neurons, and neuron apoptosis was suppressed by activating Bcl-2 expression and inhibiting Bax expression. Over expression of Cx32 could decrease neurons viability and increase LDH release. Furthermore, OGD increased phosphorylation of ERK1/2 and p38, whose inhibitors relieved the neuron injury and Cx32 up-regulation. Taken together, TMP can reverse the OGD-induced Cx32 expression and cell apoptosis via the ERK1/2 and p38 MAPK pathways.

  5. Frequency and characteristics of dual pathology in patients with lesional epilepsy.

    Science.gov (United States)

    Cendes, F; Cook, M J; Watson, C; Andermann, F; Fish, D R; Shorvon, S D; Bergin, P; Free, S; Dubeau, F; Arnold, D L

    1995-11-01

    We studied 167 patients who had identifiable lesions and temporal or extratemporal partial epilepsy. Pathology included neuronal migration disorders (NMDs) (48), low-grade tumors (52), vascular malformations (34), porencephalic cysts (16), and gliotic lesions as a result of cerebral insults early in life (17). MRI volumetric studies using thin (1.5- or 3-mm) coronal images were performed in all patients and in 44 age-matched normal controls. An atrophic hippocampal formation (HF), indicating dual pathology, was present in 25 patients (15%). Abnormal HF volumes were present in those with lesions involving temporal (17%) but also extratemporal (14%) areas. Age at onset and duration of epilepsy did not influence the presence of HF atrophy. However, febrile seizures in early childhood were more frequently, although not exclusively, found in patients with hippocampal atrophy. The frequency of hippocampal atrophy in our patients with low-grade tumors (2%) and vascular lesions (9%) was low. Dual pathology was far more common in patients with NMDs (25%), porencephalic cysts (31%), and reactive gliosis (23.5%). Some structural lesions, such as NMDs, are more likely to be associated with hippocampal atrophy, independent of the distance of the lesion from the HF. In other types of lesions, such as vascular malformations, dual pathology was found when the lesion was close to the HF. A common pathogenic mechanism during pre- or perinatal development may explain the occurrence of concomitant mesial temporal sclerosis and other structural lesions because of either (1) associated developmental abnormalities or (2) predisposition to prolonged febrile convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Diminished Dentate Gyrus Filtering of Cortical Input Leads to Enhanced Area Ca3 Excitability after Mild Traumatic Brain Injury.

    Science.gov (United States)

    Folweiler, Kaitlin A; Samuel, Sandy; Metheny, Hannah E; Cohen, Akiva S

    2018-04-06

    Mild traumatic brain injury (mTBI) disrupts hippocampal function and can lead to long-lasting episodic memory impairments. The encoding of episodic memories relies on spatial information processing within the hippocampus. As the primary entry point for spatial information into the hippocampus, the dentate gyrus is thought to function as a physiological gate, or filter, of afferent excitation before reaching downstream area Cornu Ammonis (CA3). Although injury has previously been shown to alter dentate gyrus network excitability, it is unknown whether mTBI affects dentate gyrus output to area CA3. In this study, we assessed hippocampal function, specifically the interaction between the dentate gyrus and CA3, using behavioral and electrophysiological techniques in ex vivo brain slices 1 week following mild lateral fluid percussion injury (LFPI). Behaviorally, LFPI mice were found to be impaired in an object-place recognition task, indicating that spatial information processing in the hippocampus is disrupted. Extracellular recordings and voltage-sensitive dye imaging demonstrated that perforant path activation leads to the aberrant spread of excitation from the dentate gyrus into area CA3 along the mossy fiber pathway. These results suggest that after mTBI, the dentate gyrus has a diminished capacity to regulate cortical input into the hippocampus, leading to increased CA3 network excitability. The loss of the dentate filtering efficacy reveals a potential mechanism by which hippocampal-dependent spatial information processing is disrupted, and may contribute to memory dysfunction after mTBI.

  7. Protective effect of Urtica dioica L. on renal ischemia/reperfusion injury in rat.

    Science.gov (United States)

    Sayhan, Mustafa Burak; Kanter, Mehmet; Oguz, Serhat; Erboga, Mustafa

    2012-12-01

    Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions. This study was designed to investigate the effect of Urtica dioica L. (UD), in I/R induced renal injury. A total of 32 male Sprague-Dawley rats were divided into four groups: control, UD alone, I/R and I/R + UD; each group contain 8 animals. A rat model of renal I/R injury was induced by 45-min occlusion of the bilateral renal pedicles and 24-h reperfusion. In the UD group, 3 days before I/R, UD (2 ml/kg/day intraperitoneal) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion and kidney tissues samples were obtained for histopathological investigation in all groups. To date, no more histopathological changes on intestinal I/R injury in rats by UD treatment have been reported. Renal I/R caused severe histopathological injury including tubular damage, atrophy dilatation, loss of brush border and hydropic epithelial cell degenerations, renal corpuscle atrophy, glomerular shrinkage, markedly focal mononuclear cell infiltrations in the kidney. UD treatment significantly attenuated the severity of intestinal I/R injury and significantly lowered tubulointerstitial damage score than the I/R group. The number of PCNA and TUNEL positive cells in the control and UD alone groups was negligible. When kidney sections were PCNA and TUNEL stained, there was a clear increase in the number of positive cells in the I/R group rats in the renal cortical tissues. However, there is a significant reduction in the activity of PCNA and TUNEL in kidney tissue of renal injury induced by renal I/R with UD therapy. Our results suggest that administration of UD attenuates renal I/R injury. These results suggest that UD treatment has a protective effect against renal damage induced by renal I/R. This protective effect is possibly due to its ability to inhibit I/R induced renal damage, apoptosis and cell proliferation.

  8. Changes in hippocampal volume and neuron number co-occur with memory decline in old homing pigeons (Columba livia).

    Science.gov (United States)

    Coppola, Vincent J; Kanyok, Nate; Schreiber, Austin J; Flaim, Mary E; Bingman, Verner P

    2016-05-01

    The mammalian hippocampus is particularly susceptible to age-related structural changes, which have been used to explain, in part, age-related memory decline. These changes are generally characterized by atrophy (e.g., a decrease in volume and number of synaptic contacts). Recent studies have reported age-related spatial memory deficits in older pigeons similar to those seen in older mammals. However, to date, little is known about any co-occurring changes in the aging avian hippocampal formation (HF). In the current study, it was found that the HF of older pigeons was actually larger and contained more neurons than the HF of younger pigeons, a finding that suggests that the pattern of structural changes during aging in the avian HF is different from that seen in the mammalian hippocampus. A working hypothesis for relating the observed structural changes with spatial-cognitive decline is offered. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Dyke–Davidoff–Masson syndrome with crossed cerebellar atrophy

    Directory of Open Access Journals (Sweden)

    Sanjay M. Khaladkar

    2017-09-01

    Full Text Available Dyke–Davidoff–Masson syndrome is a rare condition with classical, clinical and radiological changes – mental retardation, hemiparesis, facial asymmetry, seizures and cerebral hemiatrophy with calvarial changes. Contralateral cerebellar atrophy is rare and occurs if insult occurs after 1 month of age. We report a case of a 6-year-old female child presenting with right-sided hemiparesis, convulsions and left cerebral hemiatrophy with an old infarct in left middle cerebral artery (MCA territory, ipsilateral calvarial thickening and right (crossed cerebellar atrophy.

  10. CT features of olivopontocerebellar atrophy in children

    International Nuclear Information System (INIS)

    Kumar, S.D.; Gururaj, A.K.; Jeans, W.D.

    1995-01-01

    Between 1990 and 1992, 14 children were seen in whom a clinical diagnosis of olivopontocerebellar atrophy (OPCA) had been made. The majority of patients presented with cerebellar ataxia and hypotonia. Five children had a family history of a similar illness in first-degree relatives. All cases had undergone clinical and neurologic examinations, routine laboratory tests and cranial CT. CT features were graded to quantitative the degree of atrophy in each cerebellar hemisphere, vermis and brain stem. All patients had varying degrees of atrophic changes of cerebellum, brain stem and cerebrum. These CT features appear to be distinctive enough to enable the diagnosis of OPCA to be made. (orig.)

  11. Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Shanshan Sun

    2017-04-01

    Full Text Available Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD, a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen–glucose-deprivation/reperfusion (OGD/R model in a mouse hippocampal neuronal cell line. CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers. Using the Seahorse XFe24 Extracellular Flux Analyzer, we found that CBD significantly improved basal respiration, ATP-linked oxygen consumption rate, and the spare respiratory capacity, and augmented glucose consumption in OGD/R-injured neurons. The activation of glucose 6-phosphate dehydrogenase and the preservation of the NADPH/NADP+ ratio implies that the pentose-phosphate pathway is stimulated by CBD, thus protecting hippocampal neurons from OGD/R injury. This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.

  12. Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons.

    Science.gov (United States)

    Sun, Shanshan; Hu, Fangyuan; Wu, Jihong; Zhang, Shenghai

    2017-04-01

    Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen-glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line. CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers. Using the Seahorse XF e 24 Extracellular Flux Analyzer, we found that CBD significantly improved basal respiration, ATP-linked oxygen consumption rate, and the spare respiratory capacity, and augmented glucose consumption in OGD/R-injured neurons. The activation of glucose 6-phosphate dehydrogenase and the preservation of the NADPH/NADP + ratio implies that the pentose-phosphate pathway is stimulated by CBD, thus protecting hippocampal neurons from OGD/R injury. This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Pine needle extract prevents hippocampal memory impairment in acute restraint stress mouse model.

    Science.gov (United States)

    Lee, Jin-Seok; Kim, Hyeong-Geug; Lee, Hye-Won; Kim, Won-Yong; Ahn, Yo-Chan; Son, Chang-Gue

    2017-07-31

    The Pinus densiflora leaf has been traditionally used to treat mental health disorders as a traditional Chinese medicine. Here we examined the ethnopharmacological relevance of pine needle on memory impairment caused by stress. To elucidate the possible modulatory actions of 30% ethanolic pine needle extract (PNE) on stress-induced hippocampal excitotoxicity, we adopted an acute restraint stress mouse model. Mice were orally administered with PNE (25, 50, or 100mg/kg) or ascorbic acid (100mg/kg) for 9 days, and were then subjected to restraint stress (6h/day) for 3 days (from experimental day 7-9). To evaluate spatial cognitive and memory function, the Morris water maze was performed during experimental days 5-9. Restraint stress induced the memory impairment (the prolonged escape latency and cumulative path-length, and reduced time spent in the target quadrant), and these effects were significantly prevented by PNE treatment. The levels of corticosterone and its receptor in the sera/hippocampus were increased by restraint stress, which was normalized by PNE treatment. Restraint stress elicited the hippocampal excitotoxicity, the inflammatory response and oxidative injury as demonstrated by the increased glutamate levels, altered levels of tumor necrosis factor (TNF)-α and imbalanced oxidant-antioxidant balance biomarkers. Two immunohistochemistry activities against glial fibrillary acidic protein (GFAP)-positive astrocytes and neuronal nuclei (NeuN)-positive neurons supported the finding of excitotoxicity especially in the cornu ammonis (CA)3 region of the hippocampus. Those alterations were notably attenuated by administration of PNE. The above findings showed that PNE has pharmacological properties that modulate the hippocampal excitotoxicity-derived memory impairment under severe stress conditions. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  14. Haptoglobin is required to prevent oxidative stress and muscle atrophy.

    Directory of Open Access Journals (Sweden)

    Enrico Bertaggia

    Full Text Available BACKGROUND: Oxidative stress (OS plays a major role on tissue function. Several catabolic or stress conditions exacerbate OS, inducing organ deterioration. Haptoglobin (Hp is a circulating acute phase protein, produced by liver and adipose tissue, and has an important anti-oxidant function. Hp is induced in pro-oxidative conditions such as systemic inflammation or obesity. The role of systemic factors that modulate oxidative stress inside muscle cells is still poorly investigated. RESULTS: We used Hp knockout mice (Hp-/- to determine the role of this protein and therefore, of systemic OS in maintenance of muscle mass and function. Absence of Hp caused muscle atrophy and weakness due to activation of an atrophy program. When animals were stressed by acute exercise or by high fat diet (HFD, OS, muscle atrophy and force drop were exacerbated in Hp-/-. Depending from the stress condition, autophagy-lysosome and ubiquitin-proteasome systems were differently induced. CONCLUSIONS: Hp is required to prevent OS and the activation of pathways leading to muscle atrophy and weakness in normal condition and upon metabolic challenges.

  15. Dominant inherited distal spinal muscular atrophy with atrophic and hypertrophic calves

    NARCIS (Netherlands)

    Groen, R J; Sie, O G; van Weerden, T W

    The clinical, electrophysiological, radiological and morphological data of 3 members of a family with autosomal dominant distal spinal muscular atrophy (DSMA) are reported. One patient has the clinical picture of peroneal muscular atrophy with atrophic calves. His father and sister suffer from

  16. Prevention of pectus excavatum for children with spinal muscular atrophy type 1.

    Science.gov (United States)

    Bach, John R; Bianchi, Carlo

    2003-10-01

    To demonstrate the elimination of pectus excavatum and promotion of more normal lung growth and chest wall development by the use of high-span positive inspiratory pressure plus positive end-expiratory pressure (PIP+PEEP), patients with spinal muscular atrophy type 1 with paradoxical breathing were placed on high-span PIP+PEEP when sleeping from the point of diagnosis of spinal muscular atrophy. Although the appearance of pectus excavatum is ubiquitous in untreated infants with spinal muscular atrophy type 1, after institution of high-span PIP+PEEP, pectus resolves and lungs and chest walls grow more normally. High-span PIP+PEEP is indicated for all infants diagnosed with spinal muscular atrophy who demonstrate paradoxical breathing for the purpose of promoting more normal lung and chest development.

  17. Spinal Cord Gray Matter Atrophy in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Paquin, M-Ê; El Mendili, M M; Gros, C; Dupont, S M; Cohen-Adad, J; Pradat, P-F

    2018-01-01

    There is an emerging need for biomarkers to better categorize clinical phenotypes and predict progression in amyotrophic lateral sclerosis. This study aimed to quantify cervical spinal gray matter atrophy in amyotrophic lateral sclerosis and investigate its association with clinical disability at baseline and after 1 year. Twenty-nine patients with amyotrophic lateral sclerosis and 22 healthy controls were scanned with 3T MR imaging. Standard functional scale was recorded at the time of MR imaging and after 1 year. MR imaging data were processed automatically to measure the spinal cord, gray matter, and white matter cross-sectional areas. A statistical analysis assessed the difference in cross-sectional areas between patients with amyotrophic lateral sclerosis and controls, correlations between spinal cord and gray matter atrophy to clinical disability at baseline and at 1 year, and prediction of clinical disability at 1 year. Gray matter atrophy was more sensitive to discriminate patients with amyotrophic lateral sclerosis from controls ( P = .004) compared with spinal cord atrophy ( P = .02). Gray matter and spinal cord cross-sectional areas showed good correlations with clinical scores at baseline ( R = 0.56 for gray matter and R = 0.55 for spinal cord; P amyotrophic lateral sclerosis. © 2018 by American Journal of Neuroradiology.

  18. Canine hippocampal formation composited into three-dimensional structure using MPRAGE.

    Science.gov (United States)

    Jung, Mi-Ae; Nahm, Sang-Soep; Lee, Min-Su; Lee, In-Hye; Lee, Ah-Ra; Jang, Dong-Pyo; Kim, Young-Bo; Cho, Zang-Hee; Eom, Ki-Dong

    2010-07-01

    This study was performed to anatomically illustrate the living canine hippocampal formation in three-dimensions (3D), and to evaluate its relationship to surrounding brain structures. Three normal beagle dogs were scanned on a MR scanner with inversion recovery segmented 3D gradient echo sequence (known as MP-RAGE: Magnetization Prepared Rapid Gradient Echo). The MRI data was manually segmented and reconstructed into a 3D model using the 3D slicer software tool. From the 3D model, the spatial relationships between hippocampal formation and surrounding structures were evaluated. With the increased spatial resolution and contrast of the MPRAGE, the canine hippocampal formation was easily depicted. The reconstructed 3D image allows easy understanding of the hippocampal contour and demonstrates the structural relationship of the hippocampal formation to surrounding structures in vivo.

  19. Brain atrophy in Huntington's disease: A CT-scan study

    International Nuclear Information System (INIS)

    Starkstein, S.E.; Folstein, S.E.; Brandt, J.; McDonnell, A.; Folstein, M.

    1989-01-01

    CT-scan measurements of cortical and subcortical atrophy were carried out in 34 patients with Huntington's disease (HD). While a significant correlation was observed between parameters of subcortical atrophy (bicaudate ratio, bifrontal ratio and third ventricular ratio) and duration of the disease, there was no significant correlation between these parameters and age. On the other hand, measurements of cortical atrophy (frontal fissure ratio and cortical sulci ratio) correlated significantly with age but not with duration of the disease. When a group of 24 HD patients were compared on CT-scan measurements with a group of 24 age-matched normal controls, significant differences were obtained for all the variables examined, but the bicaudate ratio showed the highest sensitivity and specificity. Even mildly affected patients, with duration of motor symptoms less than 3 years had higher bicaudate ratios than age-matched controls. (orig.)

  20. Recommendations for the management of postmenopausal vaginal atrophy

    DEFF Research Database (Denmark)

    Sturdee, D W; Panay, N; Ulrich, Lian

    2010-01-01

    for hormone replacement therapy (HRT) over recent years that has suggested an increased risk of breast cancer, heart disease and stroke. But, regardless of whether these scares are justified, local treatment of vaginal atrophy is not associated with these possible risks of systemic HRT. Other reasons...... dryness can be helped by simple lubricants but the best and most logical treatment for urogenital atrophy is to use local estrogen. This is safe, effective and with few contraindications. It is hoped that these guidelines and recommendations, produced to coincide with World Menopause Day 2010, will help...

  1. Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

    Science.gov (United States)

    Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

    2017-10-01

    We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition

  2. Progressive Diaphragm Atrophy in Pediatric Acute Respiratory Failure.

    Science.gov (United States)

    Glau, Christie L; Conlon, Thomas W; Himebauch, Adam S; Yehya, Nadir; Weiss, Scott L; Berg, Robert A; Nishisaki, Akira

    2018-02-05

    Diaphragm atrophy is associated with delayed weaning from mechanical ventilation and increased mortality in critically ill adults. We sought to test for the presence of diaphragm atrophy in children with acute respiratory failure. Prospective, observational study. Single-center tertiary noncardiac PICU in a children's hospital. Invasively ventilated children with acute respiratory failure. Diaphragm thickness at end-expiration and end-inspiration were serially measured by ultrasound in 56 patients (median age, 17 mo; interquartile range, 5.5-52), first within 36 hours of intubation and last preceding extubation. The median duration of mechanical ventilation was 140 hours (interquartile range, 83-201). At initial measurement, thickness at end-expiration was 2.0 mm (interquartile range, 1.8-2.5) and thickness at end-inspiration was 2.5 mm (interquartile range, 2-2.8). The change in thickness at end-expiration during mechanical ventilation between first and last measurement was -13.8% (interquartile range, -27.4% to 0%), with a -3.4% daily atrophy rate (interquartile range, -5.6 to 0%). Thickening fraction = ([thickness at end-inspiration - thickness at end-expiration]/thickness at end-inspiration) throughout the course of mechanical ventilation was linearly correlated with spontaneous breathing fraction (beta coefficient, 9.4; 95% CI, 4.2-14.7; p = 0.001). For children with a period of spontaneous breathing fraction less than 0.5 during mechanical ventilation, those with exposure to a continuous neuromuscular blockade infusion (n = 15) had a significantly larger decrease in thickness at end-expiration compared with children with low spontaneous breathing fraction who were not exposed to a neuromuscular blockade infusion (n = 18) (-16.4%, [interquartile range, -28.4% to -7.0%] vs -7.3%; [interquartile range, -10.9% to -0%]; p = 0.036). Diaphragm atrophy is present in children on mechanical ventilation for acute respiratory failure. Diaphragm contractility, measured as

  3. Longitudinal study of hippocampal volumes in heavy cannabis users.

    Science.gov (United States)

    Koenders, L; Lorenzetti, V; de Haan, L; Suo, C; Vingerhoets, Wam; van den Brink, W; Wiers, R W; Meijer, C J; Machielsen, Mwj; Goudriaan, A E; Veltman, D J; Yücel, M; Cousijn, J

    2017-08-01

    Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes. Twenty heavy cannabis users (mean age 21 years, range 18-24 years) and 23 matched non-cannabis using healthy controls were submitted to a comprehensive psychological assessment and magnetic resonance imaging scan at baseline and at follow-up (average of 39 months post-baseline; standard deviation=2.4). Cannabis users started smoking around 16 years and smoked on average five days per week. A novel aspect of the current study is that hippocampal volume estimates were obtained from manual tracing the hippocampus on T1-weighted anatomical magnetic resonance imaging scans, using a previously validated protocol. Compared to controls, cannabis users did not show hippocampal volume alterations at either baseline or follow-up. Hippocampal volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippocampal volumes. Continued heavy cannabis use did not affect hippocampal neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in samples of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy.

  4. Effects of acute restraint-induced stress on glucocorticoid receptors and brain-derived neurotrophic factor after mild traumatic brain injury.

    Science.gov (United States)

    Griesbach, G S; Vincelli, J; Tio, D L; Hovda, D A

    2012-05-17

    We have previously reported that experimental mild traumatic brain injury results in increased sensitivity to stressful events during the first post-injury weeks, as determined by analyzing the hypothalamic-pituitary-adrenal (HPA) axis regulation following restraint-induced stress. This is the same time period when rehabilitative exercise has proven to be ineffective after a mild fluid-percussion injury (FPI). Here we evaluated effects of stress on neuroplasticity. Adult male rats underwent either an FPI or sham injury. Additional rats were only exposed to anesthesia. Rats were exposed to 30 min of restraint stress, followed by tail vein blood collection at post-injury days (PID) 1, 7, and 14. The response to dexamethasone (DEX) was also evaluated. Hippocampal tissue was collected 120 min after stress onset. Brain-derived neurotrophic factor (BDNF) along with glucocorticoid (GR) and mineralocorticoid (MR) receptors was determined by Western blot analysis. Results indicated injury-dependent changes in glucocorticoid and mineralocorticoid receptors that were influenced by the presence of dexamethasone. Control and FPI rats responded differentially to DEX in that GR increases after receiving the lower dose of DEX were longer lasting in the FPI group. A suppression of MR was found at PID 1 in vehicle-treated FPI and Sham groups. Decreases in the precursor form of BDNF were observed in different FPI groups at PIDs 7 and 14. These findings suggest that the increased sensitivity to stressful events during the first post-injury weeks, after a mild FPI, has an impact on hippocampal neuroplasticity. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy

    DEFF Research Database (Denmark)

    Suetta, Charlotte Arneboe; Frandsen, Ulrik; Jensen, Line

    2012-01-01

    Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle...... atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2......-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1α and PGC-1β (1-4 days) and a ∼10% decrease in myofiber size (4 days). Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days) of immobilization. In contrast...

  6. The diagnosis of thymoma and thymic atrophy in patients with myasthenia gravis

    International Nuclear Information System (INIS)

    Sund, K.K.; Skeie, G.O.; Gilhus, N.E.; Aarli, J.A.; Varhaug, J.E.

    1997-01-01

    The authors have compared clinical, immunological and radiological data in 20 patients with myasthenia gravis and thymoma and in 21 patients with myasthenia gravis and thymic atrophy. The median age at onset was 54 years in the thymoma group and 63 years in the thymic atrophy group. The severity of the disease was similar in the two groups, and there was no significant difference in the concentration of acetylcholine receptor antibodies. CA antibodies were demonstrated in 17/20 thymoma patients and in 6/21 with thymic atrophy, while 19/20 thymoma patients had antibodies to titin, compared with 9/21 among those with thymic atrophy. The diagnosis and treatment of patients with myasthenia gravis is based upon an evaluation of clinical, immunological and radiological data. 28 refs., 2 tabs

  7. The relationship between tear severity, fatty infiltration, and muscle atrophy in the supraspinatus.

    Science.gov (United States)

    Barry, Jeffrey J; Lansdown, Drew A; Cheung, Sunny; Feeley, Brian T; Ma, C Benjamin

    2013-01-01

    Fatty infiltration and muscle atrophy have been described as interrelated characteristic changes that occur within the muscles of the rotator cuff after cuff tears, and both are independently associated with poor outcomes after surgical repair. We hypothesize that fatty infiltration and muscle atrophy are two distinct processes independently associated with supraspinatus tears. A retrospective review of 377 patients who underwent shoulder magnetic resonance imaging at one institution was performed. Multivariate analysis was performed based on parameters including age, sex, rotator cuff tear severity, fatty infiltration grade, and muscle atrophy. A total of 116 patients (30.8%) had full-thickness tears of the supraspinatus, 153 (40.6%) had partial thickness tears, and 108 (28.7%) had no evidence of tear. With increasing tear severity, the prevalence of substantial fatty infiltration (grade ≥2) increased: 6.5% of patients with no tears vs 41.4% for complete tears (P tear severity: 36.1% of no tears vs 77.6% of complete tears (P muscle atrophy when taking into account sex, age, and tear severity. Fatty infiltration and muscle atrophy are independently associated processes. Fatty infiltration is also related to increasing age, muscle tear severity, and sex, whereas muscle atrophy is related to increasing age but not tear severity. In patients without rotator cuff tears, fatty infiltration and atrophy prevalence increased independently with increasing age. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  8. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Vis, J.B. de; Zwanenburg, J.J.; Kleij, L.A. van der; Spijkerman, J.M.; Hendrikse, J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Biessels, G.J. [University Medical Center Utrecht, Department of Neurology, Brain Center Rudolf Magnus, Utrecht (Netherlands); Petersen, E.T. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Hvidovre Hospital, Danish Research Centre for Magnetic Resonance, Hvidovre (Denmark)

    2016-05-15

    To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T{sub 2} of the CSF relates to brain atrophy. Twenty-eight subjects [mean age 64 (sd 2) years] were included; T{sub 1}-weighted and CSF MRI were performed. The first echo data of the CSF MRI sequence was used to obtain intracranial volume, CSF partial volume was measured voxel-wise to obtain CSF volume (V{sub CSF}) and the T{sub 2} of CSF (T{sub 2,CSF}) was calculated. The correlation between V{sub CSF} / T{sub 2,CSF} and brain atrophy scores [global cortical atrophy (GCA) and medial temporal lobe atrophy (MTA)] was evaluated. Relative total, peripheral subarachnoidal, and ventricular V{sub CSF} increased significantly with increased scores on the GCA and MTA (R = 0.83, 0.78 and 0.78 and R = 0.72, 0.62 and 0.86). Total, peripheral subarachnoidal, and ventricular T{sub 2} of the CSF increased significantly with higher scores on the GCA and MTA (R = 0.72, 0.70 and 0.49 and R = 0.60, 0.57 and 0.41). A fast, fully automated CSF MRI volumetric sequence is an alternative for qualitative atrophy scales. The T{sub 2} of the CSF is related to brain atrophy and could thus be a marker of neurodegenerative disease. (orig.)

  9. Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD and Alzheimer's disease (AD

    Directory of Open Access Journals (Sweden)

    Dong Seok Yi

    Full Text Available ABSTRACT Behavioural disturbances in frontotemporal dementia (FTD are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. Objective: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD. Methods: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R and Frontal System Behaviour Scale (FrSBe. Atrophy in prefrontal (VMPFC, DLPFC and striatal (caudate, putamen regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. Results: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. Conclusion: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

  10. Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy

    Science.gov (United States)

    Yakabe, Mitsutaka; Ota, Hidetaka; Iijima, Katsuya; Eto, Masato; Ouchi, Yasuyoshi; Akishita, Masahiro

    2018-01-01

    Background Interleukin-6 (IL-6) is an inflammatory cytokine. Whether systemic IL-6 affects atrogene expression and disuse-induced skeletal muscle atrophy is unclear. Methods Tail-suspended mice were used as a disuse-induced muscle atrophy model. We administered anti-mouse IL-6 receptor antibody, beta-hydroxy-beta-methylbutyrate (HMB) and vitamin D to the mice and examined the effects on atrogene expression and muscle atrophy. Results Serum IL-6 levels were elevated in the mice. Inhibition of IL-6 receptor suppressed muscle RING finger 1 (MuRF1) expression and prevented muscle atrophy. HMB and vitamin D inhibited the serum IL-6 surge, downregulated the expression of MuRF1 and atrogin-1 in the soleus muscle, and ameliorated atrophy in the mice. Conclusion Systemic IL-6 affects MuRF1 expression and disuse-induced muscle atrophy. PMID:29351340

  11. Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy.

    Directory of Open Access Journals (Sweden)

    Mitsutaka Yakabe

    Full Text Available Interleukin-6 (IL-6 is an inflammatory cytokine. Whether systemic IL-6 affects atrogene expression and disuse-induced skeletal muscle atrophy is unclear.Tail-suspended mice were used as a disuse-induced muscle atrophy model. We administered anti-mouse IL-6 receptor antibody, beta-hydroxy-beta-methylbutyrate (HMB and vitamin D to the mice and examined the effects on atrogene expression and muscle atrophy.Serum IL-6 levels were elevated in the mice. Inhibition of IL-6 receptor suppressed muscle RING finger 1 (MuRF1 expression and prevented muscle atrophy. HMB and vitamin D inhibited the serum IL-6 surge, downregulated the expression of MuRF1 and atrogin-1 in the soleus muscle, and ameliorated atrophy in the mice.Systemic IL-6 affects MuRF1 expression and disuse-induced muscle atrophy.

  12. Organotypic hippocampal slice cultures for studies of brain damage, neuroprotection and neurorepair

    DEFF Research Database (Denmark)

    Noraberg, Jens; Poulsen, Frantz Rom; Blaabjerg, Morten

    2005-01-01

    Slices of developing brain tissue can be grown for several weeks as so-called organotypic slice cultures. Here we summarize and review studies using hippocampal slice cultures to investigate mechanisms and treatment strategies for the neurodegenerative disorders like stroke (cerebral ischemia......), Alzheimer's disease (AD) and epilepsia. Studies of non-excitotoxic neurotoxic compounds and the experimental use of slice cultures in studies of HIV neurotoxicity, traumatic brain injury (TBI) and neurogenesis are included. For cerebral ischemia, experimental models with oxygen-glucose deprivation (OGD......) and exposure to glutamate receptor agonists (excitotoxins) are reviewed. For epilepsia, focus is on induction of seizures with effects on neuronal loss, axonal sprouting and neurogenesis. For Alzheimer's disease, the review centers on the use of beta-amyloid (Abeta) in different models, while the section...

  13. Brain atrophy and lesion load predict long term disability in multiple sclerosis

    DEFF Research Database (Denmark)

    Popescu, Veronica; Agosta, Federica; Hulst, Hanneke E

    2013-01-01

    To determine whether brain atrophy and lesion volumes predict subsequent 10 year clinical evolution in multiple sclerosis (MS).......To determine whether brain atrophy and lesion volumes predict subsequent 10 year clinical evolution in multiple sclerosis (MS)....

  14. [Protective effect of pretreatment of Salvia miltiorrhiza Bunge. f. alba plasma against oxygen-glucose deprivation-induced injury of cultured rat hippocampal neurons by inhibiting apoptosis].

    Science.gov (United States)

    Li, Mei-Yi; Zhang, Yan-Bo; Zuo, Huan; Liu, Li-Li; Niu, Jing-Zhong

    2012-02-25

    The present study was to investigate the effect of Salvia miltiorrhiza Bunge. f. alba (SMA) pharmacological pretreatment on apoptosis of cultured hippocampal neurons from neonate rats under oxygen-glucose deprivation (OGD). Cultured hippocampal neurons were randomly divided into five groups (n = 6): normal plasma group, low dose SMA plasma (2.5%) group, middle dose SMA plasma (5%) group, high dose SMA plasma (10%) group and control group. The hippocampal neurons were cultured and treated with plasma from adult Wistar rats intragastrically administered with saline or aqueous extract of SMA. The apoptosis of neurons was induced by glucose-free Earle's solution containing 1 mmol/L Na2S2O4 and labeled by MTT and Annexin V/PI double staining. Moreover, protein expressions of Bcl-2 and Bax were detected by immunofluorescence. The results showed that few apoptotic cells were observed in control group, whereas the number of apoptotic cells was greatly increased in normal plasma group and low dose SMA plasma group. Both middle and high dose SMA plasma could protect cultured hippocampal neurons from apoptosis induced by OGD (P control, normal plasma and low dose SMA plasma groups, middle and high dose SMA plasma groups both showed significantly higher levels of Bcl-2 (P neurons by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax.

  15. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy

    DEFF Research Database (Denmark)

    De Vis, J B; Zwanenburg, J J; van der Kleij, L A

    2016-01-01

    OBJECTIVES: To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T2 of the CSF relates to brain atrophy. METHODS: Twenty-eight subjects [mean age 64 (sd 2) years] were included; T1-weighted and CSF MRI were......) and medial temporal lobe atrophy (MTA)] was evaluated. RESULTS: Relative total, peripheral subarachnoidal, and ventricular VCSF increased significantly with increased scores on the GCA and MTA (R = 0.83, 0.78 and 0.78 and R = 0.72, 0.62 and 0.86). Total, peripheral subarachnoidal, and ventricular T2...... be a marker of neurodegenerative disease. KEY POINTS: • A 1:11 min CSF MRI volumetric sequence can evaluate brain atrophy. • CSF MRI provides accurate atrophy assessment without partial volume effects. • CSF MRI data can be processed quickly without user interaction. • The measured T 2 of the CSF is related...

  16. Changes in hippocampal metabolites after effective treatment for fibromyalgia: a case study.

    Science.gov (United States)

    Wood, Patrick B; Ledbetter, Christina R; Patterson, James C

    2009-01-01

    Fibromyalgia has been associated with disrupted hippocampal brain metabolite ratios by studies using single voxel magnetic resonance spectroscopy (1H-MRS). Exposure to stress is considered a risk factor for the development and exacerbation of fibromyalgia symptoms. Basic science has demonstrated the hippocampus to be exquisitely sensitive to the effects of stressful experience, which results in changes including alterations in metabolite content and frank atrophy. This report details the case of a 47-year-old woman with fibromyalgia who was originally found to have a profound depression of the ratio of N-acetylaspartate to creatine in her right hippocampus during participation in a study to assess brain metabolite disturbances in fibromyalgia utilizing single voxel proton magnetic resonance spectroscopy. An individualized treatment strategy was developed based both on physiological abnormalities associated with the disorder and symptoms that characterized the patient's unique clinical profile. Clinical and spectroscopic evaluation following nine months of treatment demonstrated both an improvement in her clinical profile and normalization of the NAA/Cr ratio within her right hippocampus. Therapeutic strategies aimed at demonstrable lesions associated with fibromyalgia appear to represent rational targets for pharmacological intervention. The rationale for development of novel pharmacotherapies for this unusual disorder is discussed.

  17. [(11)C]PIB-, [(18)F]FDG-PET and MRI imaging in patients with Parkinson's disease with and without dementia

    DEFF Research Database (Denmark)

    Jokinen, Pekka; Scheinin, Noora; Aalto, Sargo

    2010-01-01

    and controls, and hippocampal atrophy was associated with impaired memory. This cross-sectional data suggests that development of dementia in PD is associated with extensive spread of hypometabolism beyond the occipital cortex, and with hippocampal and frontal atrophy but not beta-amyloid deposition consistent...... impairment and dementia in PD. We performed a neuropsychological evaluation, structural brain MRI, [(18)F]FDG PET and [(11)C]PIB PET in 19 PD patients [eight non-demented (PD), eleven demented (PDD)] and 24 healthy elderly volunteers. [(11)C]PIB region-to-cerebellum ratios did not differ significantly...... between the groups in any brain region (p > 0.05). PDD patients showed impaired glucose metabolism in cortical brain regions and this reduction was associated with the degree of cognitive impairment. PDD patients had more atrophy both in the hippocampus and the frontal cortex compared with PD patients...

  18. Global gray matter changes in posterior cortical atrophy: A serial imaging study

    NARCIS (Netherlands)

    Lehmann, M.; Barnes, J.; Ridgway, G.R.; Ryan, N.S.; Warrington, E.K.; Crutch, S.J.; Fox, N.C.

    2012-01-01

    Background: Posterior cortical atrophy (PCA) is a neurodegenerative condition predominantly associated with Alzheimer's disease (AD) pathology. Cross-sectional imaging studies have shown different atrophy patterns in PCA patients compared with typical amnestic Alzheimer's disease (tAD) patients,

  19. Spatial deficits in an amnesic patient with hippocampal damage: questioning the multiple trace theory.

    Science.gov (United States)

    Gomez, A; Rousset, S; Charnallet, A

    2012-06-01

    Mediotemporal lobe structures are involved in both spatial processing and long-term memory. Patient M.R. suffers from amnesia, due to bilateral hippocampal lesion and temporoparietal atrophy following carbon monoxide poisoning. We compared his performance in immediate spatial memory tasks with the performance of ten healthy matched participants. Using an immediate reproduction of path, we observed a dissociation between his performance in three allocentric tasks and in five egocentric-updating tasks. His performance was always impaired on tasks requiring the use of an egocentric-updating representation but remained preserved on allocentric tasks. These results fit with the hypothesis that the hippocampus plays a role in spatial memory, but they also suggest that allocentric deficits previously observed in amnesia might actually reflect deficits in egocentric-updating processes. Furthermore, the co-occurrence of deficits in episodic long-term memory and short-term egocentric-updating representation without any short-term allocentric deficit suggests a new link between the mnemonic and navigational roles of the hippocampus. The Cognitive Map theory, the Multiple Trace theory, as well as further models linking spatial and nonspatial functions of the hippocampus are discussed. Copyright © 2011 Wiley Periodicals, Inc.

  20. The hippocampal formation: morphological changes induced by thyroid, gonadal and adrenal hormones.

    Science.gov (United States)

    Gould, E; Woolley, C S; McEwen, B S

    1991-01-01

    The hippocampal formation is of considerable interest due to its proposed role in a number of important functions, including learning and memory processes. Manipulations of thyroid, gonadal and adrenal hormones have been shown to influence hippocampal physiology as well as learning and memory. The cellular events which underlie these hormone-induced functional changes are largely unexplored. However, studies suggest that hormonal manipulations during development and in adulthood result in dramatic morphological changes within the hippocampal formation. Because neuronal physiology has been suggested to depend upon neuronal morphology, we have been determining the morphologic sensitivity of hippocampal neurons to thyroid and steroid hormones in an effort to elucidate possible structural mechanisms to account for differences in hippocampal function. In this review, hormone-induced structural changes in the developing and adult hippocampal formation are discussed, with particular emphasis on their functional relevance. Sex differences, as well as the developmental effects of thyroid hormone and glucocorticoids, are described. Moreover, the effects of ovarian steroids, thyroid hormone and glucocorticoids on neuronal morphology in the hippocampal formation of the adult rat are reviewed. These hormone-induced structural changes may account, at least in part, for previously reported hormone-induced changes in hippocampal function.

  1. MR imaging findings in patients with epilepsy

    International Nuclear Information System (INIS)

    Honghan, Gong; Hiraishi, Kumiko; Matsuoka, Takae

    1994-01-01

    We retrospectively examined the MR imaging (MRI) findings in 144 patients with epilepsy (31 with temporal lobe epilepsy and 113 with other epilepsies). 110 cases (76.4%) showed abnormal findings such as spotty lesions in white matter, hippocampal atrophy and/or signal change, ventricular dilatation and/or deformity, developmental lesions, brain tumors and so on. Hippocampal atrophy and/or signal change was shown in 74.1% of temporal lobe epilepsy, a remarkably high percentage (p<0.01) compared with the other types of epilepsies (18.1%). This finding means that hippocampal lesions may play a large part in the cause of temporal lobe epilepsy. Investigation of the relationship between clinical term and abnormal findings revealed that the longer the clinical term, the large the number of hippocampal lesions, regardless of whether it is temporal lobe epilepsy or not. Thus hippocampal lesions may occur as a result of hypoxia accompanied with seizure. Therefore we recommend horizontal and/or vertical sections of hippocampus in MR imaging of all patients with epilepsy. Even though MR finding may reflect some secondary lesions, MRI will shed some light on the proper understanding of epilepsy. (author)

  2. Study on cognition disorder and morphologic change of neurons in hippocampus area following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    洪军; 崔建忠; 周云涛; 高俊玲

    2002-01-01

    Objective: To explore the correlation between cognition disorder and morphologic change of hippocampal neurons after traumatic brain injury (TBI).   Methods: Wistar rat models with severe TBI were made by Marmarous method. The histopathological change of the neurons in the hippocampus area were studied with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated X-dUPT nick end labeling (TUNEL), respectively. The cognitive function was evaluated with the Morris water maze test.   Results: The comprehensive neuronal degeneration and necrosis could be observed in CA2-3 regions of hippocampus at 3 days after injury. Apoptotic positive neurons in CA2-4 regions of hippocampus and dentate gyrus increased in the injured group at 24 hours following TBI. They peaked at 7 days and then declined. Significant impairment of spatial learning and memory was observed after injury in the rats.   Conclusions: The rats have obvious disorders in spatial learning and memory after severe TBI. Meanwhile, delayed neuronal necrosis and apoptosis can be observed in the neurons in the hippocampus area. It suggests that delayed hippocampal cell death may contribute to the functional deficit.

  3. A proteomics study of hyperhomocysteinemia injury of the hippocampal neurons using iTRAQ.

    Science.gov (United States)

    Fang, Min; Wang, Jing; Yan, Han; Zhao, Yan-Xin; Liu, Xue-Yuan

    2014-11-01

    High levels of homocysteine, caused by abnormal methionine metabolism, can induce degeneration of mouse hippocampal neurons. iTRAQ™ technology has been widely used in the field of proteomics research and through employing this technology, the present study identified that hyperhomocysteinemia induced the downregulation of 52 proteins and upregulation of 44 proteins in the mouse hippocampus. Through gene ontology and pathway analysis, the upregulation of components of the cytoskeleton, actin, regulators of focal adhesion, calcium signaling pathways, tight junctions, ErbB and gonadotrophin‑releasing hormone signaling, leukocyte, transendothelial migration, propanoate and pyruvate metabolism, valine, leucine and isoleucine biosynthesis, synthesis and degradation of ketone bodies and benzoate degradation via CoA ligation pathway, was identified. It was additionally verified that tau protein was highly expressed in the hyperhomocysteinemic neurons. Further analysis revealed that tau network proteins played functional roles in homocysteine‑induced neuronal damage.

  4. Three-Dimensional Culture Model of Skeletal Muscle Tissue with Atrophy Induced by Dexamethasone.

    Science.gov (United States)

    Shimizu, Kazunori; Genma, Riho; Gotou, Yuuki; Nagasaka, Sumire; Honda, Hiroyuki

    2017-06-15

    Drug screening systems for muscle atrophy based on the contractile force of cultured skeletal muscle tissues are required for the development of preventive or therapeutic drugs for atrophy. This study aims to develop a muscle atrophy model by inducing atrophy in normal muscle tissues constructed on microdevices capable of measuring the contractile force and to verify if this model is suitable for drug screening using the contractile force as an index. Tissue engineered skeletal muscles containing striated myotubes were prepared on the microdevices for the study. The addition of 100 µM dexamethasone (Dex), which is used as a muscle atrophy inducer, for 24 h reduced the contractile force significantly. An increase in the expression of Atrogin-1 and MuRF-1 in the tissues treated with Dex was established. A decrease in the number of striated myotubes was also observed in the tissues treated with Dex. Treatment with 8 ng/mL Insulin-like Growth Factor (IGF-I) for 24 h significantly increased the contractile force of the Dex-induced atrophic tissues. The same treatment, though, had no impact on the force of the normal tissues. Thus, it is envisaged that the atrophic skeletal muscle tissues induced by Dex can be used for drug screening against atrophy.

  5. Consideration of the method of image diagnosis with respect to frontal lobe atrophy

    Science.gov (United States)

    Sato, K.; Sugawara, K.; Narita, Y.; Namura, I.

    1996-12-01

    Proposes a segmentation method for a quantitative image diagnosis as a means of realizing an objective diagnosis of the frontal lobe atrophy. From the data obtained on the grade of membership, the fractal dimensions of the cerebral tissue [cerebral spinal fluid (CSF), gray matter, and white matter] and the contours are estimated. The mutual relationship between the degree of atrophy and the fractal dimension has been analyzed based on the estimated fractal dimensions. Using a sample of 42 male and female cases, ranging In age from 50's to 70's, it has been concluded that the frontal lobe atrophy can be quantified by regarding it as an expansion of CSF region on the magnetic resonance imaging (MRI) of the brain. Furthermore, when the process of frontal lobe atrophy is separated into early and advanced stages, the volumetric change of CSF and white matter in frontal lobe displays meaningful differences between the two stages, demonstrating that the fractal dimension of CSF rises with the progress of atrophy. Moreover, an interpolation method for three-dimensional (3-D) shape reconstruction of the region of diagnostic interest is proposed and 3-D shape visualization, with respect to the degree and form of atrophy, is performed on the basis of the estimated fractal dimension of the segmented cerebral tissue.

  6. Food strategies of renal atrophy based on Avicenna and conventional medicine

    Directory of Open Access Journals (Sweden)

    Marjan Mahjour

    2017-10-01

    Full Text Available Kidneys have an important role in the body. Any damage to kidney role can damage many organs of the body. Traditional Persian Medicine (TPM or Iranian traditional medicine (ITM is an ancient temperamental medicine with many literatures about kidney diseases and Avicenna (980–1025 AD describes kidney diseases in details. This is a review study by searching of the most important clinical and pharmaceutical TPM textbooks such as The Canon of Medicine by Avicenna and scientific data banks using keywords such as “Hozal-e-Kolye”, renal atrophy, tubular atrophy, kidney, chronic kidney disease, and end stage renal disease. This paper found that “Hozal-e-Kolye” in TPM texts is the same tubular atrophy in conventional medicine due to some similar symptoms between them. Lifestyle modification and use of proposed foodstuffs can be considered as a complementary medicine in addition to conventional treatments to manage these patients. TPM scholars prescribed some foodstuffs such as camel milk, sheep's milk and Ficus carica for this disease as a complementary management. This study aimed to explain HK (the same tubular atrophy considering their similar symptoms and introduce some foodstuffs. It seems using of foodstuffs affecting tubular atrophy based on TPM literatures can has a role as a supplemental method in company with conventional medicine management.

  7. Skeletal muscle atrophy in bioengineered skeletal muscle: a new model system.

    Science.gov (United States)

    Lee, Peter H U; Vandenburgh, Herman H

    2013-10-01

    Skeletal muscle atrophy has been well characterized in various animal models, and while certain pathways that lead to disuse atrophy and its associated functional deficits have been well studied, available drugs to counteract these deficiencies are limited. An ex vivo tissue-engineered skeletal muscle offers a unique opportunity to study skeletal muscle physiology in a controlled in vitro setting. Primary mouse myoblasts isolated from adult muscle were tissue engineered into bioartificial muscles (BAMs) containing hundreds of aligned postmitotic muscle fibers expressing sarcomeric proteins. When electrically stimulated, BAMs generated measureable active forces within 2-3 days of formation. The maximum isometric tetanic force (Po) increased for ∼3 weeks to 2587±502 μN/BAM and was maintained at this level for greater than 80 days. When BAMs were reduced in length by 25% to 50%, muscle atrophy occurred in as little as 6 days. Length reduction resulted in significant decreases in Po (50.4%), mean myofiber cross-sectional area (21.7%), total protein synthesis rate (22.0%), and noncollagenous protein content (6.9%). No significant changes occurred in either the total metabolic activity or protein degradation rates. This study is the first in vitro demonstration that length reduction alone can induce skeletal muscle atrophy, and establishes a novel in vitro model for the study of skeletal muscle atrophy.

  8. Higher-order conditioning is impaired by hippocampal lesions.

    Science.gov (United States)

    Gilboa, Asaf; Sekeres, Melanie; Moscovitch, Morris; Winocur, Gordon

    2014-09-22

    Behavior in the real world is rarely motivated by primary conditioned stimuli that have been directly associated with potent unconditioned reinforcers. Instead, motivation and choice behavior are driven by complex chains of higher-order associations that are only indirectly linked to intrinsic reward and often exert their influence outside awareness. Second-order conditioning (SOC) [1] is a basic associative-learning mechanism whereby stimuli acquire motivational salience by proxy, in the absence of primary incentives [2, 3]. Memory-systems theories consider first-order conditioning (FOC) and SOC to be prime examples of hippocampal-independent nondeclarative memory [4, 5]. Accordingly, neurobiological models of SOC focus almost exclusively on nondeclarative neural systems that support motivational salience and reward value. Transfer of value from a conditioned stimulus to a neutral stimulus is thought to require the basolateral amygdala [6, 7] and the ventral striatum [2, 3], but not the hippocampus. We developed a new paradigm to measure appetitive SOC of tones in rats. Hippocampal lesions severely impaired both acquisition and expression of SOC despite normal FOC. Unlike controls, rats with hippocampal lesions could not discriminate between positive and negative secondary conditioned tones, although they exhibited general familiarity with previously presented tones compared with new tones. Importantly, normal rats' behavior, in contrast to that of hippocampal groups, also revealed different confidence levels as indexed by effort, a central characteristic of hippocampal relational memory. The results indicate, contrary to current systems models, that representations of intrinsic relationships between reward value, stimulus identity, and motivation require hippocampal mediation when these relationships are of a higher order. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Clinical evaluation of dose-volume-effect relationship in radiation injury of the brain

    International Nuclear Information System (INIS)

    Saito, Mari

    1990-01-01

    Radiation brain injury, including functional disturbances or morphological changes (brain atrophy, periventricular lucencies or ventricular dilatation), were studied by CT in patients with primary intracranial neoplasms who were followed-up for at least 5 months after receiving radiotherapy. Each of 33 patients with medulloblastoma, pinealregion tumor or malignant lymphoma received a total dose of 40-61 Gy by conventional fractionation using a whole brain irradiation field boosted by a localized field. Of these patients, 19 (58%) developed radiation brain injury. It was concluded that the volume-dose was one of the most important factors influencing the development of radiation brain injury. Age at the time of radiotherapy and time of follow-up after the treatment were also considered to be important factors. (author)

  10. Intermediate levels of hippocampal activity appear optimal for associative memory formation.

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    Xiao Liu

    Full Text Available BACKGROUND: It is well established that hippocampal activity is positively related to effective associative memory formation. However, in biological systems often optimal levels of activity are contrasted by both sub- and supra-optimal levels. Sub-optimal levels of hippocampal activity are commonly attributed to unsuccessful memory formation, whereas the supra-optimal levels of hippocampal activity related to unsuccessful memory formation have been rarely studied. It is still unclear under what circumstances such supra-optimal levels of hippocampal activity occur. To clarify this issue, we aimed at creating a condition, in which supra-optimal hippocampal activity is associated with encoding failure. We assumed that such supra-optimal activity occurs when task-relevant information is embedded in task-irrelevant, distracting information, which can be considered as noise. METHODOLOGY/PRINCIPAL FINDINGS: In the present fMRI study, we probed neural correlates of associative memory formation in a full-factorial design with associative memory (subsequently remembered versus forgotten and noise (induced by high versus low distraction as factors. Results showed that encoding failure was associated with supra-optimal activity in the high-distraction condition and with sub-optimal activity in the low distraction condition. Thus, we revealed evidence for a bell-shape function relating hippocampal activity with associative encoding success. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that intermediate levels of hippocampal activity are optimal while both too low and too high levels appear detrimental for associative memory formation. Supra-optimal levels of hippocampal activity seem to occur when task-irrelevant information is added to task-relevant signal. If such task-irrelevant noise is reduced adequately, hippocampal activity is lower and thus optimal for associative memory formation.

  11. Morphological Variations of Hippocampal Formation in Epilepsy

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    J Gordon Millichap

    2013-02-01

    Full Text Available Researchers at Hospital Sao Paulo and other centers in Brazil compared the hippocampal formation (HF morphology of healthy asymptomatic individuals (n=30 with that of patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS(n=68, of patients with malformations of cortical development (MCD(n=34, and of patients with morphological HF variations without other structural signs (pure MVHF(n=12.

  12. Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

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    Eric J. Neuberger

    2017-09-01

    Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

  13. Hippocampal multimodal structural changes and subclinical depression in healthy individuals.

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    Spalletta, Gianfranco; Piras, Fabrizio; Caltagirone, Carlo; Fagioli, Sabrina

    2014-01-01

    Several neuroimaging studies report reduced hippocampal volume in depressed patients. However, it is still unclear if hippocampal changes in healthy individuals can be considered a risk factor for progression to clinical depression. Here, we investigated subclinical depression and its hippocampal correlates in a non-clinical sample of healthy individuals, with particular regard to gender differences. One-hundred-two participants underwent a comprehensive clinical assessment, a high-resolution T1-weighted magnetic resonance imaging and diffusion tensor imaging protocol using a 3T MRI scanner. Data of macro-(volume) and micro-(mean diffusivity, MD) structural changes of the hippocampus were analyzed with reference to the Beck Depression Inventory score. Results of multivariate regression analyses revealed reduced bilateral volume, along with increased bilateral MD in hippocampal formation predicting subclinical depressive phenomenology only in healthy males. Conversely, subclinical depressive phenomenology in healthy female was accounted for by only lower educational level, in the absence of any hippocampal structure variations. To date, this is the only evidence reporting a relationship between subclinical depressive phenomenology and changes in hippocampal formation in healthy individuals. Our findings demonstrated that reduced volume, along with increased MD in hippocampal formation, is significantly associated with subclinical depressive phenomenology in healthy males. This encourages to study the hypothesis that early macro- and microstructural changes in hippocampi associated with subclinical depression may constitute a risk factor of developing depressive disorders in males. © 2013 Elsevier B.V. All rights reserved.

  14. Memory impairment in multiple sclerosis: Relevance of hippocampal activation and hippocampal connectivity

    NARCIS (Netherlands)

    Hulst, H.E.; Schoonheim, M.M.; van Geest, Q.; Uitdehaag, B.M.J.; Barkhof, F.; Geurts, J.J.G.

    2015-01-01

    Background: Memory impairment is frequent in multiple sclerosis (MS), but it is unclear what functional brain changes underlie this cognitive deterioration. Objective: To investigate functional hippocampal activation and connectivity, in relation to memory performance in MS. Methods: Structural and

  15. Hypoxic ischemia encephalopathy leading to external hydrocephalus and the cerebral atrophy: mechanism and differential diagnosis

    International Nuclear Information System (INIS)

    Huang Zhenglin; Mo Xiaorong

    2002-01-01

    Objective: It is a study of the mechanism and differential diagnosis of the infant external hydrocephalus and cerebral atrophy. Methods: In total 84 cases of neonatal hypoxic ischemia encephalopathy followed by infant external hydrocephalus were investigated, among which 26 patients gradually were found having developed cerebral atrophy in follow up. Results: Characteristic dilation of the frontal-parietal subarachnoid space and the adjacent cistern was noted on the CT images of the external hydrocephalus. CT revealed the enlarged ventricle besides the dilated subarachnoid space in the cases of cerebral atrophy, while these two entities were indistinguishable on CT in the early stage. Conclusion: Clinical manifestations make a major differential diagnosis of the external hydrocephalus and cerebral atrophy: tic and mild delayed development of locomotion over major presentation of external hydrocephalus, while cerebral atrophy is featured by remarkable dysnoesia and severe delayed development of locomotion. In addition, hemiplegia and increased muscular tension are presented in a few cases of cerebral atrophy

  16. Progression of regional grey matter atrophy in multiple sclerosis.

    Science.gov (United States)

    Eshaghi, Arman; Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Prados, Ferran; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

    2018-06-01

    See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple

  17. Progression of regional grey matter atrophy in multiple sclerosis

    Science.gov (United States)

    Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

    2018-01-01

    Abstract See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article. Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse

  18. Significance of frontal cortical atrophy in Parkinson's disease: computed tomographic study

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    Lee, Kyung Sang; Suh, Jung Ho; Chung, Tae Sub; Kim, Dong Ik [College of Medicine, Yonsei University, Seoul (Korea, Republic of)

    1987-10-15

    Fifty-five patients with Parkinson's disease were evaluated clinically and with brain computed tomography (CT) in order to determine the incidence of frontal cortical and subcortical atrophy. Twenty cases of age-related healthy control group were also scanned. The CT criteria of frontal cortical atrophy that was used in this study were the maximum width of frontal hemispheric cortical sulci and width of anterior interhemispheric fissure between frontal lobes comparing with maximum width of hemispheric cortical sulci except frontal lobes. And the criteria of frontal subcortical atrophy were bifrontal index bicaudate index, and Evans index. The results are as follows: 1. Cortical atrophic changes in Parkinson's disease were more prominent in frontal lobe rather than other causes of cortical atrophy. 2. Frontal cortical and subcortical atrophic changes were also more prominent in Parkinson's disease rather than age-related control group. 3. Subcortical atrophic changes in frontal lobe were always associated with cortical atrophic changes. 4. Changes of basal ganglia were hardly seen in Parkinson's disease. 5. Cortical atrophic changes in frontal lobe must be the one of significant findings in Parkinson's disease.

  19. Significance of frontal cortical atrophy in Parkinson's disease: computed tomographic study

    International Nuclear Information System (INIS)

    Lee, Kyung Sang; Suh, Jung Ho; Chung, Tae Sub; Kim, Dong Ik

    1987-01-01

    Fifty-five patients with Parkinson's disease were evaluated clinically and with brain computed tomography (CT) in order to determine the incidence of frontal cortical and subcortical atrophy. Twenty cases of age-related healthy control group were also scanned. The CT criteria of frontal cortical atrophy that was used in this study were the maximum width of frontal hemispheric cortical sulci and width of anterior interhemispheric fissure between frontal lobes comparing with maximum width of hemispheric cortical sulci except frontal lobes. And the criteria of frontal subcortical atrophy were bifrontal index bicaudate index, and Evans index. The results are as follows: 1. Cortical atrophic changes in Parkinson's disease were more prominent in frontal lobe rather than other causes of cortical atrophy. 2. Frontal cortical and subcortical atrophic changes were also more prominent in Parkinson's disease rather than age-related control group. 3. Subcortical atrophic changes in frontal lobe were always associated with cortical atrophic changes. 4. Changes of basal ganglia were hardly seen in Parkinson's disease. 5. Cortical atrophic changes in frontal lobe must be the one of significant findings in Parkinson's disease

  20. Brain injury with diabetes mellitus: evidence, mechanisms and treatment implications.

    Science.gov (United States)

    Hamed, Sherifa A

    2017-04-01

    Diabetes mellitus is a risk for brain injury. Brain injury is associated with acute and chronic hyperglycaemia, insulin resistance, hyperinsulinemia, diabetic ketoacidosis (DKA) and hypoglycaemic events in diabetic patients. Hyperglycemia is a cause of cognitive deterioration, low intelligent quotient, neurodegeneration, brain aging, brain atrophy and dementia. Areas covered: The current review highlights the experimental, clinical, neuroimaging and neuropathological evidence of brain injury induced by diabetes and its associated metabolic derangements. It also highlights the mechanisms of diabetes-induced brain injury. It seems that the pathogenesis of hyperglycemia-induced brain injury is complex and includes combination of vascular disease, oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis, reduction of neurotrophic factors, acetylcholinesterase (AChE) activation, neurotransmitters' changes, impairment of brain repair processes, impairment of brain glymphatic system, accumulation of amyloid β and tau phosphorylation and neurodegeneration. The potentials for prevention and treatment are also discussed. Expert commentary: We summarize the risks and the possible mechanisms of DM-induced brain injury and recommend strategies for neuroprotection and neurorestoration. Recently, a number of drugs and substances [in addition to insulin and its mimics] have shown promising potentials against diabetes-induced brain injury. These include: antioxidants, neuroinflammation inhibitors, anti-apoptotics, neurotrophic factors, AChE inhibitors, mitochondrial function modifiers and cell based therapies.

  1. Calcified neurocysticercosis lesions and hippocampal sclerosis: potential dual pathology?

    Science.gov (United States)

    Rathore, Chaturbhuj; Thomas, Bejoy; Kesavadas, Chandrasekharan; Radhakrishnan, Kurupath

    2012-04-01

    In areas where cysticercosis is endemic, calcified neurocysticercosis lesion(s) (CNL) and hippocampal sclerosis (HS) commonly coexist in patients with localization-related epilepsies. To understand the pathogenesis of HS associated with CNL, we compared the characteristics of three groups of patients with antiepileptic drug-resistant epilepsies: CNL with HS, CNL without HS (CNL alone), and HS without CNL (HS alone). In comparison to patients with CNL alone, those with CNL with HS had CNL more frequently located in the ipsilateral temporal lobe. Those with CNL with HS had a lower incidence of febrile seizures, older age at initial precipitating injury and at onset of habitual complex partial seizures, and more frequent clustering of seizures and extratemporal/bitemporal interictal epileptiform discharges as compared to patients with HS alone. Our study illustrates that HS associated with CNL might have a different pathophysiologic basis as compared to classical HS. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  2. Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

    Science.gov (United States)

    Kalyan-Masih, Priya; Vega-Torres, Julio David; Haddad, Elizabeth; Rainsbury, Sabrina; Baghchechi, Mohsen

    2016-01-01

    Abstract Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to post-traumatic stress responsivity. Adolescent Lewis rats (postnatal day 28) were fed ad libitum for 8 weeks with either the experimental WD diet (41.4% kcal from fat) or the control diet (16.5% kcal from fat). We modeled psychological trauma by exposing young adult rats to a cat odor threat. The elevated plus maze and the open field test revealed increased psychological trauma-induced anxiety-like behaviors in the rats that consumed the WD when compared with control animals 1 week after undergoing traumatic stress (p < 0.05). Magnetic resonance imaging showed significant hippocampal atrophy (20% reduction) and lateral ventricular enlargement (50% increase) in the animals fed the WD when compared with controls. These volumetric abnormalities were associated with behavioral indices of anxiety, increased leptin and FK506-binding protein 51 (FKBP51) levels, and reduced hippocampal blood vessel density. We found asymmetric structural vulnerabilities to the WD, particularly the ventral and left hippocampus and lateral ventricle. This study highlights how WD consumption during adolescence impacts key substrates implicated in post-traumatic stress disorder. Understanding how consumption of a WD affects the developmental trajectories of the stress neurocircuitry is critical, as stress susceptibility imposes a marked vulnerability to neuropsychiatric disorders. PMID:27844058

  3. Molecular events underlying skeletal muscle atrophy and the development of effective countermeasures

    Science.gov (United States)

    Booth, F. W.; Criswell, D. S.

    1997-01-01

    Skeletal muscle adapts to loading; atrophying when exposed to unloading on Earth or in spaceflight. Significant atrophy (decreases in muscle fiber cross-section of 11-24%) in humans has been noted after only 5 days in space. Since muscle strength is determined both by muscle cross-section and synchronization of motor unit recruitment, a loss in muscle size weakens astronauts, which would increase risks to their safety if an emergency required maximal muscle force. Numerous countermeasures have been tested to prevent atrophy. Resistant exercise together with growth hormone and IGF-I are effective countermeasures to unloading as most atrophy is prevented in animal models. The loss of muscle protein is due to an early decrease in protein synthesis rate and a later increase in protein degradation. The initial decrease in protein synthesis is a result of decreased protein translation, caused by a prolongation in the elongation rate. A decrease in HSP70 by a sight increase in ATP may be the factors prolonging elongation rate. Increases in the activities of proteolytic enzymes and in ubiquitin contribute to the increased protein degradation rate in unloaded muscle. Numerous mRNA concentrations have been shown to be altered in unloaded muscles. Decreases in mRNAs for contractile proteins usually occur after the initial fall in protein synthesis rates. Much additional research is needed to determine the mechanism by which muscle senses the absence of gravity with an adaptive atrophy. The development of effective countermeasures to unloading atrophy will require more research.

  4. Proximal spinal muscular atrophy: current orthopedic perspective

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    Haaker G

    2013-11-01

    Full Text Available Gerrit Haaker, Albert Fujak Department of Orthopaedic Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany Abstract: Spinal muscular atrophy (SMA is a hereditary neuromuscular disease of lower motor neurons that is caused by a defective "survival motor neuron" (SMN protein that is mainly associated with proximal progressive muscle weakness and atrophy. Although SMA involves a wide range of disease severity and a high mortality and morbidity rate, recent advances in multidisciplinary supportive care have enhanced quality of life and life expectancy. Active research for possible treatment options has become possible since the disease-causing gene defect was identified in 1995. Nevertheless, a causal therapy is not available at present, and therapeutic management of SMA remains challenging; the prolonged survival is increasing, especially orthopedic, respiratory and nutritive problems. This review focuses on orthopedic management of the disease, with discussion of key aspects that include scoliosis, muscular contractures, hip joint disorders, fractures, technical devices, and a comparative approach of conservative and surgical treatment. Also emphasized are associated complications including respiratory involvement, perioperative care and anesthesia, nutrition problems, and rehabilitation. The SMA disease course can be greatly improved with adequate therapy with established orthopedic procedures in a multidisciplinary therapeutic approach. Keywords: spinal muscular atrophy, scoliosis, contractures, fractures, lung function, treatment, rehabilitation, surgery, ventilation, nutrition, perioperative management

  5. Evaluation of supra- and infratentorial brain atrophy by computerized tomography in spinocerebellar degeneration

    International Nuclear Information System (INIS)

    Yamamoto, Hiroko; Asano, Yasuhiko; Watanabe, Takatoshi; Hirao, Yoshitaka; Mizuno, Yasushi; Sobue, Itsuro

    1986-01-01

    Measurement of various parameters of supra- and infratentorial brain atrophy in computerized tomographs of 142 cases of spinocerebellar degeneration (SCD) and 100 age and sex matched controls was carried out in order to investigate whether these parameters would correspond to the subtypes of this disease and differing grades of various clinical manifestations. One supra- and all infratentorial parameters of SCD showed statistically significant atrophy with a risk of P < 0.005. Among the subtypes, OPCA had a more severely atrophied pons than LCCA (P < 0.005), Menzel (P < 0.05) and SSP (P < 0.01). There was a correlation between the distribution of symptoms like gait, speech, ataxia of extremities and ocular movement disorders, and distribution and degree of infratentorial atrophy with statistical significance (P < 0.05 ∼ P < 0.005). The degree of atrophy of the pons and the width of the IV ventricle were directly proportional to the duration of the illness in cases of less than 10 years, but not to those of over 10 years. Follow-up CT scan was done for 24 patients, 12 within 3 years, 12 after the lapse of 3 years. The latter group showed statistically significant atrophy between the 1st and 2nd scans in several parameters, but there was no significance between those of the former group. (author)

  6. Evaluation of supra- and infratentorial brain atrophy by computerized tomography in spinocerebellar degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Hiroko; Asano, Yasuhiko; Watanabe, Takatoshi; Hirao, Yoshitaka; Mizuno, Yasushi; Sobue, Itsuro

    1986-08-01

    Measurement of various parameters of supra- and infratentorial brain atrophy in computerized tomographs of 142 cases of spinocerebellar degeneration (SCD) and 100 age and sex matched controls was carried out in order to investigate whether these parameters would correspond to the subtypes of this disease and differing grades of various clinical manifestations. One supra- and all infratentorial parameters of SCD showed statistically significant atrophy with a risk of P < 0.005. Among the subtypes, OPCA had a more severely atrophied pons than LCCA (P < 0.005), Menzel (P < 0.05) and SSP (P < 0.01). There was a correlation between the distribution of symptoms like gait, speech, ataxia of extremities and ocular movement disorders, and distribution and degree of infratentorial atrophy with statistical significance (P < 0.05 -- P < 0.005). The degree of atrophy of the pons and the width of the IV ventricle were directly proportional to the duration of the illness in cases of less than 10 years, but not to those of over 10 years. Follow-up CT scan was done for 24 patients, 12 within 3 years, 12 after the lapse of 3 years. The latter group showed statistically significant atrophy between the 1st and 2nd scans in several parameters, but there was no significance between those of the former group.

  7. Parry-Romberg syndrome (progressive hemifacial atrophy) with spasmodic dysphonia--a rare association.

    Science.gov (United States)

    Mugundhan, K; Selvakumar, C J; Gunasekaran, K; Thiruvarutchelvan, K; Sivakumar, S; Anguraj, M; Arun, S

    2014-04-01

    Parry-Romberg syndrome is a rare clinical entity characterised by progressive hemifacial atrophy with appearance of 'saber'. Various neurological and otorhinolaryngological disorders are associated with this syndrome. The association of Parry -Romberg syndrome with Spasmodic dysphonia has rarely been reported. A 37 year old female presented with progressive atrophy of tissues of left side of face for 10 years and change in voice for 1 year. On examination, wasting and atrophy of tissues including tongue was noted on left side of the face. ENT examination revealed adductor spasmodic dysphonia. We report the rare association of Parry -Romberg syndrome with spasmodic dysphonia.

  8. Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease

    International Nuclear Information System (INIS)

    Kanoto, Masafumi; Hosoya, Takaaki; Toyoguchi, Yuuki; Oda, Atsuko

    2013-01-01

    Purpose: Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. Materials and methods: The subjects consist of a CPNBD group (n = 4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n = 19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n = 23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Results: Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p < 0.05), and between the CPNBD group and the normal control group (p < 0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p < 0.001, p < 0.01 respectively), and between the CPNBD group and the normal control group (p < 0.001). Conclusions: Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis

  9. Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma

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    Xiaodong Mu

    2016-01-01

    Full Text Available Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy. In vitro coculture of osteosarcoma cells with muscle-derived stem cells (MDSCs isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia.

  10. Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1.

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    Meng-Chuan Chen

    Full Text Available Skeletal muscle atrophy, the most prominent phenotypic feature of cancer cachexia, is often observed in cancer patients undergoing chemotherapy. Magnolol (M extracted from Magnolia officinalis exhibits several pharmacological effects including anti-inflammatory and anticancer activities. In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM or gemcitabine (TGM, markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC. The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1 production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis.

  11. PirB regulates asymmetries in hippocampal circuitry.

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    Hikari Ukai

    Full Text Available Left-right asymmetry is a fundamental feature of higher-order brain structure; however, the molecular basis of brain asymmetry remains unclear. We recently identified structural and functional asymmetries in mouse hippocampal circuitry that result from the asymmetrical distribution of two distinct populations of pyramidal cell synapses that differ in the density of the NMDA receptor subunit GluRε2 (also known as NR2B, GRIN2B or GluN2B. By examining the synaptic distribution of ε2 subunits, we previously found that β2-microglobulin-deficient mice, which lack cell surface expression of the vast majority of major histocompatibility complex class I (MHCI proteins, do not exhibit circuit asymmetry. In the present study, we conducted electrophysiological and anatomical analyses on the hippocampal circuitry of mice with a knockout of the paired immunoglobulin-like receptor B (PirB, an MHCI receptor. As in β2-microglobulin-deficient mice, the PirB-deficient hippocampus lacked circuit asymmetries. This finding that MHCI loss-of-function mice and PirB knockout mice have identical phenotypes suggests that MHCI signals that produce hippocampal asymmetries are transduced through PirB. Our results provide evidence for a critical role of the MHCI/PirB signaling system in the generation of asymmetries in hippocampal circuitry.

  12. Taurine Rescues Cisplatin-Induced Muscle Atrophy In Vitro: A Morphological Study

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    Alessandra Stacchiotti

    2014-01-01

    Full Text Available Cisplatin (CisPt is a widely used chemotherapeutic drug whose side effects include muscle weakness and cachexia. Here we analysed CisPt-induced atrophy in C2C12 myotubes by a multidisciplinary morphological approach, focusing on the onset and progression of autophagy, a protective cellular process that, when excessively activated, may trigger protein hypercatabolism and atrophy in skeletal muscle. To visualize autophagy we used confocal and transmission electron microscopy at different times of treatment and doses of CisPt. Moreover we evaluated the effects of taurine, a cytoprotective beta-amino acid able to counteract oxidative stress, apoptosis, and endoplasmic reticulum stress in different tissues and organs. Our microscopic results indicate that autophagy occurs very early in 50 μM CisPt challenged myotubes (4 h–8 h before overt atrophy but it persists even at 24 h, when several autophagic vesicles, damaged mitochondria, and sarcoplasmic blebbings engulf the sarcoplasm. Differently, 25 mM taurine pretreatment rescues the majority of myotubes size upon 50 μM CisPt at 24 h. Taurine appears to counteract atrophy by restoring regular microtubular apparatus and mitochondria and reducing the overload and the localization of autophagolysosomes. Such a promising taurine action in preventing atrophy needs further molecular and biochemical studies to best define its impact on muscle homeostasis and the maintenance of an adequate skeletal mass in vivo.

  13. Caffeine Increases Hippocampal Sharp Waves in Vitro.

    Science.gov (United States)

    Watanabe, Yusuke; Ikegaya, Yuji

    2017-01-01

    Caffeine promotes memory consolidation. Memory consolidation is thought to depend at least in part on hippocampal sharp waves (SWs). In the present study, we investigated the effect of bath-application of caffeine in spontaneously occurring SWs in mouse acute hippocampal slices. Caffeine induced an about 100% increase in the event frequency of SWs at concentrations of 60 and 200 µM. The effect of caffeine was reversible after washout of caffeine and was mimicked by an adenosine A 1 receptor antagonist, but not by an A 2A receptor antagonist. Caffeine increased SWs even in dentate-CA3 mini-slices without the CA2 regions, in which adenosine A 1 receptors are abundantly expressed in the hippocampus. Thus, caffeine facilitates SWs by inhibiting adenosine A 1 receptors in the hippocampal CA3 region or the dentate gyrus.

  14. Assessment of vaginal atrophy: a review

    NARCIS (Netherlands)

    Weber, M. A.; Limpens, J.; Roovers, J. P. W. R.

    2015-01-01

    The aim of this study is to provide an evidence-based definition of vaginal atrophy (VA) and present an overview of subjective and objective measurements of VA applicable in clinical practice and research. A systematic literature search was performed in MEDLINE and EMBASE to identify studies

  15. Association between anti-endomysial antibody and total intestinal villous atrophy in children with coeliac disease.

    Directory of Open Access Journals (Sweden)

    Ozgenc F

    2003-01-01

    Full Text Available BACKGROUND: There is growing evidence to suggest that detection of anti-gliadin antibody (AGA and anti-endomysial antibody (EmA can serve as sensitive markers of the degree of histological abnormalities in patients with coeliac disease. AIM: To evaluate the association between the presence of AGA and EmA and villous atrophy in intestinal biopsies of children with suspected coeliac disease. SETTINGS AND DESIGN: Intestinal samples of 46 children with failure to thrive, chronic diarrhoea, malabsorption and short stature with either AGA and/or EmA positivity were evaluated, retrospectively. The diagnosis of coeliac disease was based on ESPGHAN criteria. METHODS AND MATERIAL: Patients with total villous atrophy who fulfilled the ESPGHAN criteria for the diagnosis of coeliac disease were diagnosed to have coeliac disease. Nine patients without villous atrophy were taken as negative controls for this study. AGA-IgA was measured both by immunoflourescence (IF and ELISA and EmA-IgA by IF while patients were on normal diet. Relationship between autoantibody positivity and intestinal total villous atrophy was evaluated. RESULTS: Overall positivity for AGA IgA was 85% (39/46 by IF+ELISA and EmA positivity was 85% (39/46 by IF within the study group. Histological examination revealed total villous atrophy with lymphocyte infiltration and crypt hyperplasia in 37 (80% patients. AGA IgA was positive in 14 (38% and 31 (84% of these children by ELISA and IF, respectively. EmA positivity was detected in 35/37 (95% cases with atrophy and 4/9 (44% without atrophy (p=0.002. Thirty out of 37 (81% patients with villous atrophy had both AGA IgA (IF and EmA positivity (p=0.186. All of the sixteen patients that had both positive AGA IgA (ELISA+IF and EmA had total villous atrophy (p=0.037. CONCLUSION: A significant association between total villous atrophy and EmA positivity has been documented in this study.

  16. Correlation between volume and morphological changes in the hippocampal formation in Alzheimer's disease: rounding of the outline of the hippocampal body on coronal MR images

    International Nuclear Information System (INIS)

    Adachi, Michito; Sato, Takamichi; Kawakatsu, Shinobu; Ohshima, Fumi

    2012-01-01

    The aim of this study was to investigate whether the outline of the hippocampal body becomes rounded on coronal magnetic resonance imaging (MRI) as the volume of the hippocampal formation decreases in Alzheimer's disease (AD). Institutional review board approval of the study protocol was obtained, and all subjects provided informed consent for the mini-mental state examination (MMSE) and MRI. The MRI and MMSE were prospectively performed in all 103 subjects (27 men and 76 women; mean age ± standard deviation, 77.7 ± 7.8 years) who had AD or were concerned about having of dementia and who consulted our institute over 1 year. The subjects included 14 non-dementia cases (MMSE score ≥ 28) and 89 AD cases (MMSE score ≤ 27). The total volume of the bilateral hippocampal formation (VHF) was assessed with a tracing method, and the ratio of the VHF to the intracranial volume (RVHF) and the rounding ratio (RR) of the hippocampal body (mean ratio of its short dimension to the long dimension in the bilateral hippocampal body) were calculated. Using Spearman's correlation coefficient, the correlations between RR and VHF and between RR and RVHF were assessed. Correlation coefficients between RR and VHF and between RR and RVHF were -0.419 (p < 0.01) and -0.418 (p < 0.01), respectively. There was a significant negative correlation between RR and the volume of the hippocampal formation. The outline of the body of the hippocampal formation becomes rounded on coronal images as its volume decreases in AD. (orig.)

  17. Prominent microglial activation in cortical white matter is selectively associated with cortical atrophy in primary progressive aphasia.

    Science.gov (United States)

    Ohm, Daniel T; Kim, Garam; Gefen, Tamar; Rademaker, Alfred; Weintraub, Sandra; Bigio, Eileen; Mesulam, M-Marsel; Rogalski, Emily; Geula, Changiz

    2018-04-21

    Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy are unknown. We investigated white matter activated microglia and their association with grey matter atrophy in 10 PPA cases with either AD or FTLD-TDP pathology. Activated microglia were quantified with optical density measures of HLA-DR immunoreactivity in two regions with peak cortical atrophy, and one non-atrophied region within the language dominant hemisphere of each PPA case. Non-atrophied contralateral homologues of the language dominant regions were examined for hemispheric asymmetry. Qualitatively, greater densities of activated microglia were observed in cortical white matter when compared to grey matter. Quantitative analyses revealed significantly greater densities of activated microglia in the white matter of atrophied regions compared to non-atrophied regions in the language dominant hemisphere (p<0.05). Atrophied regions of the language dominant hemisphere also showed significantly more activated microglia compared to contralateral homologues (p<0.05). White matter activated microglia accumulate more in atrophied regions in the language dominant hemisphere of PPA. While microglial activation may constitute a response to neurodegenerative processes in white matter, the resultant inflammatory processes may also exacerbate disease progression and contribute to cortical atrophy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Depression, depressive symptoms, and rate of hippocampal atrophy in a longitudinal cohort of older men and women.

    Science.gov (United States)

    Elbejjani, M; Fuhrer, R; Abrahamowicz, M; Mazoyer, B; Crivello, F; Tzourio, C; Dufouil, C

    2015-07-01

    Several studies have reported smaller hippocampal volume (HcV) in depression patients; however, the temporality of the association remains unknown. One proposed hypothesis is that depression may cause HcV loss. This study evaluates whether previous depression and recent depressive symptoms are associated with HcV and HcV loss. We used a prospective cohort of older adults (n = 1328; age = 65-80 years) with two cerebral magnetic resonance imaging examinations at baseline and 4-year follow-up. Using multivariable linear regression models, we estimated, in stratified analyses by gender, the association between indicators of history of depression and its severity (age at onset, recurrence, hospitalization for depression), proximal depressive symptoms [Center for Epidemiologic Studies-Depression (CES-D) scale], baseline antidepressant use, and the outcomes: baseline HcV and annual percentage change in HcV. At baseline, women with more depressive symptoms had smaller HcV [-0.05 cm3, 95% confidence interval (CI) -0.1 to -0.01 cm3 per 10-unit increase in CES-D scores]. History of depression was associated with a 0.2% faster annual HcV loss in women (95% CI 0.01-0.36%). More baseline depressive symptoms and worsening of these symptoms were also associated with accelerated HcV loss in women. No associations were observed in men. Treatment for depression was associated with slower HcV loss in women and men. While only concomitant depressive symptoms were associated with HcV, both previous depression and more proximal depressive symptoms were associated with faster HcV loss in women.

  19. A Possible Link between Gastric Mucosal Atrophy and Gastric Cancer after Helicobacter pylori Eradication.

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    Tomomitsu Tahara

    Full Text Available The effect of H. pylori eradication in gastric cancer prevention can be attributed to the improvement of atrophic gastritis, which is a known risk of gastric cancer. However, gastric cancer has also been diagnosed after long-term H. pylori eradication. This study aimed to clarify the association between gastric atrophy and gastric cancer after H. pylori eradication, including its clinicopathological features.A total of 55 consecutive patients with 64 early gastric cancers (EGCs diagnosed after H. pylori eradication were enrolled. The degree of endoscopic atrophy and the histological degrees of mononuclear cell infiltration, atrophy, and metaplasia in the corpus and adjacent mucosa of the EGCs were determined and scored.The majority of EGCs (63/64 were located within the endoscopically assessed atrophic mucosa or along the atrophic border. The adjacent mucosa of the EGCs presented significantly higher degrees of all histological parameters than in the corpus (mononuclear cell infiltration, 0.86+/-0.09 vs. 0.51+/-0.11, P = 0.016; atrophy, 1.77+/-0.13 vs. 0.65+/-0.14, P<0.0001; metaplasia, 1.68+/-0.13 vs. 0.48+/-0.1, P<0.0001. The degree of endoscopic atrophy improved in the patients with longer post-H. pylori eradication periods; however, this trend was not observed for the histological parameters, and high degrees of atrophy and metaplasia were observed in the adjacent mucosa of the EGCs compared with the corpus during all periods (all P<0.05. The histological degrees of atrophy and metaplasia in the adjacent mucosa were particularly higher in the patients who underwent eradication due to gastric ulcers.Severe gastric atrophy remained in the adjacent mucosa of the EGCs after H. pylori eradication, which may be linked to gastric carcinogenesis.

  20. The PPARα Agonist Fenofibrate Preserves Hippocampal Neurogenesis and Inhibits Microglial Activation After Whole-Brain Irradiation

    International Nuclear Information System (INIS)

    Ramanan, Sriram; Kooshki, Mitra; Zhao Weiling; Hsu, F.-C.; Riddle, David R.; Robbins, Mike E.

    2009-01-01

    Purpose: Whole-brain irradiation (WBI) leads to cognitive impairment months to years after radiation. Numerous studies suggest that decreased hippocampal neurogenesis and microglial activation are involved in the pathogenesis of WBI-induced brain injury. The goal of this study was to investigate whether administration of the peroxisomal proliferator-activated receptor (PPAR) α agonist fenofibrate would prevent the detrimental effect of WBI on hippocampal neurogenesis. Methods and Materials: For this study, 129S1/SvImJ wild-type and PPARα knockout mice that were fed either regular or 0.2% wt/wt fenofibrate-containing chow received either sham irradiation or WBI (10-Gy single dose of 137 Cs γ-rays). Mice were injected intraperitoneally with bromodeoxyuridine to label the surviving cells at 1 month after WBI, and the newborn neurons were counted at 2 months after WBI by use of bromodeoxyuridine/neuronal nuclei double immunofluorescence. Proliferation in the subgranular zone and microglial activation were measured at 1 week and 2 months after WBI by use of Ki-67 and CD68 immunohistochemistry, respectively. Results: Whole-brain irradiation led to a significant decrease in the number of newborn hippocampal neurons 2 months after it was performed. Fenofibrate prevented this decrease by promoting the survival of newborn cells in the dentate gyrus. In addition, fenofibrate treatment was associated with decreased microglial activation in the dentate gyrus after WBI. The neuroprotective effects of fenofibrate were abolished in the knockout mice, indicating a PPARα-dependent mechanism or mechanisms. Conclusions: These data highlight a novel role for PPARα ligands in improving neurogenesis after WBI and offer the promise of improving the quality of life for brain cancer patients receiving radiotherapy.

  1. Carbocalcitonin treatment in Sudeck's atrophy

    International Nuclear Information System (INIS)

    Nuti, R.; Vattimo, A.; Martini, G.; Turchetti, V.; Righi, G.A.

    1987-01-01

    The efficacy of new calcitonin, the amino analog of eel calcitonin (carboCT) on Sudeck's atrophy of the foot was investigated in 14 patients. CarboCT was administered at the dose of 40 Medical Research Council (MRC) units per day, and the duration of treatment was two to ten months. No adverse effects were noted. Bone pain and local edema decreased associated with improvement of motility. CarboCT induced a slight decrease in plasma calcium, plasma phosphate, and 24-hour urinary calcium excretion. An increase in cAMP/Cr ratio, an index of parathyroid function, was also observed (probably a manifestation of the hypocalcemic effect of calcitonin and secondary parathyroid stimulation). The whole body retention of 99mTc-MDP represents a valuable index of bone turnover, it decreased progressively and significantly on treatment. A dynamic study of local bone uptake of 99mTC-MDP was performed in eight patients. After carboCT therapy, statistically significant decreases in local blood flow, early uptake, and delayed uptake were appreciated in the involved foot. These findings lead to the conclusion that carboCT is effective in the treatment of Sudeck's atrophy

  2. Carbocalcitonin treatment in Sudeck's atrophy.

    Science.gov (United States)

    Nuti, R; Vattimo, A; Martini, G; Turchetti, V; Righi, G A

    1987-02-01

    The efficacy of new calcitonin, the amino analog of eel calcitonin (carboCT) on Sudeck's atrophy of the foot was investigated in 14 patients. CarboCT was administered at the dose of 40 Medical Research Council (MRC) units per day, and the duration of treatment was two to ten months. No adverse effects were noted. Bone pain and local edema decreased associated with improvement of motility. CarboCT induced a slight decrease in plasma calcium, plasma phosphate, and 24-hour urinary calcium excretion. An increase in cAMP/Cr ratio, an index of parathyroid function, was also observed (probably a manifestation of the hypocalcemic effect of calcitonin and secondary parathyroid stimulation). The whole body retention of 99mTc-MDP represents a valuable index of bone turnover, it decreased progressively and significantly on treatment. A dynamic study of local bone uptake of 99mTC-MDP was performed in eight patients. After carboCT therapy, statistically significant decreases in local blood flow, early uptake, and delayed uptake were appreciated in the involved foot. These findings lead to the conclusion that carboCT is effective in the treatment of Sudeck's atrophy.

  3. Spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Lieberman, Andrew P

    2018-01-01

    Spinal and bulbar muscular atrophy (SBMA) is an adult-onset degenerative disorder of the neuromuscular system resulting in slowly progressive weakness and atrophy of the proximal limb and bulbar muscles. The disease is caused by the expansion of a CAG/glutamine tract in the amino-terminus of the androgen receptor. That SBMA exclusively affects males reflects the fact that critical pathogenic events are hormone-dependent. These include translocation of the polyglutamine androgen receptor from the cytoplasm to the nucleus and unfolding of the mutant protein. Studies of the pathology of SBMA subjects have revealed nuclear aggregates of the mutant androgen receptor, loss of lower motor neurons in the brainstem and spinal cord, and both neurogenic and myopathic changes in skeletal muscle. Mechanisms underlying disease pathogenesis include toxicity in both lower motor neurons and skeletal muscle, where effects on transcription, intracellular transport, and mitochondrial function have been documented. Therapies to treat SBMA patients remain largely supportive, although experimental approaches targeting androgen action or promoting degradation of the mutant androgen receptor protein or the encoding RNA are under active study. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Qualitative and Quantitative Hippocampal MRI Assessments in Intractable Epilepsy

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    Paramdeep Singh

    2013-01-01

    Full Text Available Aims. To acquire normative data of hippocampal volumes and T2 relaxation times, to evaluate and compare qualitative and quantitative assessments in evaluating hippocampi in patients with different durations of intractable epilepsy, and to propose an imaging protocol based on performance of these techniques. Methods. MRI analysis was done in 50 nonepileptic controls and 30 patients with intractable epilepsy on 1.5T scanner. Visual assessment and hippocampal volumetry were done on oblique coronal IR/T2W and T1W MP-RAGE images, respectively. T2 relaxation times were measured using 16-echo Carr-Purcell-Meiboom-Gill sequence. Volumetric data was normalized for variation in head size between individuals. Patients were divided into temporal ( and extratemporal ( groups based on clinical and EEG localization. Results. In controls, right hippocampal volume was slightly more than the left with no effect of age or gender. In TLE patients, hippocampal volumetry provided maximum concordance with EEG. Visual assessment of unilateral pathology concurred well with measured quantitative values but poorly in cases with bilateral pathologies. There were no significant differences of mean values between extratemporal group and controls group. Quantitative techniques detected mild abnormalities, undetected on visual assessment. Conclusions. Quantitative techniques are more sensitive to diagnose bilateral and mild unilateral hippocampal abnormalities.

  5. Spatiotemporal Propagation of the Cortical Atrophy: Population and Individual Patterns

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    Igor Koval

    2018-05-01

    Full Text Available Repeated failures in clinical trials for Alzheimer’s disease (AD have raised a strong interest for the prodromal phase of the disease. A better understanding of the brain alterations during this early phase is crucial to diagnose patients sooner, to estimate an accurate disease stage, and to give a reliable prognosis. According to recent evidence, structural alterations in the brain are likely to be sensitive markers of the disease progression. Neuronal loss translates in specific spatiotemporal patterns of cortical atrophy, starting in the enthorinal cortex and spreading over other cortical regions according to specific propagation pathways. We developed a digital model of the cortical atrophy in the left hemisphere from prodromal to diseased phases, which is built on the temporal alignment and combination of several short-term observation data to reconstruct the long-term history of the disease. The model not only provides a description of the spatiotemporal patterns of cortical atrophy at the group level but also shows the variability of these patterns at the individual level in terms of difference in propagation pathways, speed of propagation, and age at propagation onset. Longitudinal MRI datasets of patients with mild cognitive impairments who converted to AD are used to reconstruct the cortical atrophy propagation across all disease stages. Each observation is considered as a signal spatially distributed on a network, such as the cortical mesh, each cortex location being associated to a node. We consider how the temporal profile of the signal varies across the network nodes. We introduce a statistical mixed-effect model to describe the evolution of the cortex alterations. To ensure a spatiotemporal smooth propagation of the alterations, we introduce a constrain on the propagation signal in the model such that neighboring nodes have similar profiles of the signal changes. Our generative model enables the reconstruction of personalized

  6. Intellectual enrichment lessens the effect of brain atrophy on learning and memory in multiple sclerosis.

    Science.gov (United States)

    Sumowski, James F; Wylie, Glenn R; Chiaravalloti, Nancy; DeLuca, John

    2010-06-15

    Learning and memory impairments are prevalent among persons with multiple sclerosis (MS); however, such deficits are only weakly associated with MS disease severity (brain atrophy). The cognitive reserve hypothesis states that greater lifetime intellectual enrichment lessens the negative impact of brain disease on cognition, thereby helping to explain the incomplete relationship between brain disease and cognitive status in neurologic populations. The literature on cognitive reserve has focused mainly on Alzheimer disease. The current research examines whether greater intellectual enrichment lessens the negative effect of brain atrophy on learning and memory in patients with MS. Forty-four persons with MS completed neuropsychological measures of verbal learning and memory, and a vocabulary-based estimate of lifetime intellectual enrichment. Brain atrophy was estimated with third ventricle width measured from 3-T magnetization-prepared rapid gradient echo MRIs. Hierarchical regression was used to predict learning and memory with brain atrophy, intellectual enrichment, and the interaction between brain atrophy and intellectual enrichment. Brain atrophy predicted worse learning and memory, and intellectual enrichment predicted better learning; however, these effects were moderated by interactions between brain atrophy and intellectual enrichment. Specifically, higher intellectual enrichment lessened the negative impact of brain atrophy on both learning and memory. These findings help to explain the incomplete relationship between multiple sclerosis disease severity and cognition, as the effect of disease on cognition is attenuated among patients with higher intellectual enrichment. As such, intellectual enrichment is supported as a protective factor against disease-related cognitive impairment in persons with multiple sclerosis.

  7. Neuropsychiatric disorders and cognitive dysfunction in patients with Cushing's disease.

    Science.gov (United States)

    Chen, Yu-fan; Li, Yun-feng; Chen, Xiao; Sun, Qing-fang

    2013-08-01

    To review the main neuropsychiatric disorders and cognitive deficits in patients with Cushing's disease (CD) and the associated pathophysiological mechanisms underlying CD. These mechanistic details may provide recommendations for preventing or treating the cognitive impairments and mood disorders in patients with CD. Data were obtained from papers on psychiatric and cognitive complications in CD published in English within the last 20 years. To perform the PubMed literature search, the following keywords were input: cushing's disease, cognitive, hippocampal, or glucocorticoids. Studies were selected if they contained data relevant to the topic addressed in the particular section. Because of the limited length of this article, we have frequently referenced recent reviews that contain a comprehensive amalgamation of literature rather than the actual source papers. Patients with active CD not only suffer from many characteristic clinical features, but also show some neuropsychiatric disorders and cognitive impairments. Among the psychiatric manifestations, the common ones are emotional instability, depressive disorder, anxious symptoms, impulsivity, and cognitive impairment. Irreversible effects of previous glucocorticoid (GC) excess on the central nervous system, such as hippocampal and the basal ganglia, is the most reasonable reason. Excess secretion of cortisol brings much structural and functional changes in hippocampal, such as changes in neurogenesis and morphology, signaling pathway, gene expression, and glutamate accumulation. Hippocampal volume loss can be found in most patients with CD, and decreased glucose utilization caused by GCs may lead to brain atrophy, neurogenesis impairment, inhibition of long-term potentiation, and decreased neurotrophic factors; these may also explain the mechanisms of GC-induced brain atrophy and hippocampal changes. Brain atrophy and hippocampal changes caused by excess secretion of cortisol are thought to play a significant

  8. Extensive immune-mediated hippocampal damage in mice surviving infection with neuroadapted Sindbis virus

    International Nuclear Information System (INIS)

    Kimura, Takashi; Griffin, Diane E.

    2003-01-01

    Viral infections of the central nervous system and immune responses to these infections cause a variety of neurological diseases. Infection of weanling mice with Sindbis virus causes acute nonfatal encephalomyelitis followed by clearance of infectious virus, but persistence of viral RNA. Infection with a neuroadapted strain of Sindbis virus (NSV) causes fatal encephalomyelitis, but passive transfer of immune serum after infection protects from fatal disease and infectious virus is cleared. To determine whether persistent NSV RNA is associated with neurological damage, we examined the brains of recovered mice and found progressive loss of the hippocampal gyrus, adjacent white matter, and deep cerebral cortex associated with mononuclear cell infiltration. Mice deficient in CD4 + T cells showed less tissue loss, while mice lacking CD8 + T cells showed lesions comparable to those in immunocompetent mice. Mice deficient in both CD4 + and CD8 + T cells developed severe tissue loss similar to immunocompetent mice and this was associated with extensive infiltration of macrophages. The number of CD4 + cells and macrophage/microglial cells, but not CD8 + cells, infiltrating the hippocampal gyrus was correlated with the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling positive pyramidal neurons. These results suggest that CD4 + T cells can promote progressive neuronal death and tissue injury, despite clearance of infectious virus

  9. Duodenal Villous Atrophy in a TTG-Negative Patient Taking Olmesartan: A Case Report and Review of the Literature

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    Tasha Kulai

    2016-01-01

    Full Text Available Olmesartan, an angiotensin II receptor antagonist used to treat hypertension, is associated with few adverse effects. Here, a case of severe sprue-like enteropathy and acute kidney injury is described in a 68-year-old male taking olmesartan for 3-4 years. He presented to hospital with a five-week history of diarrhea, vomiting, and a 20 lb weight loss. Anti-TTG was negative with a normal IgA. Biopsies of the distal duodenum and duodenal cap revealed marked blunting of the villi with near complete villous atrophy of the biopsies from the bulb. There was an increase in intraepithelial lymphocytes as well as neutrophils in the surface epithelium. The patient’s diarrhea improved upon discontinuation of olmesartan and he returned to his previous weight. Repeat endoscopy four months later demonstrated complete resolution of inflammatory change with normal villous architecture. Long-term olmesartan use is associated with severe sprue-like enteropathy. The mechanism of intestinal injury is unknown. Duodenal biopsy results may mimic other enteropathies such as celiac disease. Physicians should consider medications as potential etiologies of enteropathy.

  10. Hippocampal Structure Predicts Statistical Learning and Associative Inference Abilities during Development.

    Science.gov (United States)

    Schlichting, Margaret L; Guarino, Katharine F; Schapiro, Anna C; Turk-Browne, Nicholas B; Preston, Alison R

    2017-01-01

    Despite the importance of learning and remembering across the lifespan, little is known about how the episodic memory system develops to support the extraction of associative structure from the environment. Here, we relate individual differences in volumes along the hippocampal long axis to performance on statistical learning and associative inference tasks-both of which require encoding associations that span multiple episodes-in a developmental sample ranging from ages 6 to 30 years. Relating age to volume, we found dissociable patterns across the hippocampal long axis, with opposite nonlinear volume changes in the head and body. These structural differences were paralleled by performance gains across the age range on both tasks, suggesting improvements in the cross-episode binding ability from childhood to adulthood. Controlling for age, we also found that smaller hippocampal heads were associated with superior behavioral performance on both tasks, consistent with this region's hypothesized role in forming generalized codes spanning events. Collectively, these results highlight the importance of examining hippocampal development as a function of position along the hippocampal axis and suggest that the hippocampal head is particularly important in encoding associative structure across development.

  11. Experimental study on irradiation injury of the kidneys, 2

    International Nuclear Information System (INIS)

    Tomita, Shinichi; Fuzikawa, Kiyozumi; Nishimori, Issei; Tsuda, Nobuo; Miyagawa, Naotaka

    1976-01-01

    In order to investigate irradiation injury of the kidney and effect of injured kidney on the whole body, especially cardiovascular changes, a single kidney was extracted from Wistar female rats and only the remained kidney was irradiated with a great amount of radiation in 4000 R dose experimentally. After seven weeks of irradiation, atrophy and involution of the highest region of the kidney were found. Histologically, fibrous proliferation of interstice accompanied with atrophy of the renal tubule, and slightly increased nuclei and lobulation of the glomerulus were recognized. After 15 weeks of irradiation, atrophy and involution of the whole kidney were found. Histologically, fibrous proliferation of interstice in the kidney accompanied with high degree atrophy of the renal tubule, marked increase and lobulation of mesangium ground substance of the glomerulus and mild hypertrophy of arteriole were recognized. Mild degeneration of myocardium was recognized. In the long-term cases passing 29 and 34 weeks after irradiation, blood pressure just before slaughter rose to 250 mmHg. The kidney showed malignant nephrosclerosis-like lesion, and panarteritis was found in the mesentery and peri-pancreatic artery. In the heart, hypertonic myocardosis was recognized. A rise of blood pressure which was observed in this experiment occurred in circulation degenerations resulted from the secondary hypertrophy of the blood vessels accompanied with fibrous proliferation of the interstice which appeared after degeneration of renal tubule. It was thought that panarteritis of cardiovascular system of the whole body, especially mesentery and peri-pancreatic artery, and fibrinoid degeneration of arteriole of the kidney were due to hypertension and angiopathic factors (non-vasopressor extracts from the injured kidney). (Tsunoda, M.)

  12. Structural MRI in frontotemporal dementia: comparisons between hippocampal volumetry, tensor-based morphometry and voxel-based morphometry.

    Science.gov (United States)

    Muñoz-Ruiz, Miguel Ángel; Hartikainen, Päivi; Koikkalainen, Juha; Wolz, Robin; Julkunen, Valtteri; Niskanen, Eini; Herukka, Sanna-Kaisa; Kivipelto, Miia; Vanninen, Ritva; Rueckert, Daniel; Liu, Yawu; Lötjönen, Jyrki; Soininen, Hilkka

    2012-01-01

    MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD). However there is a need to develop more accurate and standardized MRI analysis methods. To compare FTD with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) with three automatic MRI analysis methods - Hippocampal Volumetry (HV), Tensor-based Morphometry (TBM) and Voxel-based Morphometry (VBM), in specific regions of interest in order to determine the highest classification accuracy. Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI) and 48 patients with stable MCI (SMCI) were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR), sensitivity (SS) and specificity (SP) between the study groups. We found unequivocal results differentiating controls from FTD with HV (hippocampus left side) (CCR = 0.83; SS = 0.84; SP = 0.80), with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94), and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn) (CCR = 0.87/SS = 0.81/SP = 0.96). VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76), particularly in lateral ventricle (frontal horn, central part and occipital horn) (CCR = 0.73), whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73). TBM resulted in low accuracy (CCR = 0.62) in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55). Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD.

  13. Structural MRI in frontotemporal dementia: comparisons between hippocampal volumetry, tensor-based morphometry and voxel-based morphometry.

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Muñoz-Ruiz

    Full Text Available BACKGROUND: MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD. However there is a need to develop more accurate and standardized MRI analysis methods. OBJECTIVE: To compare FTD with Alzheimer's Disease (AD and Mild Cognitive Impairment (MCI with three automatic MRI analysis methods - Hippocampal Volumetry (HV, Tensor-based Morphometry (TBM and Voxel-based Morphometry (VBM, in specific regions of interest in order to determine the highest classification accuracy. METHODS: Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI and 48 patients with stable MCI (SMCI were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR, sensitivity (SS and specificity (SP between the study groups. RESULTS: We found unequivocal results differentiating controls from FTD with HV (hippocampus left side (CCR = 0.83; SS = 0.84; SP = 0.80, with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94, and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn (CCR = 0.87/SS = 0.81/SP = 0.96. VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76, particularly in lateral ventricle (frontal horn, central part and occipital horn (CCR = 0.73, whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73. TBM resulted in low accuracy (CCR = 0.62 in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55. CONCLUSION: Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD.

  14. Novel Roles for the Insulin-Regulated Glucose Transporter-4 in Hippocampally Dependent Memory.

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    Pearson-Leary, Jiah; McNay, Ewan C

    2016-11-23

    The insulin-regulated glucose transporter-4 (GluT4) is critical for insulin- and contractile-mediated glucose uptake in skeletal muscle. GluT4 is also expressed in some hippocampal neurons, but its functional role in the brain is unclear. Several established molecular modulators of memory processing regulate hippocampal GluT4 trafficking and hippocampal memory formation is limited by both glucose metabolism and insulin signaling. Therefore, we hypothesized that hippocampal GluT4 might be involved in memory processes. Here, we show that, in male rats, hippocampal GluT4 translocates to the plasma membrane after memory training and that acute, selective intrahippocampal inhibition of GluT4-mediated glucose transport impaired memory acquisition, but not memory retrieval. Other studies have shown that prolonged systemic GluT4 blockade causes insulin resistance. Unexpectedly, we found that prolonged hippocampal blockade of glucose transport through GluT4-upregulated markers of hippocampal insulin signaling prevented task-associated depletion of hippocampal glucose and enhanced both working and short-term memory while also impairing long-term memory. These effects were accompanied by increased expression of hippocampal AMPA GluR1 subunits and the neuronal GluT3, but decreased expression of hippocampal brain-derived neurotrophic factor, consistent with impaired ability to form long-term memories. Our findings are the first to show the cognitive impact of brain GluT4 modulation. They identify GluT4 as a key regulator of hippocampal memory processing and also suggest differential regulation of GluT4 in the hippocampus from that in peripheral tissues. The role of insulin-regulated glucose transporter-4 (GluT4) in the brain is unclear. In the current study, we demonstrate that GluT4 is a critical component of hippocampal memory processes. Memory training increased hippocampal GluT4 translocation and memory acquisition was impaired by GluT4 blockade. Unexpectedly, whereas long

  15. Thymus Atrophy and Double-Positive Escape Are Common Features in Infectious Diseases

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    Juliana de Meis

    2012-01-01

    Full Text Available The thymus is a primary lymphoid organ in which bone marrow-derived T-cell precursors undergo differentiation, leading to migration of positively selected thymocytes to the T-cell-dependent areas of secondary lymphoid organs. This organ can undergo atrophy, caused by several endogenous and exogenous factors such as ageing, hormone fluctuations, and infectious agents. This paper will focus on emerging data on the thymic atrophy caused by infectious agents. We present data on the dynamics of thymus lymphocytes during acute Trypanosoma cruzi infection, showing that the resulting thymus atrophy comprises the abnormal release of thymic-derived T cells and may have an impact on host immune response.

  16. Measurement of brain atrophy of aging using x-ray computed tomography

    International Nuclear Information System (INIS)

    Takeda, Shumpei; Matsuzawa, Taiju

    1984-01-01

    We measured brain volume of 1,045 subjects with no brain damage using x-ray computed tomography and investigated brain atrophy of aging. Severity of brain atrophy was estimated by brain atrophy index (BAI): BAI (%)=100 (%)x(cerebrospinal fluid space volume/cranial cavity volume). Atrophy of the brain began with statistical significance in the forties in both sexes. In males 40-49 years of age the mean BAI was 1.0% greater (p<0.001) and the S.D. of BAI was 1.1% greater (p<0.001) than those in their thirties. In females of 40-49 years the mean BAI was 0.5% greater (p<0.001) than that in their thirties, but there was no statistical significance between the two S.D.'s of both decades. The BAI increased exponentially with the increasing age from thirties in both sexes. Correlation coefficients were 0.702 (p< 0.001, n=471) in males and 0.721 (p<0.001, n=480) in females. From the regression coefficients it was calculated that the BAI was doubled in 19.4 years in males and 17.4 years in females after thirties. (author)

  17. Hippocampal MRI volumetry at 3 Tesla: reliability and practical guidance.

    Science.gov (United States)

    Jeukens, Cécile R L P N; Vlooswijk, Mariëlle C G; Majoie, H J Marian; de Krom, Marc C T F M; Aldenkamp, Albert P; Hofman, Paul A M; Jansen, Jacobus F A; Backes, Walter H

    2009-09-01

    Although volumetry of the hippocampus is considered to be an established technique, protocols reported in literature are not described in great detail. This article provides a complete and detailed protocol for hippocampal volumetry applicable to T1-weighted magnetic resonance (MR) images acquired at 3 Tesla, which has become the standard for structural brain research. The protocol encompasses T1-weighted image acquisition at 3 Tesla, anatomic guidelines for manual hippocampus delineation, requirements of delineation software, reliability measures, and criteria to assess and ensure sufficient reliability. Moreover, the validity of the correction for total intracranial volume size was critically assessed. The protocol was applied by 2 readers to the MR images of 36 patients with cryptogenic localization-related epilepsy, 4 patients with unilateral hippocampal sclerosis, and 20 healthy control subjects. The uncorrected hippocampal volumes were 2923 +/- 500 mm3 (mean +/- SD) (left) and 3120 +/- 416 mm3 (right) for the patient group and 3185 +/- 411 mm3 (left) and 3302 +/- 411 mm3 (right) for the healthy control group. The volume of the 4 pathologic hippocampi of the patients with unilateral hippocampal sclerosis was 2980 +/- 422 mm3. The inter-reader reliability values were determined: intraclass-correlation-coefficient (ICC) = 0.87 (left) and 0.86 (right), percentage volume difference (VD) = 7.0 +/- 4.7% (left) and 6.0 +/- 3.8% (right), and overlap ratio (OR) = 0.82 +/- 0.04 (left) and 0.82 +/- 0.03 (right). The positive Pearson correlation between hippocampal volume and total intracranial volume was found to be low: r = 0.48 (P = 0.03, left) and r = 0.62 (P = 0.004, right) and did not significantly reduce the volumetric variances, showing the limited benefit of the brain size correction. A protocol was described to determine hippocampal volumes based on 3 Tesla MR images with high inter-reader reliability. Although the reliability of hippocampal volumetry at 3 Tesla

  18. Differentiation of normal pressure hydrocephalus and cerebral atrophy by computed tomography and spinal infusion test

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    Tans, J T.J. [Nijverheidsorganisatie TNO, The Hague (Netherlands). Dept. of Neurology and Research Unit TNO for Clinical Neurophysiology

    1979-01-01

    The diagnostic value of computed tomography (CT) and spinal infusion test (SIT) was investigated in 27 patients with normal pressure hydrocephalus (NPH) and 35 patients with cerebral atrophy. The most consistent CT finding of NPH was dilatation of the temporal horns, that of cerebral atrophy widening of the convexity sulci. However, 43% of patients with cerebral atrophy demonstrated no cortical atrophy. The SIT showed an excellent relation with isotope cisternography and continuous intracranial pressure recording. NPH and cerebral atrophy were correctly differentiated in 71% by CT and SIT. A normal SIT and a CT scan without the typical features of NPH exclude impairment of cerebrospinal fluid absorption. An abnormal SIT and a CT scan showing ventricular enlargement without dilatation of convexity sulci, require isotope cisternography and possibly intracranial pressure recording to determine the degree of the absorption deficit.

  19. Updating the lamellar hypothesis of hippocampal organization

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    Robert S Sloviter

    2012-12-01

    Full Text Available In 1971, Andersen and colleagues proposed that excitatory activity in the entorhinal cortex propagates topographically to the dentate gyrus, and on through a trisynaptic circuit lying within transverse hippocampal slices or lamellae [Andersen, Bliss, and Skrede. 1971. Lamellar organization of hippocampal pathways. Exp Brain Res 13, 222-238]. In this way, a relatively simple structure might mediate complex functions in a manner analogous to the way independent piano keys can produce a nearly infinite variety of unique outputs. The lamellar hypothesis derives primary support from the lamellar distribution of dentate granule cell axons (the mossy fibers, which innervate dentate hilar neurons and area CA3 pyramidal cells and interneurons within the confines of a thin transverse hippocampal segment. Following the initial formulation of the lamellar hypothesis, anatomical studies revealed that unlike granule cells, hilar mossy cells, CA3 pyramidal cells, and Layer II entorhinal cells all form axonal projections that are more divergent along the longitudinal axis than the clearly lamellar mossy fiber pathway. The existence of pathways with translamellar distribution patterns has been interpreted, incorrectly in our view, as justifying outright rejection of the lamellar hypothesis [Amaral and Witter. 1989. The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31, 571-591]. We suggest that the functional implications of longitudinally-projecting axons depend not on whether they exist, but on what they do. The observation that focal granule cell layer discharges normally inhibit, rather than excite, distant granule cells suggests that longitudinal axons in the dentate gyrus may mediate "lateral" inhibition and define lamellar function, rather than undermine it. In this review, we attempt a reconsideration of the evidence that most directly impacts the physiological concept of hippocampal lamellar

  20. Muscle morphometric effect of anterior cruciate ligament injury measured by computed tomography: aspects on using non-injured leg as control

    Science.gov (United States)

    2013-01-01

    Background Anterior cruciate ligament (ACL) tears are common, functionally disabling, and predispose to subsequent injuries and early onset of osteoarthritis in the knee. Injuries result in muscular atrophy and impaired muscular activation. To optimize surgical methods and rehabilitation strategies, knowledge of the effects of ACL injuries on muscles size and function is needed. Asymmetry due to limb dominance implies that the effect of ACL-injury might be different in right-sided and left-sided injuries which, should be taken in account when evaluating the effect of an injury. Evaluation of the effects of injuries is usually made with the contralateral leg as control. The aim of this study is to describe the effect of ACL-injuries on thigh muscle size and also to analyze feasibility of using contralateral limb as control. Methods Sixty-two patients scheduled to undergo ACL reconstruction were examined with computed tomography (CT). Muscle cross sectional area (CSA) was recorded for quadriceps, hamstrings, gracilis and sartorius 15 cm above the knee joint. Comparisons were made between the injured and non-injured side and between individuals separated by gender and side of injury. Comparisons were also made for patients with or without concomitant meniscal tear, for patients differing in time between injury and examinations and for patients with different level of physical activity after the injury. Results Quadriceps CSA was 5% smaller on the injured side. There was an indication that the muscles of the right thigh were generally bigger than those of the left thigh. The difference between the injured and the non-injured side was larger for right-sided injuries than for left-sided. There was also a greater difference in semimembranosus for women than for men. There were no differences related to meniscal injury, time since injury or physical activity. Conclusion The use of contralateral leg for evaluating the effect of ACL-injury is often the only available

  1. MRI characterization of temporal lobe epilepsy using rapidly measurable spatial indices with hemisphere asymmetries and gender features

    International Nuclear Information System (INIS)

    Datta, Siddhartha; Chakrabarti, Nilkanta; Sarkar, Sudipta; Chakraborty, Sumit; Basu, Swadhapriya; Mulpuru, Sai Krishna; Tiwary, Basant K.; Roy, Prasun Kumar

    2015-01-01

    The paucity of morphometric markers for hemispheric asymmetries and gender variations in hippocampi and amygdalae in temporal lobe epilepsy (TLE) calls for better characterization of TLE by finding more useful prognostic MRI parameter(s). T1-weighted MRI (3 T) morphometry using multiple parameters of hippocampus-parahippocampus (angular and linear measures, volumetry) and amygdalae (volumetry) including their hemispheric asymmetry indices (AI) were evaluated in both genders. The cutoff values of parameters were statistically estimated from measurements of healthy subjects to characterize TLE (57 patients, 55 % male) alterations. TLE had differential categories with hippocampal atrophy, parahippocampal angle (PHA) acuteness, and several other parametric changes. Bilateral TLE categories were much more prevalent compared to unilateral TLE categories. Female patients were considerably more disposed to bilateral TLE categories than male patients. Male patients displayed diverse categories of unilateral abnormalities. Few patients (both genders) had combined bilateral appearances of hippocampal atrophy, amygdala atrophy, PHA acuteness, and increase in hippocampal angle (HA) where medial distance ratio (MDR) varied among genders. TLE had gender-specific and hemispheric dominant alterations in AI of parameters. Maximum magnitude of parametric changes in TLE includes (a) AI increase in HA of both genders, (b) HA increase (bilateral) in female patients, and (c) increase in ratio of amygdale/hippocampal volume (unilateral, right hemispheric), and AI decrease in MDR, in male patients. Multiparametric MRI studies of hippocampus and amygdalae, including their hemispheric asymmetry, underscore better characterization of TLE. Rapidly measurable single-slice parameters (HA, PHA, MDR) can readily delineate TLE in a time-constrained clinical setting, which contrasts with customary three-dimensional hippocampal volumetry that requires many slice computation. (orig.)

  2. MRI characterization of temporal lobe epilepsy using rapidly measurable spatial indices with hemisphere asymmetries and gender features

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Siddhartha; Chakrabarti, Nilkanta [University of Calcutta, Department of Physiology and UGC-CPEPA Centre for ' ' Electro-physiological and Neuro-imaging studies including Mathematical Modelling' ' , Kolkata (India); Sarkar, Sudipta; Chakraborty, Sumit; Basu, Swadhapriya [IPGME and R, SSKM Hospital, Department of Radiodiagnosis, Kolkata (India); Mulpuru, Sai Krishna [National Brain Research Centre, National Neuro-Imaging Facility, Manesar (India); Tiwary, Basant K. [Pondicherry University, Centre for Bioinformatics, School of Life Sciences, Pondicherry (India); Roy, Prasun Kumar [National Brain Research Centre, Computational Neuroimaging Division, Manesar (India); National Brain Research Centre, Clinical Neuroscience Unit, Gurgaon (India)

    2015-09-15

    The paucity of morphometric markers for hemispheric asymmetries and gender variations in hippocampi and amygdalae in temporal lobe epilepsy (TLE) calls for better characterization of TLE by finding more useful prognostic MRI parameter(s). T1-weighted MRI (3 T) morphometry using multiple parameters of hippocampus-parahippocampus (angular and linear measures, volumetry) and amygdalae (volumetry) including their hemispheric asymmetry indices (AI) were evaluated in both genders. The cutoff values of parameters were statistically estimated from measurements of healthy subjects to characterize TLE (57 patients, 55 % male) alterations. TLE had differential categories with hippocampal atrophy, parahippocampal angle (PHA) acuteness, and several other parametric changes. Bilateral TLE categories were much more prevalent compared to unilateral TLE categories. Female patients were considerably more disposed to bilateral TLE categories than male patients. Male patients displayed diverse categories of unilateral abnormalities. Few patients (both genders) had combined bilateral appearances of hippocampal atrophy, amygdala atrophy, PHA acuteness, and increase in hippocampal angle (HA) where medial distance ratio (MDR) varied among genders. TLE had gender-specific and hemispheric dominant alterations in AI of parameters. Maximum magnitude of parametric changes in TLE includes (a) AI increase in HA of both genders, (b) HA increase (bilateral) in female patients, and (c) increase in ratio of amygdale/hippocampal volume (unilateral, right hemispheric), and AI decrease in MDR, in male patients. Multiparametric MRI studies of hippocampus and amygdalae, including their hemispheric asymmetry, underscore better characterization of TLE. Rapidly measurable single-slice parameters (HA, PHA, MDR) can readily delineate TLE in a time-constrained clinical setting, which contrasts with customary three-dimensional hippocampal volumetry that requires many slice computation. (orig.)

  3. Combining the boundary shift integral and tensor-based morphometry for brain atrophy estimation

    Science.gov (United States)

    Michalkiewicz, Mateusz; Pai, Akshay; Leung, Kelvin K.; Sommer, Stefan; Darkner, Sune; Sørensen, Lauge; Sporring, Jon; Nielsen, Mads

    2016-03-01

    Brain atrophy from structural magnetic resonance images (MRIs) is widely used as an imaging surrogate marker for Alzheimers disease. Their utility has been limited due to the large degree of variance and subsequently high sample size estimates. The only consistent and reasonably powerful atrophy estimation methods has been the boundary shift integral (BSI). In this paper, we first propose a tensor-based morphometry (TBM) method to measure voxel-wise atrophy that we combine with BSI. The combined model decreases the sample size estimates significantly when compared to BSI and TBM alone.

  4. Neuroprotective mechanism of Lycium barbarum polysaccharides against hippocampal-dependent spatial memory deficits in a rat model of obstructive sleep apnea.

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    Chun-Sing Lam

    Full Text Available Chronic intermittent hypoxia (CIH is a hallmark of obstructive sleep apnea (OSA, which induces hippocampal injuries mediated by oxidative stress. This study aims to examine the neuroprotective mechanism of Lycium barbarum polysaccharides (LBP against CIH-induced spatial memory deficits. Adult Sprague-Dawley rats were exposed to hypoxic treatment resembling a severe OSA condition for a week. The animals were orally fed with LBP solution (1 mg/kg daily 2 hours prior to hypoxia or in air for the control. The effect of LBP on the spatial memory and levels of oxidative stress, inflammation, endoplasmic reticulum (ER stress, apoptosis and neurogenesis in the hippocampus was examined. There was a significant deficit in the spatial memory and an elevated level of malondialdehyde with a decreased expression of antioxidant enzymes (SOD, GPx-1 in the hypoxic group when compared with the normoxic control. In addition, redox-sensitive nuclear factor kappa B (NFКB canonical pathway was activated with a translocation of NFКB members (p65, p50 and increased expression levels of NFКB-dependent inflammatory cytokines and mediator (TNFα, IL-1β, COX-2; also, a significantly elevated level of ER stress (GRP78/Bip, PERK, CHOP and autophagic flux in the hypoxic group, leading to neuronal apoptosis in hippocampal subfields (DG, CA1, CA3. Remarkably, LBP administration normalized the elevated level of oxidative stress, neuroinflammation, ER stress, autophagic flux and apoptosis induced by hypoxia. Moreover, LBP significantly mitigated both the caspase-dependent intrinsic (Bax, Bcl2, cytochrome C, cleaved caspase-3 and extrinsic (FADD, cleaved caspase-8, Bid signaling apoptotic cascades. Furthermore, LBP administration prevented the spatial memory deficit and enhanced the hippocampal neurogenesis induced by hypoxia. Our results suggest that LBP is neuroprotective against CIH-induced hippocampal-dependent spatial memory deficits by promoting hippocampal neurogenesis

  5. Hyaluronate fragments reverse skin atrophy by a CD44-dependent mechanism.

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    Gürkan Kaya

    2006-12-01

    Full Text Available BACKGROUND: Skin atrophy is a common manifestation of aging and is frequently accompanied by ulceration and delayed wound healing. With an increasingly aging patient population, management of skin atrophy is becoming a major challenge in the clinic, particularly in light of the fact that there are no effective therapeutic options at present. METHODS AND FINDINGS: Atrophic skin displays a decreased hyaluronate (HA content and expression of the major cell-surface hyaluronate receptor, CD44. In an effort to develop a therapeutic strategy for skin atrophy, we addressed the effect of topical administration of defined-size HA fragments (HAF on skin trophicity. Treatment of primary keratinocyte cultures with intermediate-size HAF (HAFi; 50,000-400,000 Da but not with small-size HAF (HAFs; 400,000 Da induced wild-type (wt but not CD44-deficient (CD44-/- keratinocyte proliferation. Topical application of HAFi caused marked epidermal hyperplasia in wt but not in CD44-/- mice, and significant skin thickening in patients with age- or corticosteroid-related skin atrophy. The effect of HAFi on keratinocyte proliferation was abrogated by antibodies against heparin-binding epidermal growth factor (HB-EGF and its receptor, erbB1, which form a complex with a particular isoform of CD44 (CD44v3, and by tissue inhibitor of metalloproteinase-3 (TIMP-3. CONCLUSIONS: Our observations provide a novel CD44-dependent mechanism for HA oligosaccharide-induced keratinocyte proliferation and suggest that topical HAFi application may provide an attractive therapeutic option in human skin atrophy.

  6. Adult hippocampal neurogenesis and cognitive aging

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    Román Darío Moreno Fernández

    2013-12-01

    Full Text Available Aging is a normal developmental process associated with neurobiological changes leading to cognitive alterations with preserved, impaired, and enhanced functions. Evidence from animal and human studies is reviewed to explore the potential role of hippocampal plasticity on age-related cognitive changes with special attention to adult hippocampal neurogenesis. Results from lesion and stimulation strategies, as well as correlation data, support either a direct or modulatory role for adult newborn neurons in cognition at advanced ages. Further research on this topic may help to develop new treatments and to improve the quality of life of older people.

  7. Hydrocolonotherapy ankle joints after injuries

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    Volodymyr Muchin

    2016-02-01

    Full Text Available Purpose: to improve efficiency of gydrokinesitherapy by means of specially designed devices and monolasts for patients after ankle joint injuries. Material & Methods: there are pedagogical methods, clinical and radiological methods, anthropometric measurements and goniometry were used. Results: the author's technique of hydrokinesitherapy with application hydrokinesimechanotherapy device in the program of physical rehabilitation which provides optimum conditions for the recovery process was developed. Conclusions: the specially designed hydrokinesomechanotherapeutic device and monolasts are allow strictly controlled movement in all planes of the ankle joint, which contributes to the acceleration of the recovery; the conducted anthropometric and goniometric studies were indicate more rapid elimination of edema, increase movement amplitude, carries opposition to the development of contractures and muscle atrophy.

  8. Management of Lower Extremity Long-bone Fractures in Spinal Cord Injury Patients.

    Science.gov (United States)

    Schulte, Leah M; Scully, Ryan D; Kappa, Jason E

    2017-09-01

    The AO classification system, used as a guide for modern fracture care and fixation, follows a basic philosophy of care that emphasizes early mobility and return to function. Lower extremity long-bone fractures in patients with spinal cord injury often are pathologic injuries that present unique challenges, to which the AO principles may not be entirely applicable. Optimal treatment achieves healing without affecting the functional level of the patient. These injuries often result from low-energy mechanisms in nonambulatory patients with osteopenic bone and a thin, insensate soft-tissue envelope. The complication rate can be high, and the outcomes can be catastrophic without proper care. Satisfactory results can be obtained through various methods of immobilization. Less frequently, internal fixation is applied. In certain cases, after discussion with the patient, amputation may be suitable. Prevention strategies aim to minimize bone loss and muscle atrophy.

  9. Disease-Induced Skeletal Muscle Atrophy and Fatigue

    NARCIS (Netherlands)

    Powers, Scott K.; Lynch, Gordon S.; Murphy, Kate T.; Reid, Michael B.; Zijdewind, Inge

    2016-01-01

    Numerous health problems including acute critical illness, cancer, diseases associated with chronic inflammation, and neurological disorders often result in skeletal muscle weakness and fatigue. Disease-related muscle atrophy and fatigue is an important clinical problem because acquired skeletal

  10. Prevalence and pattern of gluteus medius and minimus tendon pathology and muscle atrophy in older individuals using MRI

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    Chi, Andrew S. [University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States); Long, Suzanne S.; Zoga, Adam C.; Read, Paul J.; Deely, Diane M.; Parker, Laurence; Morrison, William B. [Thomas Jefferson University Hospital, Department of Radiology, Philadelphia, PA (United States)

    2015-12-15

    To evaluate gluteus medius and minimus tendon pathology and muscle atrophy in older individuals using MRI. A retrospective MRI study of 185 individuals was performed. The inclusion criterion was age ≥50. Exclusion criteria were hip surgery, fracture, infection, tumor, or inadequate image quality. Greater trochanteric bursitis was graded none, mild, moderate, or severe. Gluteus medius, gluteus minimus, and iliopsoas tendinopathy was graded normal, tendinosis, low-grade partial tear, high-grade partial tear, or full thickness tear. Gluteus medius, gluteus minimus, tensor fascia lata, and iliopsoas muscle atrophy was scored using a standard scale. Insertion site of tendinopathy and location of muscle atrophy were assessed. Descriptive and statistical analysis was performed. There was increasing greater trochanteric bursitis and gluteus medius and minimus tendinopathy and atrophy with advancing age with moderate to strong positive associations (p < 0.0001) for age and tendinopathy, age and atrophy, bursitis and tendinopathy, and tendinopathy and atrophy for the gluteus medius and minimus. There is a weak positive association (p < 0.0001) for age and tensor fascia lata atrophy, and no statistically significant association between age and tendinopathy or between age and atrophy for the iliopsoas. Fisher's exact tests were statistically significant (p < 0.0001) for insertion site of tendon pathology and location of muscle atrophy for the gluteus medius. Gluteus medius and minimus tendon pathology and muscle atrophy increase with advancing age with progression of tendinosis to low-grade tendon tears to high-grade tendon tears. There is an associated progression in atrophy of these muscles, which may be important in fall-related hip fractures. (orig.)

  11. Prevalence and pattern of gluteus medius and minimus tendon pathology and muscle atrophy in older individuals using MRI

    International Nuclear Information System (INIS)

    Chi, Andrew S.; Long, Suzanne S.; Zoga, Adam C.; Read, Paul J.; Deely, Diane M.; Parker, Laurence; Morrison, William B.

    2015-01-01

    To evaluate gluteus medius and minimus tendon pathology and muscle atrophy in older individuals using MRI. A retrospective MRI study of 185 individuals was performed. The inclusion criterion was age ≥50. Exclusion criteria were hip surgery, fracture, infection, tumor, or inadequate image quality. Greater trochanteric bursitis was graded none, mild, moderate, or severe. Gluteus medius, gluteus minimus, and iliopsoas tendinopathy was graded normal, tendinosis, low-grade partial tear, high-grade partial tear, or full thickness tear. Gluteus medius, gluteus minimus, tensor fascia lata, and iliopsoas muscle atrophy was scored using a standard scale. Insertion site of tendinopathy and location of muscle atrophy were assessed. Descriptive and statistical analysis was performed. There was increasing greater trochanteric bursitis and gluteus medius and minimus tendinopathy and atrophy with advancing age with moderate to strong positive associations (p < 0.0001) for age and tendinopathy, age and atrophy, bursitis and tendinopathy, and tendinopathy and atrophy for the gluteus medius and minimus. There is a weak positive association (p < 0.0001) for age and tensor fascia lata atrophy, and no statistically significant association between age and tendinopathy or between age and atrophy for the iliopsoas. Fisher's exact tests were statistically significant (p < 0.0001) for insertion site of tendon pathology and location of muscle atrophy for the gluteus medius. Gluteus medius and minimus tendon pathology and muscle atrophy increase with advancing age with progression of tendinosis to low-grade tendon tears to high-grade tendon tears. There is an associated progression in atrophy of these muscles, which may be important in fall-related hip fractures. (orig.)

  12. Interleukin-17A Promotes Parietal Cell Atrophy by Inducing ApoptosisSummary

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    Kevin A. Bockerstett

    Full Text Available Background & Aims: Atrophic gastritis caused by chronic inflammation in the gastric mucosa leads to the loss of gastric glandular cells, including acid-secreting parietal cells. Parietal cell atrophy in a setting of chronic inflammation induces spasmolytic polypeptide expressing metaplasia, a critical step in gastric carcinogenesis. However, the mechanisms by which inflammation causes parietal cell atrophy and spasmolytic polypeptide expressing metaplasia are not well defined. We investigated the role of interleukin-17A (IL-17A in causing parietal cell atrophy. Methods: A mouse model of autoimmune atrophic gastritis was used to examine IL-17A production during early and late stages of disease. Organoids derived from corpus glands were used to determine the direct effects of IL-17A on gastric epithelial cells. Immunofluorescent staining was used to examine IL-17A receptors and the direct effect of signaling on parietal cells. Mice were infected with an IL-17A-producing adenovirus to determine the effects of IL-17A on parietal cells in vivo. Finally, IL-17A neutralizing antibodies were administered to mice with active atrophic gastritis to evaluate the effects on parietal cell atrophy and metaplasia. Results: Increased IL-17A correlated with disease severity in mice with chronic atrophic gastritis. IL-17A caused caspase-dependent gastric organoid degeneration, which could not be rescued with a necroptosis inhibitor. Parietal cells expressed IL-17A receptors and IL-17A treatment induced apoptosis in parietal cells. Overexpressing IL-17A in vivo induced caspase-3 activation and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling staining in parietal cells. Finally, IL-17A neutralizing antibody decreased parietal cell atrophy and metaplasia in mice with chronic atrophic gastritis. Conclusions: These data identify IL-17A as a cytokine that promotes parietal cell apoptosis during atrophic gastritis, a

  13. Radiological and clinical evaluation of the delayed outcomes of the cranio-cerebral injuries

    International Nuclear Information System (INIS)

    Boguslawska-Staniaszczyk

    1995-01-01

    The CT images in 100 patients with recent cranio-cerebral injuries were compared to their clinical pictures, including EEG, neurological and psychological examinations, after one year. Mixed changes in the initial CT predicted to more frequent brain tissue scars, posthemorrhagic cavities, cortex atrophy and ventricle system dilatation. EEG appeared more useful method than CT for detection if brain focal lesion only in the patients with posttraumatic epilepsy. (author)

  14. Adult hippocampal neurogenesis in natural populations of mammals.

    Science.gov (United States)

    Amrein, Irmgard

    2015-05-01

    This review will discuss adult hippocampal neurogenesis in wild mammals of different taxa and outline similarities with and differences from laboratory animals. It begins with a review of evidence for hippocampal neurogenesis in various mammals, and shows the similar patterns of age-dependent decline in cell proliferation in wild and domesticated mammals. In contrast, the pool of immature neurons that originate from proliferative activity varies between species, implying a selective advantage for mammals that can make use of a large number of these functionally special neurons. Furthermore, rapid adaptation of hippocampal neurogenesis to experimental challenges appears to be a characteristic of laboratory rodents. Wild mammals show species-specific, rather stable hippocampal neurogenesis, which appears related to demands that characterize the niche exploited by a species rather than to acute events in the life of its members. Studies that investigate adult neurogenesis in wild mammals are not numerous, but the findings of neurogenesis under natural conditions can provide new insights, and thereby also address the question to which cognitive demands neurogenesis may respond during selection. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  15. Shining a light on posterior cortical atrophy.

    Science.gov (United States)

    Crutch, Sebastian J; Schott, Jonathan M; Rabinovici, Gil D; Boeve, Bradley F; Cappa, Stefano F; Dickerson, Bradford C; Dubois, Bruno; Graff-Radford, Neill R; Krolak-Salmon, Pierre; Lehmann, Manja; Mendez, Mario F; Pijnenburg, Yolande; Ryan, Natalie S; Scheltens, Philip; Shakespeare, Tim; Tang-Wai, David F; van der Flier, Wiesje M; Bain, Lisa; Carrillo, Maria C; Fox, Nick C

    2013-07-01

    Posterior cortical atrophy (PCA) is a clinicoradiologic syndrome characterized by progressive decline in visual processing skills, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Misdiagnosis of PCA is common, owing not only to its relative rarity and unusual and variable presentation, but also because patients frequently first seek the opinion of an ophthalmologist, who may note normal eye examinations by their usual tests but may not appreciate cortical brain dysfunction. Seeking to raise awareness of the disease, stimulate research, and promote collaboration, a multidisciplinary group of PCA research clinicians formed an international working party, which had its first face-to-face meeting on July 13, 2012 in Vancouver, Canada, prior to the Alzheimer's Association International Conference. Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  16. Isolated and painless (? atrophy of the infraspinatus muscle: left handed versus right handed volleyball players

    Directory of Open Access Journals (Sweden)

    Thiago D. Gonçalves Côelho

    1994-12-01

    Full Text Available The suprascapular nerve originates from the upper trunk of the brachial plexus or less frequently from the root of C5. It runs a short way and crosses the suprascapular notch. It innervates the supraspinatus muscle and the acromioclavicular and glenohumeral joints. Then, it crosses the lateral edge of the spine of the scapula passing through the spinoglenoid notch, and innervates the infraspinatus muscle. These are potential sites of injury to the suprascapular nerve. Three cases of suprascapular nerve entrapment causing an isolated infraspinatus muscle atrophy in volleyball players were studied. It is suggested the hypothesis that the nature of the smash, in which the athlete uses the arm violently, more than does in volleyball service or in the art of reception, is the key to the pathogenesis of the lesion in volleyball players.

  17. Stress-Induced Neurodegeneration: Mechanisms and Interventions

    National Research Council Canada - National Science Library

    Meyerhoff, James

    2000-01-01

    .... chronic stress in several species, including mouse, rat, tree shrew and monkey, have been reported to develop alterations in hippocampal morphology, including apical dendritic atrophy, depletion...

  18. Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report

    Directory of Open Access Journals (Sweden)

    Scola Rosana Herminia

    2001-01-01

    Full Text Available We report the case of a 3-1/2-year-old girl with hypotonia, multiple joint contractures, hip luxation, arachnodactyly, adducted thumbs, dolichostenomelia, and abnormal external ears suggesting the diagnosis of congenital contractural arachnodactyly (CCA. The serum muscle enzimes were normal and the needle electromyography showed active and chronic denervation. The muscle biopsy demonstrated active and chronic denervation compatible with spinal muscular atrophy. Analysis of exons 7 and 8 of survival motor neuron gene through polymerase chain reaction did not show deletions. Neurogenic muscular atrophy is a new abnormality associated with CCA, suggesting that CCA is clinically heterogeneous.

  19. Atrophy of sacrospinal muscle groups in patients with chronic, diffusely radiating lumbar back pain

    Energy Technology Data Exchange (ETDEWEB)

    Laasonen, E.M.

    1984-01-01

    After surgery necessitated by lumbar back pain syndromes, radiolucency verified by CT may appear in the sacrospinal muscle group on the operate side. This radiolucency represents muscular atrophy and is in its most severe form a result of the replacement of muscle tissue with adipose tissue. Such muscular atrophy appeared in the present series in 31 out of all 156 patients (19.9%) and in 29 out of 94 patients operated on because of radiating lumbar back pain (30.9%). The radiological appearance, extent, and HU values of this muscular atrophy are presented in detail. Only weak correlations with the multitude of clinical symptoms and signs were found in this retrospective study. The effects of irreversible muscular atrophy on the indications for surgery and physiotherapy are discussed.

  20. Remote semantic memory is impoverished in hippocampal amnesia.

    Science.gov (United States)

    Klooster, Nathaniel B; Duff, Melissa C

    2015-12-01

    The necessity of the hippocampus for acquiring new semantic concepts is a topic of considerable debate. However, it is generally accepted that any role the hippocampus plays in semantic memory is time limited and that previously acquired information becomes independent of the hippocampus over time. This view, along with intact naming and word-definition matching performance in amnesia, has led to the notion that remote semantic memory is intact in patients with hippocampal amnesia. Motivated by perspectives of word learning as a protracted process where additional features and senses of a word are added over time, and by recent discoveries about the time course of hippocampal contributions to on-line relational processing, reconsolidation, and the flexible integration of information, we revisit the notion that remote semantic memory is intact in amnesia. Using measures of semantic richness and vocabulary depth from psycholinguistics and first and second language-learning studies, we examined how much information is associated with previously acquired, highly familiar words in a group of patients with bilateral hippocampal damage and amnesia. Relative to healthy demographically matched comparison participants and a group of brain-damaged comparison participants, the patients with hippocampal amnesia performed significantly worse on both productive and receptive measures of vocabulary depth and semantic richness. These findings suggest that remote semantic memory is impoverished in patients with hippocampal amnesia and that the hippocampus may play a role in the maintenance and updating of semantic memory beyond its initial acquisition. Copyright © 2015 Elsevier Ltd. All rights reserved.