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Sample records for brain stem atrophy

  1. Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease

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    Kanoto, Masafumi, E-mail: mkanoto@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Hosoya, Takaaki, E-mail: thosoya@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Toyoguchi, Yuuki, E-mail: c-elegans_0201g@mail.goo.ne.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Oda, Atsuko, E-mail: a.oda@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan)

    2013-01-15

    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.

  2. Quantitative Evaluation of Brain Stem Atrophy Using Magnetic Resonance Imaging in Adult Patients with Alexander Disease.

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    Yoshida, Tomokatsu; Yasuda, Rei; Mizuta, Ikuko; Nakagawa, Masanori; Mizuno, Toshiki

    2017-01-01

    Brain MRI in adult patients with Alexander disease (AxD) mainly shows atrophy in the medulla oblongata. However, currently there is no quantitative standard for assessing this atrophy. In this study, we quantitatively evaluated the brain stem of AxD patients with glial fibrillary acidic protein (GFAP) mutation using conventional MRI to evaluate its usefulness as an aid to diagnosing AxD in daily clinical practice. Nineteen AxD patients with GFAP mutation were compared with 14 patients negative for GFAP mutation in whom AxD was suspected due to "atrophy of the medulla oblongata." In the GFAP mutation-positive group, the sagittal diameter of the medulla oblongata, the ratio of the diameter of the medulla oblongata to that of the midbrain (MO/MB), and the ratio of the sagittal diameter of the medulla oblongata to that of the pons (MO/Po) were significantly smaller compared to those of the GFAP mutation-negative group (p < 0.01). The sensitivity and specificity of each parameter were 87.5 and 92.3%, 91.7 and 81.3%, and 88.2 and 100% with a sagittal diameter of the medulla oblongata <9.0 mm, MO/MB <0.60, and sagittal MO/Po <0.46, respectively. These parameters can provide very useful information to differentially diagnose AxD from other disorders associated with brain stem atrophy in adult patients. © 2017 S. Karger AG, Basel.

  3. Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI.

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    Thomas Jubault

    Full Text Available Idiopathic Parkinson's disease (PD is a neurodegenerative disorder characterized by the dysfunction of dopaminergic dependent cortico-basal ganglia loops and diagnosed on the basis of motor symptoms (tremors and/or rigidity and bradykinesia. Post-mortem studies tend to show that the destruction of dopaminergic neurons in the substantia nigra constitutes an intermediate step in a broader neurodegenerative process rather than a unique feature of Parkinson's disease, as a consistent pattern of progression would exist, originating from the medulla oblongata/pontine tegmentum. To date, neuroimaging techniques have been unable to characterize the pre-symptomatic stages of PD. However, if such a regular neurodegenerative pattern were to exist, consistent damages would be found in the brain stem, even at early stages of the disease. We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3 in the brain stem, between the pons and the medulla oblongata. The present study provides in-vivo evidence that brain stem damage may be the first identifiable stage of PD neuropathology, and that the identification of this consistent damage along with other factors could help with earlier diagnosis in the future. This damage could also explain some non-motor symptoms in PD that often precede diagnosis, such as autonomic dysfunction and sleep disorders.

  4. Cube propagation for focal brain atrophy estimation

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    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...

  5. Subacute brain atrophy after radiation therapy for malignant brain tumor

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    Asai, A.; Matsutani, M.; Kohno, T.; Nakamura, O.; Tanaka, H.; Fujimaki, T.; Funada, N.; Matsuda, T.; Nagata, K.; Takakura, K.

    1989-05-15

    Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.

  6. Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact

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    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.

  7. Childhood Brain Stem Glioma Treatment

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    ... factors for brain stem glioma include: Having certain genetic disorders , such as neurofibromatosis type 1 (NF1). The signs and symptoms of brain stem glioma are not the same in every child. Signs ...

  8. 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)....

  9. Subacute sclerosing panencephalitis: brain stem involvement in a peculiar pattern

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    Senol, U. [Akdeniz University, Antalya (Turkey). Faculty of Medicine; Haspolat, S. [Akdeniz University, Antalya (Turkey). Dept. of Child Neurology; Cevikol, C. [Akdeniz University, Antalya (Turkey). Dept. of Radiodiagnostics; Saatci, I. [Hacettepe University (Turkey). Medical Faculty

    2000-12-01

    The most common pattern in subacute sclerosing panencephalitis, is in the cerebral hemisphere white matter on T2-weighted images with or without atrophy. Brain-stem lesions are rare. We report brain-stem involvement in two children with subacute sclerosing panencephalitis. A peculiar pattern, with involvement of the pons with extension to both middle cerebellar peduncles and substantia nigra but sparing the pontine tegmentum, is suggested. (orig.)

  10. Brain atrophy at onset and physical disability in multiple sclerosis

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    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.

  11. Brain atrophy in clinically early relapsing-remitting multiple sclerosis.

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    Chard, D T; Griffin, C M; Parker, G J M; Kapoor, R; Thompson, A J; Miller, D H

    2002-02-01

    Brain atrophy measured by MRI is a potentially useful tool for monitoring disease progression in multiple sclerosis. The location, extent and mechanisms of brain atrophy in early disease are not well documented. Using quantitative MRI, this study investigated whole brain, grey and white matter atrophy in clinically early relapsing-remitting multiple sclerosis and its relationship to lesion measures. Data came from 27 normal control subjects (14 females and 13 males, mean age 36.1 years) and 26 subjects with clinically definite multiple sclerosis (18 females and eight males, mean age 35.1 years, mean delay from first symptom to scan 1.8 years, median Expanded Disability Status Scale score 1.0). All had three-dimensional fast spoiled gradient recall (3D FSPGR), T(1)-weighted pre- and post-gadolinium-enhanced and T(2)-weighted scans. The 3D FSPGR images were automatically segmented into grey and white matter and cerebrospinal fluid using SPM99. 3D FSPGR hypo-intense, T(2) hyper-intense, T(1) hypo-intense and T(1) post-gadolinium-enhancing lesion volumes were determined by semi-automatic lesion segmentation. The SPM99 output was combined with the 3D FSPGR lesion segmentations to quantify tissue volumes as fractions of total intracranial volumes, producing values for the brain parenchymal fraction (BPF), white matter fraction (WMF) and grey matter fraction (GMF). Comparing multiple sclerosis with control subjects, BPF, GMF and WMF were significantly reduced (P lesion volumes were inversely related to BPF (T(2) r = -0.78, P lesion volumes were not correlated with any fractional volumes. These results indicate that significant brain atrophy, affecting both grey and white matter, occurs early in the clinical course of multiple sclerosis. The lack of correlation between lesion load measures and WMF suggests that pathological changes in white matter may occur by mechanisms which are at least partly independent from overt lesion genesis in early multiple sclerosis.

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

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    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.

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

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

    1985-11-01

    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.

  14. Embryonic stem cells improve skeletal muscle recovery after extreme atrophy in mice.

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    Artioli, Guilherme Giannini; De Oliveira Silvestre, João Guilherme; Guilherme, João Paulo Limongi França; Baptista, Igor Luchini; Ramos, Gracielle Vieira; Da Silva, Willian José; Miyabara, Elen Haruka; Moriscot, Anselmo Sigari

    2015-03-01

    We injected embryonic stem cells into mouse tibialis anterior muscles subjected to botulinum toxin injections as a model for reversible neurogenic atrophy. Muscles were exposed to botulinum toxin for 4 weeks and allowed to recover for up to 6 weeks. At the onset of recovery, a single muscle injection of embryonic stem cells was administered. The myofiber cross-sectional area, single twitch force, peak tetanic force, time-to-peak force, and half-relaxation time were determined. Although the stem cell injection did not affect the myofiber cross-sectional area gain in recovering muscles, most functional parameters improved significantly compared with those of recovering muscles that did not receive the stem cell injection. Muscle function recovery was accelerated by embryonic stem cell delivery in this durable neurogenic atrophy model. We conclude that stem cells should be considered a potential therapeutic tool for recovery after extreme skeletal muscle atrophy. © 2014 Wiley Periodicals, Inc.

  15. Intellectual enrichment lessens the effect of brain atrophy on learning and memory in multiple sclerosis.

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    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.

  16. Global brain atrophy and metabolic dysfunction in LGI1 encephalitis

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    Szots, Monika; Blaabjerg, Morten; Orsi, Gergely

    2017-01-01

    Background: Chronic cognitive deficits are frequent in leucin-rich glioma-inactivated 1 protein (LGI1) encephalitis. We examined structural and metabolic brain abnormalities following LGI1 encephalitis and correlated findings with acute and follow-up clinical outcomes. Methods: Nine patients...... underwent prospective multimodal 3 Tesla MRI 33.1 ± 18 months after disease onset, including automated volumetry, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). Data were compared to 9 age- and sex-matched healthy controls. Results: Although extratemporal lesions were not present......: Poor clinical outcome following LGI1 encephalitis is associated with global brain atrophy and disintegration of white matter tracts. The pathological changes affect not only temporomesial structures but also frontal lobes and the cerebellum....

  17. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy

    NARCIS (Netherlands)

    De Vis, J B|info:eu-repo/dai/nl/39133378X; Zwanenburg, J J|info:eu-repo/dai/nl/290473683; van der Kleij, L A|info:eu-repo/dai/nl/413752291; Spijkerman, J M; Biessels, G J|info:eu-repo/dai/nl/165576367; Hendrikse, J|info:eu-repo/dai/nl/266590268; Petersen, E T

    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

  18. Brain Atrophy of Secondary REM-Sleep Behavior Disorder in Neurodegenerative Disease.

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    Kim, Hee-Jin; Im, Hyung Kyun; Kim, Juhan; Han, Jee-Young; de Leon, Mony; Deshpande, Anup; Moon, Won-Jin

    2016-04-05

    Rapid eye movement sleep behavior disorder (RBD) may present as an early manifestation of an evolving neurodegenerative disorder with alpha-synucleinopathy. We investigated that dementia with RBD might show distinctive cortical atrophic patterns. A total of 31 patients with idiopathic Parkinson's disease (IPD), 23 with clinically probable Alzheimer's disease (AD), and 36 healthy controls participated in this study. Patients with AD and IPD were divided into two groups according to results of polysomnography and rated with a validated Korean version of the RBD screening questionnaire (RBDSQ-K), which covers the clinical features of RBD. Voxel-based morphometry was adapted for detection of regional brain atrophy among groups of subjects. Scores on RBDSQ-K were higher in the IPD group (3.54 ± 2.8) than in any other group (AD, 2.94 ± 2.4; healthy controls, 2.31 ± 1.9). Atrophic changes according to RBDSQ-K scores were characteristically in the posterior part of the brain and brain stem, including the hypothalamus and posterior temporal region including the hippocampus and bilateral occipital lobe. AD patients with RBD showed more specialized atrophic patterns distributed in the posterior and inferior parts of the brain including the bilateral temporal and occipital cortices compared to groups without RBD. The IPD group with RBD showed right temporal cortical atrophic changes. The group of patients with neurodegenerative diseases and RBD showed distinctive brain atrophy patterns, especially in the posterior and inferior cortices. These results suggest that patients diagnosed with clinically probable AD or IPD might have mixed pathologies including α-synucleinopathy.

  19. MRI derived brain atrophy in PSP and MSA-P. Determining sample size to detect treatment effects.

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    Paviour, Dominic C; Price, Shona L; Lees, Andrew J; Fox, Nick C

    2007-04-01

    Progressive supranuclear palsy (PSP) and multiple system (MSA) atrophy are associated with progressive brain atrophy. Serial MRI can be applied in order to measure this change in brain volume and to calculate atrophy rates. We evaluated MRI derived whole brain and regional atrophy rates as potential markers of progression in PSP and the Parkinsonian variant of multiple system atrophy (MSA-P). 17 patients with PSP, 9 with MSA-P and 18 healthy controls underwent two MRI brain scans. MRI scans were registered, and brain and regional atrophy rates (midbrain, pons, cerebellum, third and lateral ventricles) measured. Sample sizes required to detect the effect of a proposed disease-modifying treatment were estimated. The effect of scan interval on the variance of the atrophy rates and sample size was assessed. Based on the calculated yearly rates of atrophy, for a drug effect equivalent to a 30% reduction in atrophy, fewer PSP subjects are required in each treatment arm when using midbrain rather than whole brain atrophy rates (183 cf. 499). Fewer MSA-P subjects are required, using pontine/cerebellar, rather than whole brain atrophy rates (164/129 cf. 794). A reduction in the variance of measured atrophy rates was observed with a longer scan interval. Regional rather than whole brain atrophy rates calculated from volumetric serial MRI brain scans in PSP and MSA-P provide a more practical and powerful means of monitoring disease progression in clinical trials.

  20. Factors Associated with Changes in Brain Atrophy during a Three-Year Observation in Elderly Diabetic Patients: Effect of Renal Impairment on Hippocampal Atrophy

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    Takahiko Kawamura

    2016-02-01

    Full Text Available Background/Aims: We conducted a 3-year longitudinal study concerning factors associated with changes in brain atrophy in elderly diabetic patients. Methods: We evaluated hippocampal and global brain atrophy using automatic voxel-based morphometry of structural magnetic resonance images, 4 cognitive function tests, and cerebral small vessel disease (SVD in 66 diabetic patients. Results: During the 3-year follow-up, hippocampal and global brain atrophy advanced, and cognitive functions worsened. For changes in hippocampal atrophy, changes in estimated glomerular filtration rate (eGFR, albuminuria, and being an ApoE ε4 carrier were independent factors; change in the number of silent brain infarctions was an independent factor for changes in global brain atrophy. A significant association of changes in eGFR and albuminuria with hippocampal atrophy remained after adjusting for confounders including SVD. Both types of brain atrophy at baseline were significantly correlated with cognitive impairment at baseline and especially associated with changes in delayed word recall during the follow-up after adjusting for confounders. Conclusion: Changes in eGFR and albuminuria during follow-up were independent risk factors for hippocampal atrophy, which was associated with decline in delayed word recall, suggesting that management of chronic kidney disease may prevent the progression of hippocampal atrophy.

  1. Association between blood pressure levels over time and brain atrophy in the elderly

    NARCIS (Netherlands)

    den Heijer, T; Skoog, [No Value; Oudkerk, M; de Leeuw, FE; de Groot, JC; Hofman, A; Breteler, MMB

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  2. Association between blood pressure levels over time and brain atrophy in the elderly.

    NARCIS (Netherlands)

    Heijer, T.; Skoog, I.; Oudkerk, M.; Leeuw, H.F. de; Groot, J.C. de; Hofman, A.W.I.M.; Breteler, M.H.M.

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  3. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder

    NARCIS (Netherlands)

    Wortmann, S.B.; Zietkiewicz, S.; Kousi, M.; Szklarczyk, R.J.; Haack, T.B.; Gersting, S.W.; Muntau, A.C.; Rakovic, A.; Renkema, G.H.; Rodenburg, R.J.; Strom, T.M.; Meitinger, T.; Rubio-Gozalbo, M.E.; Chrusciel, E.; Distelmaier, F.; Golzio, C.; Jansen, J.H.; Karnebeek, C. van; Lillquist, Y.; Lucke, T.; Ounap, K.; Zordania, R.; Yaplito-Lee, J.; Bokhoven, H. van; Spelbrink, J.N.; Vaz, F.M.; Pras-Raves, M.; Ploski, R.; Pronicka, E.; Klein, C.; Willemsen, M.A.A.P.; Brouwer, A.P.M. de; Prokisch, H.; Katsanis, N.; Wevers, R.A.

    2015-01-01

    We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder,

  4. Brain Atrophy and Hypomyelination Associated with Iatrogenic Cushing Syndrome in an Infant.

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    Dogan, Sumeyra; S Dogan, Mehmet; Tutunculer, Filiz; Yapiciugurlar, Ozge; Genchellac, Hakan

    2018-01-01

    Prolonged use of topical corticosteroids, particularly in infants, albeit rare, may lead to Cushing syndrome. Central nervous system abnormalities including brain atrophy and delayed myelination on cranial magnetic resonance imaging has been reported in patients with corticosteroid treatment. We herein report a 5-month-old female infant referred to Department of Pediatric Endocrinology, Edirne, Turkey with brain atrophy and myelination delay that might be due to iatrogenic Cushing syndrome caused by topical corticosteroid use.

  5. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy

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    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.)

  6. Whole-brain atrophy rate and cognitive decline: longitudinal MR study of memory clinic patients

    NARCIS (Netherlands)

    Sluimer, J.D.; van der Flier, W.M.; Karas, G.B.; Fox, N.C.; Scheltens, P.; Barkhof, F.; Vrenken, H.

    2008-01-01

    Purpose: To prospectively determine whole-brain atrophy rate in mild cognitive impairment (MCI) and Alzheimer disease (AD) and its association with cognitive decline, and investigate the risk of progression to dementia in initially non-demented patients given baseline brain volume and whole-brain

  7. Conditioned medium derived from umbilical cord mesenchymal stem cells regenerates atrophied muscles.

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    Kim, Mi Jin; Kim, Z-Hun; Kim, Sun-Mi; Choi, Yong-Soo

    2016-10-01

    We investigated the regenerative effects and regulatory mechanisms of human umbilical cord mesenchymal stem cells (UC-MSCs)-derived conditioned medium (CM) in atrophied muscles using an in vivo model. To determine the appropriate harvest point of UC-CM, active factor content was analyzed in the secretome over time. A muscle atrophy model was induced in rats by hindlimb suspension (HS) for 2 weeks. Next, UC-CM was injected directly into the soleus muscle of both hind legs to assess its regenerative efficacy on atrophy-related factors after 1 week of HS. During HS, muscle mass and muscle fiber size were significantly reduced by over 2-fold relative to untreated controls. Lactate accumulation within the muscles was similarly increased. By contrast, all of the above analytical factors were significantly improved in HS-induced rats by UC-CM injection compared with saline injection. Furthermore, the expression levels of desmin and skeletal muscle actin were significantly elevated by UC-CM treatment. Importantly, UC-CM effectively suppressed expression of the atrophy-related ubiquitin E3-ligases, muscle ring finger 1 and muscle atrophy F-box by 2.3- and 2.1-fold, respectively. UC-CM exerted its actions by stimulating the phosphoinositol-3-kinase (PI3K)/Akt signaling cascade. These findings suggest that UC-CM provides an effective stimulus to recover muscle status and function in atrophied muscles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Alois Alzheimer and vascular brain disease: Arteriosclerotic atrophy of the brain

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    Full Text Available Alois Alzheimer is best known for his description of neurofibrillary changes in brain neurons of a demented patient, identifying a novel disease, soon named after him by Kraepelin. However, the range of his studies was broad, including vascular brain diseases, published between 1894 and 1902. Alzheimer described the clinical picture of Arteriosclerotic atrophy of the brain, differentiating it from other similar disorders. He stated that autopsy allowed pathological distinction between arteriosclerosis and syphilis, thereby achieving some of his objectives of segregating disorders and separating them from syphilis. His studies contributed greatly to establishing the key information on vascular brain diseases, predating the present state of knowledge on the issue, while providing early descriptions of what would be later regarded as the dimensional presentation of the now called "Vascular cognitive impairment", constituted by a spectrum that includes a stage of "Vascular cognitive impairment not dementia" and another of "Vascular dementia".

  9. Brain atrophy rates in Parkinson's disease with and without dementia using serial magnetic resonance imaging.

    Science.gov (United States)

    Burton, Emma J; McKeith, Ian G; Burn, David J; O'Brien, John T

    2005-12-01

    Increased rates of brain atrophy are seen in Alzheimer's disease, but whether rates are similarly increased in other dementias such as Parkinson's disease dementia (PDD) has not been well examined. We determined the rates of brain atrophy using serial magnetic resonance imaging (MRI) in PDD and compared this finding to rates seen in cognitively intact Parkinson's disease (PD) patients and age-matched control subjects. Thirty-one patients (PD = 18, PDD = 13) and 24 age-matched controls underwent serial volumetric 1.5 T MRI scans, approximately 1 year apart. Baseline and repeat scans were registered and quantification of the brain boundary shift integral was used to determine whole-brain atrophy rates. Rates of brain atrophy were significantly increased in PDD (1.12 +/- 0.98%/year) compared to PD (0.31 +/- 0.69%/year; P = 0.018) and control subjects (0.34 +/- 0.76%/year; P = 0.015). There were no differences in atrophy rates between controls and PD (P = 0.79). No correlations between increased atrophy rates and age or dementia severity (Mini-Mental State Examination score) were observed. Serial MRI may be a useful tool for monitoring disease progression in PDD and further studies should investigate its utility for early diagnosis.

  10. The transitional association between β-amyloid pathology and regional brain atrophy.

    Science.gov (United States)

    Insel, Philip S; Mattsson, Niklas; Donohue, Michael C; Mackin, R Scott; Aisen, Paul S; Jack, Clifford R; Shaw, Leslie M; Trojanowski, John Q; Weiner, Michael W

    2015-10-01

    Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid (Aβ) associated with brain atrophy and cognitive decline. The functional form to model the association between Aβ and regional brain atrophy has not been well defined. To determine the relationship between Aβ and atrophy, we compared the performance of the usual dichotomization of cerebrospinal fluid (CSF) Aβ to identify subjects as Aβ+ and Aβ- with a trilinear spline model of CSF Aβ. One hundred and eighty-three subjects with mild cognitive impairment and 108 cognitively normal controls with baseline CSF Aβ and up to 4 years of longitudinal magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative were analyzed using mixed-effects regression. Piecewise-linear splines were used to evaluate the nonlinear nature of the association between CSF Aβ and regional atrophy and to identify points of acceleration of atrophy with respect to Aβ. Several parameterizations of CSF Aβ were compared using likelihood ratio tests and the Akaike information criterion. Periods of acceleration of atrophy in which subjects transition from CSF Aβ negativity to CSF Aβ positivity were estimated from the spline models and tested for significance. Spline models resulted in better fits for many temporal and parietal regions compared with the dichotomous models. The trilinear model showed that periods of acceleration of atrophy varied greatly by region with early changes seen in the insula, amygdala, precuneus, hippocampus, and other temporal regions, occurring before the clinical threshold for CSF Aβ positivity. The use of piecewise-linear splines provides an improved model of the nonlinear association between CSF Aβ and regional atrophy in regions implicated in the progression of AD. The important biological finding of this work is that some brain regions show periods of accelerated volume loss well before the CSF Aβ42 threshold. This implies that signs of brain atrophy

  11. 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...... 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 (VCSF) and the T2 of CSF (T2,CSF) was calculated. The correlation between VCSF/T2,CSF and brain atrophy scores [global cortical atrophy (GCA...... 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). CONCLUSION: A fast, fully automated CSF MRI volumetric sequence is an alternative for qualitative atrophy scales. The T2 of the CSF is related to brain atrophy and could thus...

  12. 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

  13. Atrophy-specific MRI brain template for Alzheimer's disease and mild cognitive impairment

    DEFF Research Database (Denmark)

    Fonov, Vladimir; Coupe, Pierrick; Eskildsen, Simon Fristed

    and MCI makes use of a single disease-specific template challenging. We propose a novel approach to generate a continuous four-dimensional template, where the 4th dimension is a surrogate measure of overall brain atrophy. Methods We used MRI scans obtained from the ADNI database (www......Background Rapid brain loss is characteristic for the patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) [1]. Increase of the lateral ventricular volume is strongly correlated with the progression of the disease. High variability in the degree of atrophy for subjects with AD.......loni.ucla.edu/ADNI). Automated methods to estimate intracranial capacity (ICC) and lateral ventricles volume (LVV) [2] was applied to all available datasets at base line. The ratio between LVV and ICC (RLVV) was used as a surrogate measure of overall brain atrophy with mean(standard deviation) value of 2.46(0.87)%. Subsets from...

  14. Evaluating anorexia-related brain atrophy using MP2RAGE-based morphometry.

    Science.gov (United States)

    Boto, José; Gkinis, Georgios; Roche, Alexis; Kober, Tobias; Maréchal, Bénédicte; Ortiz, Nadia; Lövblad, Karl-Olof; Lazeyras, François; Vargas, Maria Isabel

    2017-12-01

    To evaluate brain atrophy in anorexic patients by automated cerebral segmentation with the magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) MRI sequence. Twenty patients (female; mean age, 27.9 years), presenting consecutively for brain MRI between August 2014-December 2016 with clinical suspicion of anorexia nervosa and BMIanorexia nervosa. • Brain changes in anorexia nervosa can be quantitatively and qualitatively followed-up by MRI.

  15. Cerebrospinal Fluid Markers of Neurodegeneration and Rates of Brain Atrophy in Early Alzheimer Disease.

    Science.gov (United States)

    Tarawneh, Rawan; Head, Denise; Allison, Samantha; Buckles, Virginia; Fagan, Anne M; Ladenson, Jack H; Morris, John C; Holtzman, David M

    2015-06-01

    Measures of neuronal loss are likely good surrogates for clinical and radiological disease progression in Alzheimer disease (AD). Cerebrospinal fluid (CSF) markers of neuronal injury or neurodegeneration may offer usefulness in predicting disease progression and guiding outcome assessments and prognostic decisions in clinical trials of disease-modifying therapies. Visinin-like protein 1 (VILIP-1) has demonstrated potential usefulness as a marker of neuronal injury in AD. To investigate the usefulness of CSF VILIP-1, tau, p-tau181, and Aβ42 levels in predicting rates of whole-brain and regional atrophy in early AD and cognitively normal control subjects over time. Longitudinal observational study of brain atrophy in participants with early AD and cognitively normal controls. Study participants had baseline CSF biomarker measurements and longitudinal magnetic resonance imaging assessments for a mean follow-up period of 2 to 3 years. Mixed linear models assessed the ability of standardized baseline CSF biomarker measures to predict rates of whole-brain and regional atrophy over the follow-up period. The setting was The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine in St Louis. Participants (mean age, 72.6 years) were individuals with a clinical diagnosis of very mild AD (n = 23) and cognitively normal controls (n = 64) who were enrolled in longitudinal studies of healthy aging and dementia. The study dates were 2000 to 2010. Correlations between baseline CSF biomarker measures and rates of whole-brain or regional atrophy in the AD and control cohorts over the follow-up period. Baseline CSF VILIP-1, tau, and p-tau181 levels (but not Aβ42 levels) predicted rates of whole-brain and regional atrophy in AD over the follow-up period. Baseline CSF VILIP-1 levels predicted whole-brain (P = .006), hippocampal (P = .01), and entorhinal (P = .001) atrophy rates at least as well as tau and p-tau181 in early AD

  16. Bilingualism as a contributor to cognitive reserve: evidence from brain atrophy in Alzheimer's disease.

    Science.gov (United States)

    Schweizer, Tom A; Ware, Jenna; Fischer, Corinne E; Craik, Fergus I M; Bialystok, Ellen

    2012-09-01

    Much of the research on delaying the onset of symptoms of Alzheimer's disease (AD) has focused on pharmacotherapy, but environmental factors have also been acknowledged to play a significant role. Bilingualism may be one factor contributing to 'cognitive reserve' (CR) and therefore to a delay in symptom onset. If bilingualism is protective, then the brains of bilinguals should show greater atrophy in relevant areas, since their enhanced CR enables them to function at a higher level than would be predicted from their level of disease. We analyzed a number of linear measurements of brain atrophy from the computed tomography (CT) scans of monolingual and bilingual patients diagnosed with probable AD who were matched on level of cognitive performance and years of education. Bilingual patients with AD exhibited substantially greater amounts of brain atrophy than monolingual patients in areas traditionally used to distinguish AD patients from healthy controls, specifically, the radial width of the temporal horn and the temporal horn ratio. Other measures of brain atrophy were comparable for the two groups. Bilingualism appears to contribute to increased CR, thereby delaying the onset of AD and requiring the presence of greater amounts of neuropathology before the disease is manifest. Copyright © 2011 Elsevier Srl. All rights reserved.

  17. Insulin and insulin-like growth factor prevent brain atrophy and cognitive impairment in diabetic rats

    Directory of Open Access Journals (Sweden)

    Predrag Šerbedzija

    2012-01-01

    Full Text Available There are an estimated 36 million dementia patients worldwide. The anticipated tripling of this number by year 2050 will negatively impact the capacity to deliver quality health care. The epidemic in diabetes is particularly troubling, because diabetes is a substantial risk factor for dementia independently of cerebrovascular disease. There is an urgent need to elucidate the pathogenesis of progressive brain atrophy, the cause of dementia, to allow rational design of new therapeutic interventions. This review summarizes recent tests of the hypothesis that the concomitant loss of insulin and insulin-like growth factors (IGFs is the dominant cause for age-dependent, progressive brain atrophy with degeneration and cognitive decline. These tests are the first to show that insulin and IGFs regulate adult brain mass by maintaining brain protein content. Insulin and IGF levels are reduced in diabetes, and replacement of both ligands can prevent loss of total brain protein, widespread cell degeneration, and demyelination. IGF alone prevents retinal degeneration in diabetic rats. It supports synapses and is required for learning and memory. Replacement doses in diabetic rats can cross the blood-brain barrier to prevent hippocampus-dependent memory impairment. Insulin and IGFs are protective despite unabated hyperglycemia in diabetic rats, severely restricting hyperglycemia and its consequences as dominant pathogenic causes of brain atrophy and impaired cognition. These findings have important implications for late-onset Alzheimer′s disease (LOAD where diabetes is a major risk factor, and concomitant decline in insulin and IGF activity suggest a similar pathogenesis for brain atrophy and dementia.

  18. MRI patterns of atrophy and hypoperfusion associations across brain regions in frontotemporal dementia.

    Science.gov (United States)

    Tosun, Duygu; Rosen, Howard; Miller, Bruce L; Weiner, Michael W; Schuff, Norbert

    2012-02-01

    Magnetic Resonance Imaging (MRI) provides various imaging modes to study the brain. We tested the benefits of a joint analysis of multimodality MRI data in combination with a large-scale analysis that involved simultaneously all image voxels using joint independent components analysis (jICA) and compared the outcome to results using conventional voxel-by-voxel unimodality tests. Specifically, we designed a jICA to decompose multimodality MRI data into independent components that explain joint variations between the image modalities as well as variations across brain regions. We tested the jICA design on structural and perfusion-weighted MRI data from 12 patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and 12 cognitively normal elderly individuals. While unimodality analyses showed widespread brain atrophy and hypoperfusion in the patients, jICA further revealed two significant joint components of variations between atrophy and hypoperfusion across brain regions. The 1st joint component revealed associated brain atrophy and hypoperfusion predominantly in the right brain hemisphere in behavioral variant frontotemporal dementia, and the 2nd joint component revealed greater atrophy relative to hypoperfusion affecting predominantly the left hemisphere in behavioral variant frontotemporal dementia. The patterns are consistent with the clinical symptoms of behavioral variant frontotemporal dementia that relate to asymmetric compromises of the left and right brain hemispheres. The joint components also revealed that that structural alterations can be associated with physiological alterations in spatially separated but potentially connected brain regions. Finally, jICA outperformed voxel-by-voxel unimodal tests significantly in terms of an effect size, separating the behavioral variant frontotemporal dementia patients from the controls. Taken together, the results demonstrate the benefit of multimodality MRI in conjunction with jICA for mapping

  19. Brain tumor stem cell dancing

    Directory of Open Access Journals (Sweden)

    Giuseppina Bozzuto

    2014-09-01

    Full Text Available Background. Issues regarding cancer stem cell (CSC movement are important in neurosphere biology as cell-cell or cell-environment interactions may have significant impacts on CSC differentiation and contribute to the heterogeneity of the neurosphere. Aims. Despite the growing body of literature data on the biology of brain tumor stem cells, floating CSC-derived neurospheres have been scarcely characterized from a morphological and ultrastructural point of view. Results. Here we report a morphological and ultrastructural characterization performed by live imaging and scanning electron microscopy. Glioblastoma multiforme (GBM CSC-derived neurospheres are heterogeneous and are constituted by cells, morphologically different, capable of forming highly dynamic structures. These dynamic structures are regulated by not serendipitous cell-cell interactions, and they synchronously pulsate following a cyclic course made of "fast" and "slow" alternate phases. Autocrine/paracrine non canonical Wnt signalling appears to be correlated with the association status of neurospheres. Conclusions. The results obtained suggest that GBM CSCs can behave both as independents cells and as "social" cells, highly interactive with other members of its species, giving rise to a sort of "multicellular organism".

  20. Brain Atrophy Correlates with Severe Enlarged Perivascular Spaces in Basal Ganglia among Lacunar Stroke Patients.

    Directory of Open Access Journals (Sweden)

    Xiaoyu Zhang

    Full Text Available Enlarged perivascular spaces (EPVS correlate with cognitive impairment and incident dementia. However, etiologies for severe basal ganglia EPVS (BG-EPVS are still unclear. Our aim was to investigate the independent risk factors for severe BG-EPVS in patients with acute lacunar stroke.We prospectively identified patients with lacunar stroke (diameter on DWI ≤ 20mm from Jan 2011 to May 2015. Patients with severe BG-EPVS were identified on T2 weighted MRI. Age (± 1 year and sex matched controls were also recruited in the same population (two controls for one case. Vascular risk factors, clinical data, EPVS in centrum semiovale (rated 0 to 4, white matter hyperintensities (WMH (by Fazekas scale, brain atrophy (rated 0 to 6 were compared between two groups. Logistic regression was performed to determine independent risk factors for severe BG-EPVS.During study period, 89 patients with severe BG-EPVS and 178 matched controls were included. Vascular risk factors did not differ between two groups. Patients with severe BG-EPVS had lower level of HbA1c and diastolic BP at admission, but presented with larger infarct size, more severe WMH (including total WMH, periventricular WMH and deep WMH and brain atrophy. In logistic regression, brain atrophy (OR = 1.40; 95%CI 1.13, 1.73 and deep WMH (OR = 1.88; 95%CI 1.24, 2.83 were independent risk factors for severe BG-EPVS.Brain atrophy and deep WMH are independent risk factors for severe BG-EPVS, supporting the hypothesis that brain atrophy may be associated with the development of EPVS in basal ganglia.

  1. The relationship between inflammatory activity and brain atrophy in natalizumab treated patients

    Energy Technology Data Exchange (ETDEWEB)

    Magraner, M., E-mail: majomagbe@ono.com [Multiple Sclerosis Unit, Neurology Service, Hospital Universitari i Politecnic La Fe, Bulevar Sur s/n, 46026 Valencia (Spain); Coret, F., E-mail: coret_fra@gva.es [Multiple Sclerosis Unit, Neurology Service, Hospital Clinic de Valencia, Avda Blasco Ibanez 17, 46010 Valencia (Spain); Casanova, B., E-mail: Casanova_bon@gva.es [Multiple Sclerosis Unit, Neurology Service, Hospital Universitari i Politecnic La Fe, Bulevar Sur s/n, 46026 Valencia (Spain)

    2012-11-15

    Objective: To assess the evolution of brain atrophy and its relationship with inflammatory activity in RRMS patients treated with natalizumab. Methods: Eighteen RRMS patients were prospectively followed up for 18 months after starting natalizumab therapy. Patients were monitored monthly and assessed for signs of relapses, adverse events or disability increase. MRI scans were performed before starting natalizumab and every six months. Cross-sectional T2 lesion volume (T2LV) and the normalized brain volume (NBV) at baseline and 18 months MRI scans were calculated using the Steronauta{sup Registered-Sign} and SIENAx softwares, respectively. Longitudinal Percentage of Brain Volume Change (PBVC) was estimated with SIENA. Linkage between inflammatory activity and brain atrophy was studied. Results: Natalizumab reduced ARR by 67% and cumulative CEL by 87.5%. T2 lesion volume decreased from 1000 mm{sup 3}, to 960 mm{sup 3} (p = 0.006) and NBV decreased from 1.55 Multiplication-Sign 10{sup 5} mm{sup 3} to 1.42 Multiplication-Sign 10{sup 5} mm{sup 3} (p = 0.025). Global PBVC from baseline to 18 months was -2.5%, predominantly during the first six months (0-6 months PBVC -1.7%; 6-12 months PBVC -0.74%; 12-18 months PBVC -0.50%). The number of relapses before treatment was correlated to the PBVC during the first semester (Pearson's coefficient -0.520, p = 0.003), while the number of basal CEL or baseline T2LV did not correlate with brain atrophy rate. During follow-up, nine patients had clinical or radiological inflammatory activity. Their PBVC was significantly higher in the first semester (-2.3% to -1.1%, p = 0.002). Conclusions: Natalizumab reduced relapse rate and CEL in MRI. Brain atrophy predominated in the first semester and was related to previous inflammatory activity.

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

    Directory of Open Access Journals (Sweden)

    Mehrabian Shima

    2012-09-01

    Full Text Available Abstract Background This article reports a rare case of active neurosyphilis in a man with mild to moderate dementia and marked hippocampal atrophy, mimicking early onset Alzheimer’s disease. Few cases have so far described bilateral hippocampal atrophy mimicking Alzheimer’s disease in neurosyphilis. Case presentation The patient presented here is a 33 year old Bulgarian male, whose clinical features include progressive cognitive decline and behavioral changes over the last 18 months. Neuropsychological examination revealed mild to moderate dementia (Mini Mental State Examination score was 16/30 with impaired memory and attention, and executive dysfunction. Pyramidal, and extrapyramidal signs, as well as dysarthria and impairment in coordination, were documented. Brain magnetic resonance imaging showed cortical atrophy with noticeable bilateral hippocampal atrophy. The diagnosis of active neurosyphilis was based on positive results of the 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. At 6 month follow up, improvements were noted clinically, on neuropsychological examinations, and in cerebrospinal fluid samples. 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 which requires early aggressive antibiotic therapy.

  3. Post-mortem Findings in Huntington's Deep Brain Stimulation: A Moving Target Due to Atrophy

    Directory of Open Access Journals (Sweden)

    Vinata Vedam-Mai

    2016-04-01

    Full Text Available Background: Deep brain stimulation (DBS has been shown to be effective for Parkinson’s disease, essential tremor, and primary dystonia. However, mixed results have been reported in Huntington’s disease (HD. Case Report: A single case of HD DBS was identified from the University of Florida DBS Brain Tissue Network. The clinical presentation, evolution, surgical planning, DBS parameters, clinical outcomes, and brain pathological changes are summarized. Discussion: This case of HD DBS revealed that chorea may improve and be sustained. Minimal histopathological changes were noted around the DBS leads. Severe atrophy due to HD likely changed the DBS lead position relative to the internal capsule.

  4. Recommendations to improve imaging and analysis of brain lesion load and atrophy in longitudinal studies of multiple sclerosis

    NARCIS (Netherlands)

    Vrenken, H.; Jenkinson, M.; Horsfield, M.A.; Battaglini, M.; van Schijndel, R.A.; Rostrup, E.; Geurts, J.J.G.; Fisher, E.; Zijdenbos, A.; Ashburner, J.; Miller, D. H.; Filippi, M.; Fazekas, F.; Rovaris, M.; Rovira, A.; Barkhof, F.; De Stefano, N.

    2013-01-01

    Focal lesions and brain atrophy are the most extensively studied aspects of multiple sclerosis (MS), but the image acquisition and analysis techniques used can be further improved, especially those for studying within-patient changes of lesion load and atrophy longitudinally. Improved accuracy and

  5. Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

    OpenAIRE

    Qiao, Guanqun; Li, Qingquan; Peng, Gang; Ma, Jun; Fan, Hongwei; Li, Yingbin

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain t...

  6. Somatosensory and acoustic brain stem reflex myoclonus.

    OpenAIRE

    Shibasaki, H; Kakigi, R; Oda, K; Masukawa, S

    1988-01-01

    A patient with brain stem reflex myoclonus due to a massive midbrain infarct was studied electrophysiologically. Myoclonic jerks were elicited at variable latencies by tapping anywhere on the body or by acoustic stimuli, and mainly involved flexor muscles of upper extremities. The existence of convergence of somatosensory and acoustic inputs in the brain stem was suggested. This myoclonus seemed to be mediated by a mechanism similar to the spino-bulbo-spinal reflex.

  7. Brain atrophy rates in first degree relatives at risk for Alzheimer's

    Directory of Open Access Journals (Sweden)

    Erika J. Lampert

    2014-01-01

    Full Text Available A positive family history (FH raises the risk for late-onset Alzheimer's disease though, other than the known risk conferred by apolipoprotein ε4 (ApoE4, much of the genetic variance remains unexplained. We examined the effect of family history on longitudinal regional brain atrophy rates in 184 subjects (42% FH+, mean age 79.9 with mild cognitive impairment (MCI enrolled in a national biomarker study. An automated image analysis method was applied to T1-weighted MR images to measure atrophy rates for 20 cortical and subcortical regions. Mixed-effects linear regression models incorporating repeated-measures to control for within-subject variation over multiple time points tested the effect of FH over a follow-up of up to 48 months. Most of the 20 regions showed significant atrophy over time. Adjusting for age and gender, subjects with a positive FH had greater atrophy of the amygdala (p < 0.01, entorhinal cortex (p < 0.01, hippocampus (p < 0.053 and cortical gray matter (p < 0.009. However, when E4 genotype was added as a covariate, none of the FH effects remained significant. Analyses by ApoE genotype showed that the effect of FH on amygdala atrophy rates was numerically greater in ε3 homozygotes than in E4 carriers, but this difference was not significant. FH+ subjects had numerically greater 4-year cognitive decline and conversion rates than FH− subjects but the difference was not statistically significant after adjusting for ApoE and other variables. We conclude that a positive family history of AD may influence cortical and temporal lobe atrophy in subjects with mild cognitive impairment, but it does not have a significant additional effect beyond the known effect of the E4 genotype.

  8. Recommendations to improve imaging and analysis of brain lesion load and atrophy in longitudinal studies of multiple sclerosis

    DEFF Research Database (Denmark)

    Vrenken, H; Jenkinson, M; Horsfield, M A

    2013-01-01

    Focal lesions and brain atrophy are the most extensively studied aspects of multiple sclerosis (MS), but the image acquisition and analysis techniques used can be further improved, especially those for studying within-patient changes of lesion load and atrophy longitudinally. Improved accuracy...... resonance image analysis methods for assessing brain lesion load and atrophy, this paper makes recommendations to improve these measures for longitudinal studies of MS. Briefly, they are (1) images should be acquired using 3D pulse sequences, with near-isotropic spatial resolution and multiple image...... contrasts to allow more comprehensive analyses of lesion load and atrophy, across timepoints. Image artifacts need special attention given their effects on image analysis results. (2) Automated image segmentation methods integrating the assessment of lesion load and atrophy are desirable. (3) A standard...

  9. Stem cells to regenerate the newborn brain

    NARCIS (Netherlands)

    van Velthoven, C.T.J.

    2011-01-01

    Perinatal hypoxia-ischemia (HI) is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. In this thesis we investigate whether mesenchymal stem cells (MSC) regenerate the neonatal brain after HI injury. We show that transplantation of MSC after neonatal brain injury

  10. Alzheimer's disease pattern of brain atrophy predicts cognitive decline in Parkinson's disease

    Science.gov (United States)

    Dietz, Nicole; Duda, John E.; Wolk, David A.; Doshi, Jimit; Xie, Sharon X.; Davatzikos, Christos; Clark, Christopher M.; Siderowf, Andrew

    2012-01-01

    Research suggests overlap in brain regions undergoing neurodegeneration in Parkinson's and Alzheimer's disease. To assess the clinical significance of this, we applied a validated Alzheimer's disease-spatial pattern of brain atrophy to patients with Parkinson's disease with a range of cognitive abilities to determine its association with cognitive performance and decline. At baseline, 84 subjects received structural magnetic resonance imaging brain scans and completed the Dementia Rating Scale-2, and new robust and expanded Dementia Rating Scale-2 norms were applied to cognitively classify participants. Fifty-nine non-demented subjects were assessed annually with the Dementia Rating Scale-2 for two additional years. Magnetic resonance imaging scans were quantified using both a region of interest approach and voxel-based morphometry analysis, and a method for quantifying the presence of an Alzheimer's disease spatial pattern of brain atrophy was applied to each scan. In multivariate models, higher Alzheimer's disease pattern of atrophy score was associated with worse global cognitive performance (β = −0.31, P = 0.007), including in non-demented patients (β = −0.28, P = 0.05). In linear mixed model analyses, higher baseline Alzheimer's disease pattern of atrophy score predicted long-term global cognitive decline in non-demented patients [F(1, 110) = 9.72, P = 0.002], remarkably even in those with normal cognition at baseline [F(1, 80) = 4.71, P = 0.03]. In contrast, in cross-sectional and longitudinal analyses there was no association between region of interest brain volumes and cognitive performance in patients with Parkinson's disease with normal cognition. These findings support involvement of the hippocampus and parietal–temporal cortex with cognitive impairment and long-term decline in Parkinson's disease. In addition, an Alzheimer's disease pattern of brain atrophy may be a preclinical biomarker of cognitive decline

  11. Brain Atrophy Estimated from Structural Magnetic Resonance Imaging as a Marker of Large-Scale Network-Based Neurodegeneration in Aging and Stroke

    OpenAIRE

    Michele Veldsman

    2017-01-01

    Brain atrophy is a normal part of healthy aging, and stroke appears to have neurodegenerative effects, accelerating this atrophy to pathological levels. The distributed pattern of atrophy in healthy aging suggests that large-scale brain networks may be involved. At the same time, the network wide effects of stroke are beginning to be appreciated. There is now widespread use of network methods to understand the brain in terms of coordinated brain activity or white matter connectivity. Examinin...

  12. Clinical study on eating disorders. Brain atrophy revealed by cranial computed tomography scans

    Energy Technology Data Exchange (ETDEWEB)

    Nishiwaki, Shinichi

    1988-06-01

    Cranial computed tomography (CT) scans were reviewed in 34 patients with anorexia nervosa (Group I) and 22 with bulimia (Group II) to elucidate the cause and pathological significance of morphological brain alterations. The findings were compared with those from 47 normal women. The incidence of brain atrophy was significantly higher in Group I (17/34, 50%) and Group II (11/22, 50%) than the control group (3/47, 6%). In Group I, there was a significant increase in the left septum-caudate distance, the maximum width of interhemispheric fissure, the width of the both-side Sylvian fissures adjacent to the skull, and the maximum width of the third ventricle. A significant increase in the maximum width of interhemispheric fissure and the width of the left-side Sylvian fissure adjacent to the skull were noted as well in Group II. Ventricular brain ratios were significantly higher in Groups I and II than the control group (6.76 and 7.29 vs 4.55). Brain atrophy did not correlate with age, body weight, malnutrition, eating behavior, depression, thyroid function, EEG findings, or intelligence scale. In Group I, serum cortisol levels after the administration of dexamethasone were correlated with ventricular brain ratio. (Namekawa, K) 51 refs.

  13. Surgery and Brain Atrophy In Cognitively Normal Elderly Subjects and Subjects Diagnosed with Mild Cognitive Impairment

    Science.gov (United States)

    Kline, Richard P.; Pirraglia, Elizabeth; Cheng, Hao; Santi, Susan De; Li, Yi; Haile, Michael; de Leon, Mony J.; Bekker, Alex

    2012-01-01

    Background Structural MRI is used to longitudinally monitor the progression of Alzheimer's disease from its presymptomatic to symptomatic phases. Using magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we tested the hypothesis that surgery would affect brain parameters associated with progression of dementia. Materials and Methods Brain images from the neuroimaging initiative database were used to study normal volunteer subjects and patients with mild cognitive impairment for the age group 55 to 90 inclusive. We compared changes in regional brain anatomy for three visits that defined two inter-visit intervals for a surgical cohort (n=41) and a propensity matched non-surgical control cohort (n = 123). The first interval for the surgical cohort contained the surgical date. Regional brain volumes were determined with Freesurfer and quantitatively described with J-image software (University of California at San Francisco). Statistical analysis used Repeated Measures ANCOVA (SPSS, v.18.0; Chicago, IL). Results We found that surgical patients, during the first follow-up interval (5–9 months), but not subsequently, had increased rates of atrophy for cortical gray matter and hippocampus, and lateral ventricle enlargement, as compared to non-surgical controls. A composite score of five cognitive tests during this interval showed reduced performance for surgical patients with mild cognitive impairment. Conclusions Elderly subjects after surgery experienced an increased rate of brain atrophy during the initial evaluation interval, a time associated with enhanced risk for postoperative cognitive dysfunction. Although there was no difference in atrophy rate by diagnosis, subjects with mild cognitive impairment suffered greater subsequent cognitive effects. PMID:22293721

  14. Sex differences in morphology of the brain stem and cerebellum with normal ageing

    Energy Technology Data Exchange (ETDEWEB)

    Oguro, H.; Okada, K.; Yamaguchi, S.; Kobayashi, S. [Internal Medicine III, Shimane Medical University, Izumo (Japan)

    1998-12-01

    The cerebral hemispheres become atrophic with age. The sex of the individual may affect this process. There are few studies of the effects of age and sex on the brain stem and cerebellum. We used MRI morphometry to study changes in these structures in 152 normal subjects over 40 years of age. In the linear measurements, men showed significant age-associated atrophy in the tegmentum and pretectum of the midbrain and the base of the pons. In women, only the pretectum of the midbrain showed significant ageing effects after the age of 50 years, and thereafter remained rather constant. Only men had significant age-associated reduction in area of the crebellar vermis area after the age of 70 years. Both men and women showed supratentorial brain atrophy that progressed by decades. There were significant correlations between supratentorial brain atrophy and the diameter of the ventral midbrain, pretectum, and base of the pons in men, and between brain atrophy and the diameter of the fourth ventricle in women. (orig.) With 4 figs., 3 tabs., 16 refs.

  15. Neurofibromatosis type 1: brain stem tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bilaniuk, L.T. [Department of Radiology, The Children`s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA (United States); Molloy, P.T. [Division of Neurology, Children`s Hospital of Philadelphia, PA (United States); Zimmerman, R.A. [Department of Radiology, The Children`s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA (United States); Phillips, P.C. [Division of Neurology, Children`s Hospital of Philadelphia, PA (United States); Vaughan, S.N. [Division of Neurology, Children`s Hospital of Philadelphia, PA (United States); Liu, G.T. [Division of Neuro-Ophthalmology, Children`s Hospital of Philadelphia, PA (United States); Sutton, L.N. [Division of Neurosurgery, Children`s Hospital of Philadelphia, PA (United States); Needle, M. [Division of Oncology, The Children`s Hospital of Philadelphia. PA (United States)

    1997-09-01

    We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. (orig.). With 7 figs., 3 tabs.

  16. Carrier screening for spinal muscular atrophy in Italian population

    Indian Academy of Sciences (India)

    Spinal muscular atrophy (SMA) is an autosomal-recessive neuromuscular disorder characterized by motor neuron degeneration in the anterior horn of the spinal cord and brain stem, resulting in progressive muscle weakness and atrophy. The responsible survival motor neuron gene (SMN1; HGNC: 11117) is localized in ...

  17. Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study.

    Science.gov (United States)

    Coughlin, Jennifer M; Wang, Yuchuan; Munro, Cynthia A; Ma, Shuangchao; Yue, Chen; Chen, Shaojie; Airan, Raag; Kim, Pearl K; Adams, Ashley V; Garcia, Cinthya; Higgs, Cecilia; Sair, Haris I; Sawa, Akira; Smith, Gwenn; Lyketsos, Constantine G; Caffo, Brian; Kassiou, Michael; Guilarte, Tomas R; Pomper, Martin G

    2015-02-01

    There are growing concerns about potential delayed, neuropsychiatric consequences (e.g, cognitive decline, mood or anxiety disorders) of sports-related traumatic brain injury (TBI). Autopsy studies of brains from a limited number of former athletes have described characteristic, pathologic changes of chronic traumatic encephalopathy (CTE) leading to questions about the relationship between these pathologic and the neuropsychiatric disturbances seen in former athletes. Research in this area will depend on in vivo methods that characterize molecular changes in the brain, linking CTE and other sports-related pathologies with delayed emergence of neuropsychiatric symptoms. In this pilot project we studied former National Football League (NFL) players using new neuroimaging techniques and clinical measures of cognitive functioning. We hypothesized that former NFL players would show molecular and structural changes in medial temporal and parietal lobe structures as well as specific cognitive deficits, namely those of verbal learning and memory. We observed a significant increase in binding of [(11)C]DPA-713 to the translocator protein (TSPO), a marker of brain injury and repair, in several brain regions, such as the supramarginal gyrus and right amygdala, in 9 former NFL players compared to 9 age-matched, healthy controls. We also observed significant atrophy of the right hippocampus. Finally, we report that these same former players had varied performance on a test of verbal learning and memory, suggesting that these molecular and pathologic changes may play a role in cognitive decline. These results suggest that localized brain injury and repair, indicated by increased [(11)C]DPA-713 binding to TSPO, may be linked to history of NFL play. [(11)C]DPA-713 PET is a promising new tool that can be used in future study design to examine further the relationship between TSPO expression in brain injury and repair, selective regional brain atrophy, and the potential link to

  18. Clinical significance of ventricular enlargement and cortical atrophy in computed tomography of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Busse, O.; Agnoli, A.L.; Lippmann, R.; Schuetz, H.J.

    1981-02-01

    The diagnosis of atrophy of the brain based on the visual interpretation of CT findings appears questionable. In 56 patients there was no correlation between the CT findings of enlarged ventricles and sulci and clinical findings of psychoorganic syndromes. Only the group of 60 to 80 year old patients showed a statistically significant correlation between psychoorganic findings and the area of the lateral ventricles - measured planimetrically - and the diameter of the cella medica, but not the group of the 40 to 60 year old. There was no relationship between the number of cortical sulci and psychopathology. The morphological findings of ventricular enlargement and cortical atrophy in CT - even with exact measurements - do not allow any conclusions in regard to psychoorganic findings.

  19. 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.

  20. A putative Alzheimer's disease risk allele in PCK1 influences brain atrophy in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Zongqi Xia

    2010-11-01

    Full Text Available Brain atrophy and cognitive dysfunction are neurodegenerative features of Multiple Sclerosis (MS. We used a candidate gene approach to address whether genetic variants implicated in susceptibility to late onset Alzheimer's Disease (AD influence brain volume and cognition in MS patients.MS subjects were genotyped for five single nucleotide polymorphisms (snps associated with susceptibility to AD: PICALM, CR1, CLU, PCK1, and ZNF224. We assessed brain volume using Brain Parenchymal Fraction (BPF measurements obtained from Magnetic Resonance Imaging (MRI data and cognitive function using the Symbol Digit Modalities Test (SDMT. Genotypes were correlated with cross-sectional BPF and SDMT scores using linear regression after adjusting for sex, age at symptom onset, and disease duration. 722 MS patients with a mean (±SD age at enrollment of 41 (±10 years were followed for 44 (±28 months. The AD risk-associated allele of a non-synonymous SNP in the PCK1 locus (rs8192708G is associated with a smaller average brain volume (P=0.0047 at the baseline MRI, but it does not impact our baseline estimate of cognition. PCK1 is additionally associated with higher baseline T2-hyperintense lesion volume (P=0.0088. Finally, we provide technical validation of our observation in a subset of 641 subjects that have more than one MRI study, demonstrating the same association between PCK1 and smaller average brain volume (P=0.0089 at the last MRI visit.Our study provides suggestive evidence for greater brain atrophy in MS patients bearing the PCK1 allele associated with AD-susceptibility, yielding new insights into potentially shared neurodegenerative process between MS and late onset AD.

  1. Auditory brain-stem responses in adrenomyeloneuropathy.

    Science.gov (United States)

    Grimes, A M; Elks, M L; Grunberger, G; Pikus, A M

    1983-09-01

    We studied three patients with adrenomyeloneuropathy. Complete audiologic assessment was obtained: two patients showed unimpaired peripheral hearing and one showed a mild high-frequency hearing loss. Auditory brain-stem responses were abnormal in both ears of all subjects, with one subject showing no response above wave I, and the other two having significant wave I to III and wave III to V interval prolongations. We concluded that auditory brain-stem response testing provides a simple, valid, reliable method for demonstrating neurologic abnormality in adrenomyeloneuropathy even prior to evidence of clinical signs.

  2. Vascular brain lesions, brain atrophy, and cognitive decline. The Second Manifestations of ARTerial diseased-Magnetic Resonance (SMART-MR) study

    NARCIS (Netherlands)

    Kooistra, M.; Geerlings, M.I.; van der Graaf, Y.; Mali, W.P.T.M.; Vincken, K.L.; Kappelle, L.J.; Muller, M.; Biessels, G.J.

    2014-01-01

    We examined the association between brain atrophy and vascular brain lesions (i.e., white matter lesions [WMLs] or brain infarcts), alone or in combination, with decline in memory and executive functioning over 4 years of follow-up in 448 patients (57 ± 9.5 years) with symptomatic atherosclerotic

  3. CT features of olivopontocerebellar atrophy in children

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S.D. [Sultan Qaboos Univ., Muscat (Oman). Dept. of Radiology; Chand, R.P. [Sultan Qaboos Univ., Muscat (Oman). Dept. of Medicine (Neurology); Gururaj, A.K. [Sultan Qaboos Univ., Muscat (Oman). Dept. of Child Health; Jeans, W.D. [Sultan Qaboos Univ., Muscat (Oman). Dept. of Radiology

    1995-11-01

    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.).

  4. Progression of brain atrophy in spinocerebellar ataxia type 2: a longitudinal tensor-based morphometry study.

    Directory of Open Access Journals (Sweden)

    Mario Mascalchi

    Full Text Available Spinocerebellar ataxia type 2 (SCA2 is the second most frequent autosomal dominant inherited ataxia worldwide. We investigated the capability of magnetic resonance imaging (MRI to track in vivo progression of brain atrophy in SCA2 by examining twice 10 SCA2 patients (mean interval 3.6 years and 16 age- and gender-matched healthy controls (mean interval 3.3 years on the same 1.5 T MRI scanner. We used T1-weighted images and tensor-based morphometry (TBM to investigate volume changes and the Inherited Ataxia Clinical Rating Scale to assess the clinical deficit. With respect to controls, SCA2 patients showed significant higher atrophy rates in the midbrain, including substantia nigra, basis pontis, middle cerebellar peduncles and posterior medulla corresponding to the gracilis and cuneatus tracts and nuclei, cerebellar white matter (WM and cortical gray matter (GM in the inferior portions of the cerebellar hemisphers. No differences in WM or GM volume loss were observed in the supratentorial compartment. TBM findings did not correlate with modifications of the neurological deficit. In conclusion, MRI volumetry using TBM is capable of demonstrating the progression of pontocerebellar atrophy in SCA2, supporting a possible role of MRI as biomarker in future trials.

  5. Brain stem and cerebellum volumetric analysis of Machado Joseph disease patients

    Directory of Open Access Journals (Sweden)

    S T Camargos

    2011-01-01

    Full Text Available Machado-Joseph disease, or spinocerebellar ataxia type 3(MJD/SCA3, is the most frequent late onset spinocerebellar ataxia and results from a CAG repeat expansion in the ataxin-3 gene. Previous studies have found correlation between atrophy of cerebellum and brainstem with age and CAG repeats, although no such correlation has been found with disease duration and clinical manifestations. In this study we test the hypothesis that atrophy of cerebellum and brainstem in MJD/SCA3 is related to clinical severity, disease duration and CAG repeat length as well as to other variables such as age and ICARS (International Cooperative Ataxia Rating Scale. Whole brain high resolution MRI and volumetric measurement with cranial volume normalization were obtained from 15 MJD/SCA3 patients and 15 normal, age and sex-matchedcontrols. We applied ICARS and compared the score with volumes and CAG number, disease duration and age. We found significant correlation of both brain stem and cerebellar atrophy with CAG repeat length, age, disease duration and degree of disability. The Spearman rank correlation was stronger with volumetric reduction of the cerebellum than with brain stem. Our data allow us to conclude that volumetric analysis might reveal progressive degeneration after disease onset, which in turn is linked to both age and number of CAG repeat expansions in SCA 3.

  6. Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Dhruv Sareen

    Full Text Available Spinal muscular atrophy (SMA is a genetic disorder caused by a deletion of the survival motor neuron 1 gene leading to motor neuron loss, muscle atrophy, paralysis, and death. We show here that induced pluripotent stem cell (iPSC lines generated from two Type I SMA subjects-one produced with lentiviral constructs and the second using a virus-free plasmid-based approach-recapitulate the disease phenotype and generate significantly fewer motor neurons at later developmental time periods in culture compared to two separate control subject iPSC lines. During motor neuron development, both SMA lines showed an increase in Fas ligand-mediated apoptosis and increased caspase-8 and-3 activation. Importantly, this could be mitigated by addition of either a Fas blocking antibody or a caspase-3 inhibitor. Together, these data further validate this human stem cell model of SMA, suggesting that specific inhibitors of apoptotic pathways may be beneficial for patients.

  7. Objectively measured physical activity, brain atrophy, and white matter lesions in older adults with mild cognitive impairment.

    Science.gov (United States)

    Doi, Takehiko; Makizako, Hyuma; Shimada, Hiroyuki; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Park, Hyuntae; Suzuki, Takao

    2015-02-01

    Physical activity may help to prevent or delay brain atrophy. Numerous studies have shown associations between physical activity and age-related changes in the brain. However, most of these studies involved self-reported physical activity, not objectively measured physical activity. Therefore, the aim of this study was to examine the association between objectively measured physical activity, as determined using accelerometers, and brain magnetic resonance imaging (MRI) measures in older adults with mild cognitive impairment (MCI). We analyzed 323 older subjects with MCI (mean age 71.4 years) who were recruited from the participants of the Obu Study of Health Promotion for the Elderly. We recorded demographic data and measured physical activity using a tri-axial accelerometer. Physical activity was classified as light-intensity physical activity (LPA) or moderate-to-vigorous physical activity (MVPA). Brain atrophy and the severity of white matter lesions (WML) were determined by MRI. Low levels of LPA and MVPA were associated with severe WML. Subjects with severe WML were older, had lower mobility, and had greater brain atrophy than subjects with mild WML (all Pactivity, especially MVPA, was associated with brain atrophy in MCI subjects, even after adjusting for WML. These findings support the hypothesis that physical activity plays a crucial role in maintaining brain health. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Magnetic resonance volumetry reveals focal brain atrophy in transient epileptic amnesia.

    Science.gov (United States)

    Butler, Christopher; van Erp, Willemijn; Bhaduri, Amit; Hammers, Alexander; Heckemann, Rolf; Zeman, Adam

    2013-09-01

    Transient epileptic amnesia (TEA) is a recently described epilepsy syndrome characterized by recurrent episodes of isolated memory loss. It is associated with two unusual forms of interictal memory impairment: accelerated long-term forgetting (ALF) and autobiographical amnesia. We investigated the neural basis of TEA using manual volumetry and automated multi-atlas-based segmentation of whole-brain magnetic resonance imaging data from 40 patients with TEA and 20 healthy controls. Both methods confirmed the presence of subtle, bilateral hippocampal atrophy. Additional atrophy was revealed in perirhinal and orbitofrontal cortices. The volumes of these regions correlated with anterograde memory performance. No structural correlates were found for ALF or autobiographical amnesia. The results support the hypothesis that TEA is a focal medial temporal lobe epilepsy syndrome but reveal additional pathology in connected brain regions. The unusual interictal memory deficits of TEA remain unexplained by structural pathology and may reflect physiological disruption of memory networks by subclinical epileptiform activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Association of white-matter lesions with brain atrophy markers: the three-city Dijon MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Godin, O.; Alperovitch, A.; Tzourio, Ch.; Dufouil, C. [Inserm U708 ' Neuroepidemiology' , Paris (France); Godin, O.; Alperovitch, A.; Tzourio, Ch.; Dufouil, C. [UPMC University Paris 6 (France); Mazoyer, B. [Institut Universitaire de France, Paris (France); Maillard, P.; Crivello, F.; Mazoyer, B. [CNRS, CI-NAPS UMR6232 (France); Maillard, P.; Crivello, F.; Mazoyer, B. [CEA, DSV/I2BM/CI-NAPS (France); Maillard, P.; Crivello, F.; Mazoyer, B. [Universite de Caen Basse-Normande (France); Mazoyer, B. [Centre Hospitalier et Universitaire de Caen, Caen (France)

    2009-07-01

    Background: Brain atrophy and white-matter lesions (WML) are common features at cerebral MRI of both normal and demented elderly people. In a population-based study of 1, 792 elderly subjects aged 65-80 years, free of dementia, who had a cerebral MRI at entry, we investigated the relationship between WML volume and brain atrophy markers estimated by hippocampal, gray matter (GM) and cerebrospinal fluid (CSF) volumes. Methods: An automated algorithm of detection and quantification of WML was developed, and voxel-based morphometry methods were used to estimate GM, CSF and hippocampal volumes. To evaluate the relation between those volumes and WML load, we used analysis of covariance and multiple linear regression models adjusting for potential confounders and total intracranial volumes. Results: Age was highly correlated with WML load and all brain atrophy markers. Total WML volume was negatively associated with both GM ({beta} = -0.03, p {<=} 0.0001) and hippocampal volumes ({beta} = -0.75, p = 0.0009) and positively with CSF volumes (beta 0.008, p = 0.02) after controlling for sex, age, education level, hypertension and apolipoprotein E genotype. Evidence for a relationship between brain atrophy markers and WML was stronger for periventricular WML. We found that the relationship between WML and hippocampal volumes was independent of other brain tissue volumes. Conclusion: These results suggest that, in the brain of non demented elderly subjects, degenerative processes and vascular changes co-occur and are related independently of vascular risk factors. (authors)

  10. Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy Magnetic Resonance Imaging Measurements in Alzheimer's Disease.

    Science.gov (United States)

    Bilello, Michel; Doshi, Jimit; Nabavizadeh, S Ali; Toledo, Jon B; Erus, Guray; Xie, Sharon X; Trojanowski, John Q; Han, Xiaoyan; Davatzikos, Christos

    2015-01-01

    Vascular risk factors are increasingly recognized as risks factors for Alzheimer's disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function, or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly.

  11. Contribution of brain atrophy on CT and aging to intelligence level. A clonological study through multivariate analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Makoto (Showa Univ., Tokyo (Japan). School of Medicine)

    1984-09-01

    Decrased intellectual functions due to senility have been much discussed in connection with aging or brain atrophy alternatively. But this change should be analysed under multifactorial basis. Furthermore, variations between individuals should be taken into account in dealing with an advanced age group. In these regards, the author performed multivariate analysis on intellectual changes, aging and brain atrophy demonstrated on brain CT. Clonological study was also performed to reveal the individual variations. The objects were consisted of 72 people, including the patients of more than 65 years of age who were hospitalized to a geriatrics hospital because of senile dementia, and, as a control group residents in a home for the aged nearby the hospital. Average age was 75.4 years old. Intellectual level was measured through Hasegawa's dementia rating scale. Ventricular enlargement was measured on brain CT to determine the severity of brain atrophy. These two factors and age were processed with multivariate analysis. And chronological study was made to the deviation of intellectual level vs. the change of ventricular enlargement. As the result, firstly, this simple analysing model was able to reveal some aspects of the deteriorating phenomena of intellectual level through double factorial basis, i.e. brain atrophy on CT and age. Secondly, the group showing greater changes in the brain atrophy on CT, which included one case with rapid deterioration in dementia scale of more than 10 points, was distributed mainly around full marks or zero point in dementia scale. This result postulates that the range of the dementia scale should be expanded upwrds as well as downwards for the better explanation of the relation between intellectual deterioration and above mentioned two factors.

  12. Whole-brain atrophy differences between progressive supranuclear palsy and idiopathic Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Carlos Guevara

    2016-09-01

    Full Text Available Background: The absence of markers for ante-mortem diagnosis of progressive supranuclear palsy (PSP results in this disorder’s being commonly mistaken for other conditions, such as idiopathic Parkinson's disease (IPD. Such mistakes occur particularly in the initial stages, when ‘plus syndrome’ has not yet clinically emerged.Objective. To investigate global brain volume and tissue loss in patients with PSP relative to patients with IPD and healthy controls and correlations between clinical parameters and magnetic resonance imaging (MRI-derived brain volume estimates.Methods: T1-weighted images were obtained from three groups of Chilean Latin American adults: 21 patients with IPD, 18 patients with PSP and 14 healthy controls. We used Structural Imaging Evaluation with Normalization of Atrophy (SIENAX to assess white matter, gray matter and whole-brain volumes (normalized to cranial volume. Imaging data were used to analyze putative correlations with the clinical status of PSP and IPD patients using the Unified Parkinson’s Disease Rating Scale Part III, Hoehn and Yahr, the Clinical Global Impression for Disease Severity Scale and the Frontal Assessment Battery.Results: PSP patients had significantly lower whole brain volume than both IPD patients and controls. Whole brain volume reduction in PSP patients was primarily attributable to gray matter volume reduction. We found a significant correlation between brain volume reduction and clinical status in the PSP group.Conclusions: At the group level, whole brain and gray matter volumes differentiated patients with PSP from patients with IPD. There was also significant clinical-imaging correlations with motor disturbances in PSP.

  13. Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment

    Science.gov (United States)

    Ahmed, Mohamed; Cannon, Dara M; Scanlon, Cathy; Holleran, Laurena; Schmidt, Heike; McFarland, John; Langan, Camilla; McCarthy, Peter; Barker, Gareth J; Hallahan, Brian; McDonald, Colm

    2015-01-01

    Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6–9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity. PMID:25829144

  14. Quantitative assessment of MS plaques and brain atrophy in multiple sclerosis using semiautomatic segmentation method

    Science.gov (United States)

    Heinonen, Tomi; Dastidar, Prasun; Ryymin, Pertti; Lahtinen, Antti J.; Eskola, Hannu; Malmivuo, Jaakko

    1997-05-01

    Quantitative magnetic resonance (MR) imaging of the brain is useful in multiple sclerosis (MS) in order to obtain reliable indices of disease progression. The goal of this project was to estimate the total volume of gliotic and non gliotic plaques in chronic progressive multiple sclerosis with the help of a semiautomatic segmentation method developed at the Ragnar Granit Institute. Youth developed program running on a PC based computer provides de displays of the segmented data, in addition to the volumetric analyses. The volumetric accuracy of the program was demonstrated by segmenting MR images of fluid filed syringes. An anatomical atlas is to be incorporated in the segmentation system to estimate the distribution of MS plaques in various neural pathways of the brain. A total package including MS plaque volume estimation, estimation of brain atrophy and ventricular enlargement, distribution of MS plaques in different neural segments of the brain has ben planned for the near future. Our study confirmed that total lesion volumes in chronic MS disease show a poor correlation to EDSS scores but show a positive correlation to neuropsychological scores. Therefore accurate total volume measurements of MS plaques using the developed semiautomatic segmentation technique helped us to evaluate the degree of neuropsychological impairment.

  15. Neurocognitive functions and brain atrophy after proven neuroborreliosis: a case-control study.

    Science.gov (United States)

    Schmidt, Holger; Djukic, Marija; Jung, Klaus; Holzgraefe, Manfred; Dechent, Peter; von Steinbüchel, Nicole; Blocher, Joachim; Eiffert, Helmut; Schmidt-Samoa, Carsten

    2015-08-19

    Patients often report neurocognitive difficulties after neuroborreliosis (NB). The frequency and extent of cognitive problems in European patients have been studied incompletely. Sixty patients received a neurological and neuropsychological work-up 6 months or longer after treatment for proven NB. Quality of life, psychiatric symptom load, and brain atrophy were measured. All results were compared with a group of 30 healthy control persons adapted for age, gender and education being serologically negative for Borrelia burgdorferi senso latu. A cognitive sum score and a global sum score including cognitive, psychological results and quality of life data was calculated for both groups. Patients after NB showed a lower (i.e. more impaired) score on the Scripps Neurological rating scale (SNRS), but the observed neurological deficits were generally mild (mean ± SD: 97.1 ± 4.7 vs. 99.1 ± 2.4, p = 0.02). The mean neuropsychological domain results of the NB group were all within the normal range. However, a lower performance was found for the frontal executive function z-values (mean ± SD -0.29 ± 0.60 vs. 0.09 ± 0.60; p = 0.0059) of NB patients. Comparing the global sum score (mean ± SD 11.3 ± 4.2 NB vs. 14.3 ± 2.9 control , p = 0.001) and the cognitive sum score of the NB group with those of the control group (mean ± SD -0.15 ± 0.42 NB vs. 0.08 ± 0.31 control , p = 0.0079), both differences were statistically different. The frequencies of impaired global sum scores and those of the pathological cognitive sum scores (p = 0.07) did not differ statistically. No significant differences were found for health-related quality of life (hrQoL), sleep, psychiatric symptom load, or brain atrophy. The mean cognitive functions of patients after proven NB were in the normal range. However, we were able to demonstrate a lower performance for the domain of frontal executive functions, for the mean cognitive sum score and the global sum score as a sign of subtle but measurable

  16. Revisiting Brain Atrophy and Its Relationship to Disability in Multiple Sclerosis

    Science.gov (United States)

    Shiee, Navid; Bazin, Pierre-Louis; Zackowski, Kathleen M.; Farrell, Sheena K.; Harrison, Daniel M.; Newsome, Scott D.; Ratchford, John N.; Caffo, Brian S.; Calabresi, Peter A.; Pham, Dzung L.; Reich, Daniel S.

    2012-01-01

    Background Brain atrophy is a well-accepted imaging biomarker of multiple sclerosis (MS) that partially correlates with both physical disability and cognitive impairment. Methodology/Principal Findings Based on MRI scans of 60 MS cases and 37 healthy volunteers, we measured the volumes of white matter (WM) lesions, cortical gray matter (GM), cerebral WM, caudate nucleus, putamen, thalamus, ventricles, and brainstem using a validated and completely automated segmentation method. We correlated these volumes with the Expanded Disability Status Scale (EDSS), MS Severity Scale (MSSS), MS Functional Composite (MSFC), and quantitative measures of ankle strength and toe sensation. Normalized volumes of both cortical and subcortical GM structures were abnormally low in the MS group, whereas no abnormality was found in the volume of the cerebral WM. High physical disability was associated with low cerebral WM, thalamus, and brainstem volumes (partial correlation coefficients ∼0.3–0.4) but not with low cortical GM volume. Thalamus volumes were inversely correlated with lesion load (r = −0.36, p<0.005). Conclusion The GM is atrophic in MS. Although lower WM volume is associated with greater disability, as might be expected, WM volume was on average in the normal range. This paradoxical result might be explained by the presence of coexisting pathological processes, such as tissue damage and repair, that cause both atrophy and hypertrophy and that underlie the observed disability. PMID:22615886

  17. Revisiting brain atrophy and its relationship to disability in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Navid Shiee

    Full Text Available Brain atrophy is a well-accepted imaging biomarker of multiple sclerosis (MS that partially correlates with both physical disability and cognitive impairment.Based on MRI scans of 60 MS cases and 37 healthy volunteers, we measured the volumes of white matter (WM lesions, cortical gray matter (GM, cerebral WM, caudate nucleus, putamen, thalamus, ventricles, and brainstem using a validated and completely automated segmentation method. We correlated these volumes with the Expanded Disability Status Scale (EDSS, MS Severity Scale (MSSS, MS Functional Composite (MSFC, and quantitative measures of ankle strength and toe sensation. Normalized volumes of both cortical and subcortical GM structures were abnormally low in the MS group, whereas no abnormality was found in the volume of the cerebral WM. High physical disability was associated with low cerebral WM, thalamus, and brainstem volumes (partial correlation coefficients ~0.3-0.4 but not with low cortical GM volume. Thalamus volumes were inversely correlated with lesion load (r = -0.36, p<0.005.The GM is atrophic in MS. Although lower WM volume is associated with greater disability, as might be expected, WM volume was on average in the normal range. This paradoxical result might be explained by the presence of coexisting pathological processes, such as tissue damage and repair, that cause both atrophy and hypertrophy and that underlie the observed disability.

  18. Transcriptome profiling of spinal muscular atrophy motor neurons derived from mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Miho Maeda

    Full Text Available Proximal spinal muscular atrophy (SMA is an early onset, autosomal recessive motor neuron disease caused by loss of or mutation in SMN1 (survival motor neuron 1. Despite understanding the genetic basis underlying this disease, it is still not known why motor neurons (MNs are selectively affected by the loss of the ubiquitously expressed SMN protein. Using a mouse embryonic stem cell (mESC model for severe SMA, the RNA transcript profiles (transcriptomes between control and severe SMA (SMN2+/+;mSmn-/- mESC-derived MNs were compared in this study using massively parallel RNA sequencing (RNA-Seq. The MN differentiation efficiencies between control and severe SMA mESCs were similar. RNA-Seq analysis identified 3,094 upregulated and 6,964 downregulated transcripts in SMA mESC-derived MNs when compared against control cells. Pathway and network analysis of the differentially expressed RNA transcripts showed that pluripotency and cell proliferation transcripts were significantly increased in SMA MNs while transcripts related to neuronal development and activity were reduced. The differential expression of selected transcripts such as Crabp1, Crabp2 and Nkx2.2 was validated in a second mESC model for SMA as well as in the spinal cords of low copy SMN2 severe SMA mice. Furthermore, the levels of these selected transcripts were restored in high copy SMN2 rescue mouse spinal cords when compared against low copy SMN2 severe SMA mice. These findings suggest that SMN deficiency affects processes critical for normal development and maintenance of MNs.

  19. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    Background: Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. Nowadays, it is increasingly believed that gliomas may arise from cancer stem cells, which share several characteristics with normal neural stem cells. Brain tumor stem cells have been found to express a ...

  20. Discriminant Analysis of Intracranial Volumetric Variables in Patients with Normal Pressure Hydrocephalus and Brain Atrophy.

    Science.gov (United States)

    Czerwosz, Leszek; Szczepek, Ewa; Nowiński, Krzysztof; Sokołowska, Beata; Jurkiewicz, Jerzy; Czernicki, Zbigniew; Koszewski, Waldemar

    2018-01-01

    A method was developed for the computerized volumetric assessment of the intracranial cerebrospinal fluid (CSF) distribution. The study involved 62 patients differentiated into two groups: with CSF resorption disorders (normal pressure hydrocephalus - 30 patients) and without CSF resorption disorders (various types of brain atrophy - 32 patients). The goal of the study was to ascertain whether the assessment, depending on the linear discriminant analysis of volumetric brain features, could be an effective tool differentiating the two groups. Volumetric measurements were performed using VisNow software. For each patient, five features were determined and subjected to discriminant analysis: CSF volume in the subarachnoid space and basal cisterns (SV), CSF volume in the intracranial ventricular system (VV), brain volume (BV), total intracranial CSF volume (FV), and total intracranial volume (TV). Discriminant analysis enables the achievement of a high percentage of correct classification of patients to the appropriate group determined on the result of a lumbar infusion test. The discriminator, based on three features: BV, SV, and VV, showed a complete separation of the groups; irrespective of age. The squared Mahalanobis distance was 70.8. The results confirmed the applicability of the volumetric method. Discriminant analysis seems a useful tool leading to the acquisition of a computer-aided method for the differential diagnosis of CSF resorption disorders.

  1. Computed tomographic (CT) study of the brains of 357 elderly demented patients. Clinical usefulness of CT measurements of brain atrophy and its correlation with mental assessment

    Energy Technology Data Exchange (ETDEWEB)

    Kono, Kazuhiko; Endo, Hidetoshi; Yamamoto, Takayuki; Kuzuya, Fumio

    1988-05-01

    It is well known that there is some limitation in the diagnostic effectiveness of brain computed tomography (CT) of dementia. Some investigators suggested certain correlation between brain atrophy and degree of psychological imparement in demented patients, but others did not agree with these suggestions. Authors have felt that the number of samples is very important in statistical analyses, thus they collected a great number of appropriate samples of dementia: that is, 59 of Alzheimer disease (AD), 120 of senile dementia of Alzheimer type (SDAT) and 178 of vascular dementia (VD), and compared these CT findings with those of 100 non-demented people. Firstly, we observed no relation between aging and brain atrophy in any type of dementia while there was a certain relation in non-demented people. Secondly, the female brain could easily become atrophic physiologically and was more severely atrophic in case of dementia compared with the male brain. Thirdly, it was impossible to differentiate SDAT from VD only by measuring values of dilatation of ventricles (maximum width of the third ventricle and cella media index) and sylvian fissures (''sylvian index''). Finally, it was observed that there was deep relation between the results of clinical assessments and the degree of brain atrophy in SDAT, because individual specificity in the type of atrophy was not variable in this type of dementia. Moreover all functions: that is, motor, intellectual, and emotional functions in SDAT patients, were impaired in the same degree respectively. From these results, authors could know many available characteristics of atrophy in the brains of demented patients through the following easy methods of measurement: linear measure method and ventricular-brain method, because we could analyse a sufficient number of samples.

  2. Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults.

    Science.gov (United States)

    Risacher, Shannon L; McDonald, Brenna C; Tallman, Eileen F; West, John D; Farlow, Martin R; Unverzagt, Fredrick W; Gao, Sujuan; Boustani, Malaz; Crane, Paul K; Petersen, Ronald C; Jack, Clifford R; Jagust, William J; Aisen, Paul S; Weiner, Michael W; Saykin, Andrew J

    2016-06-01

    The use of anticholinergic (AC) medication is linked to cognitive impairment and an increased risk of dementia. To our knowledge, this is the first study to investigate the association between AC medication use and neuroimaging biomarkers of brain metabolism and atrophy as a proxy for understanding the underlying biology of the clinical effects of AC medications. To assess the association between AC medication use and cognition, glucose metabolism, and brain atrophy in cognitively normal older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Indiana Memory and Aging Study (IMAS). The ADNI and IMAS are longitudinal studies with cognitive, neuroimaging, and other data collected at regular intervals in clinical and academic research settings. For the participants in the ADNI, visits are repeated 3, 6, and 12 months after the baseline visit and then annually. For the participants in the IMAS, visits are repeated every 18 months after the baseline visit (402 cognitively normal older adults in the ADNI and 49 cognitively normal older adults in the IMAS were included in the present analysis). Participants were either taking (hereafter referred to as the AC+ participants [52 from the ADNI and 8 from the IMAS]) or not taking (hereafter referred to as the AC- participants [350 from the ADNI and 41 from the IMAS]) at least 1 medication with medium or high AC activity. Data analysis for this study was performed in November 2015. Cognitive scores, mean fludeoxyglucose F 18 standardized uptake value ratio (participants from the ADNI only), and brain atrophy measures from structural magnetic resonance imaging were compared between AC+ participants and AC- participants after adjusting for potential confounders. The total AC burden score was calculated and was related to target measures. The association of AC use and longitudinal clinical decline (mean [SD] follow-up period, 32.1 [24.7] months [range, 6-108 months]) was examined using Cox regression. The

  3. Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults

    Science.gov (United States)

    Risacher, Shannon L.; McDonald, Brenna C.; Tallman, Eileen F.; West, John D.; Farlow, Martin R.; Unverzagt, Fredrick W.; Gao, Sujuan; Boustani, Malaz; Crane, Paul K.; Petersen, Ronald C.; Jack, Clifford R.; Jagust, William J.; Aisen, Paul S.; Weiner, Michael W.; Saykin, Andrew J.

    2016-01-01

    IMPORTANCE The use of anticholinergic (AC) medication is linked to cognitive impairment and an increased risk of dementia. To our knowledge, this is the first study to investigate the association between AC medication use and neuroimaging biomarkers of brain metabolism and atrophy as a proxy for understanding the underlying biology of the clinical effects of AC medications. OBJECTIVE To assess the association between AC medication use and cognition, glucose metabolism, and brain atrophy in cognitively normal older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Indiana Memory and Aging Study (IMAS). DESIGN, SETTING, AND PARTICIPANTS The ADNI and IMAS are longitudinal studies with cognitive, neuroimaging, and other data collected at regular intervals in clinical and academic research settings. For the participants in the ADNI, visits are repeated 3, 6, and 12 months after the baseline visit and then annually. For the participants in the IMAS, visits are repeated every 18 months after the baseline visit (402 cognitively normal older adults in the ADNI and 49 cognitively normal older adults in the IMAS were included in the present analysis). Participants were either taking (hereafter referred to as the AC+ participants [52 from the ADNI and 8 from the IMAS]) or not taking (hereafter referred to as the AC− participants [350 from the ADNI and 41 from the IMAS]) at least 1 medication with medium or high AC activity. Data analysis for this study was performed in November 2015. MAIN OUTCOMES AND MEASURES Cognitive scores, mean fludeoxyglucose F 18 standardized uptake value ratio (participants from the ADNI only), and brain atrophy measures from structural magnetic resonance imaging were compared between AC+ participants and AC− participants after adjusting for potential confounders. The total AC burden score was calculated and was related to target measures. The association of AC use and longitudinal clinical decline (mean [SD] follow

  4. Generation of sibling-matched induced pluripotent stem cell lines from spinal and bulbar muscular atrophy patients

    Directory of Open Access Journals (Sweden)

    Gunaseelan Narayanan

    2017-04-01

    Full Text Available Spinal and bulbar muscular atrophy (SBMA is a neurodegenerative disease caused by the expansion of CAG repeats in the Androgen Receptor gene (AR. We report the generation of induced pluripotent stem cell (iPSC lines from two SBMA patients and their healthy siblings. The SBMA and healthy iPSC lines retain the number of AR CAG repeats, express pluripotency markers and are able to differentiate into the three germ layers. The iPSC lines are also free of Sendai virus transgenes and have normal karyotypes. The SBMA iPSC lines with their sibling-matched controls would serve as useful tools to study SBMA disease mechanism.

  5. Delineating SPTAN1 associated phenotypes: from isolated epilepsy to encephalopathy with progressive brain atrophy.

    Science.gov (United States)

    Syrbe, Steffen; Harms, Frederike L; Parrini, Elena; Montomoli, Martino; Mütze, Ulrike; Helbig, Katherine L; Polster, Tilman; Albrecht, Beate; Bernbeck, Ulrich; van Binsbergen, Ellen; Biskup, Saskia; Burglen, Lydie; Denecke, Jonas; Heron, Bénédicte; Heyne, Henrike O; Hoffmann, Georg F; Hornemann, Frauke; Matsushige, Takeshi; Matsuura, Ryuki; Kato, Mitsuhiro; Korenke, G Christoph; Kuechler, Alma; Lämmer, Constanze; Merkenschlager, Andreas; Mignot, Cyril; Ruf, Susanne; Nakashima, Mitsuko; Saitsu, Hirotomo; Stamberger, Hannah; Pisano, Tiziana; Tohyama, Jun; Weckhuysen, Sarah; Werckx, Wendy; Wickert, Julia; Mari, Francesco; Verbeek, Nienke E; Møller, Rikke S; Koeleman, Bobby; Matsumoto, Naomichi; Dobyns, William B; Battaglia, Domenica; Lemke, Johannes R; Kutsche, Kerstin; Guerrini, Renzo

    2017-09-01

    De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1 mutations. Using different molecular genetic techniques, we identified 20 patients with a pathogenic or likely pathogenic SPTAN1 variant and reviewed their clinical, genetic and imaging data. SPTAN1 de novo alterations included seven unique missense variants and nine in-frame deletions/duplications of which 12 were novel. The recurrent three-amino acid duplication p.(Asp2303_Leu2305dup) occurred in five patients. Our patient cohort exhibited a broad spectrum of neurodevelopmental phenotypes, comprising six patients with mild to moderate intellectual disability, with or without epilepsy and behavioural disorders, and 14 patients with infantile epileptic encephalopathy, of which 13 had severe neurodevelopmental impairment and four died in early childhood. Imaging studies suggested that the severity of neurological impairment and epilepsy correlates with that of structural abnormalities as well as the mutation type and location. Out of seven patients harbouring mutations outside the α/β spectrin heterodimerization domain, four had normal brain imaging and three exhibited moderately progressive brain and/or cerebellar atrophy. Twelve of 13 patients with mutations located within the spectrin heterodimer contact site exhibited severe and progressive brain, brainstem and cerebellar atrophy, with hypomyelination in most. We used fibroblasts from five patients to study spectrin aggregate formation by Triton-X extraction and immunocytochemistry followed by fluorescence microscopy. αII/βII aggregates and αII spectrin in the insoluble protein fraction were observed in fibroblasts derived from patients with the mutations p.(Glu2207del), p.(Asp2303_Leu2305dup) and p.(Arg2308_Met2309dup

  6. Presymptomatic generalized brain atrophy in frontotemporal dementia caused by CHMP2B mutation

    DEFF Research Database (Denmark)

    Rohrer, Jonathan D; Ahsan, R Laila; Isaacs, Adrian M

    2009-01-01

    BACKGROUND/AIMS: CHMP2B mutations are a rare cause of familial frontotemporal dementia (FTD). The clinical syndrome is dominated by personality change and behavioural symptoms, but language, memory, calculation and praxis impairments are also seen early in the course of the disease. There are no ......BACKGROUND/AIMS: CHMP2B mutations are a rare cause of familial frontotemporal dementia (FTD). The clinical syndrome is dominated by personality change and behavioural symptoms, but language, memory, calculation and praxis impairments are also seen early in the course of the disease....... There are no detailed studies of brain imaging in CHMP2B mutation-associated FTD. This study aimed to investigate whether there were early or presymptomatic changes in this group of patients. METHODS: Subjects comprised 16 members of a Danish family with CHMP2B mutation-associated FTD. Nine subjects were presymptomatic...... mutation carriers with a control group of 7 mutation-negative family members. Volumetric MRI brain scans were performed on all subjects at two time points, and rates of volume change were compared between the two groups. RESULTS: We demonstrate that generalized atrophy occurs presymptomatically in CHMP2B...

  7. Brain atrophy and neuropsychological outcome after treatment of ruptured anterior cerebral artery aneurysms: a voxel-based morphometric study

    Energy Technology Data Exchange (ETDEWEB)

    Bendel, Paula; Koskenkorva, Paeivi; Vanninen, Ritva [Kuopio University Hospital and University of Kuopio, Department of Clinical Radiology, Kuopio (Finland); Koivisto, Timo; Aeikiae, Marja [Kuopio University Hospital and University of Kuopio, Department of Neurosurgery, Kuopio (Finland); Niskanen, Eini [Kuopio University Hospital and University of Kuopio, Department of Neurology, Kuopio (Finland); Kuopio University Hospital and University of Kuopio, Department of Physics, Kuopio (Finland); Koenoenen, Mervi [Kuopio University Hospital and University of Kuopio, Department of Clinical Radiology, Kuopio (Finland); Kuopio University Hospital and University of Kuopio, Department of Clinical Neurophysiology, Kuopio (Finland); Haenninen, Tuomo [Kuopio University Hospital and University of Kuopio, Department of Neurology, Kuopio (Finland)

    2009-11-15

    Cognitive impairment after aneurysmal subarachnoid hemorrhage (aSAH) is frequently detected. Here, we describe the pattern of cerebral (gray matter) atrophy and its clinical relevance after treatment of aSAH caused by a ruptured anterior cerebral artery (ACA) aneurysm. Thirty-seven aSAH patients with ACA aneurysm (17 surgical, 20 endovascular treatment) and a good or moderate clinical outcome (Glasgow Outcome Scale V or IV) and 30 controls underwent brain MRI. Voxel-based morphometric analysis was applied to compare the patients and controls. Patients also underwent a detailed neuropsychological assessment. The comparisons between controls and either all patients (n=37) or the subgroup of surgically treated patients (n=17) revealed bilateral cortical atrophy in the frontal lobes, mainly in the basal areas. The brainstem, bilateral thalamic and hypothalamic areas, and ipsilateral caudate nucleus were also involved. Small areas of atrophy were detected in temporal lobes. The hippocampus and parahippocampal gyrus showed atrophy ipsilateral to the surgical approach. In the subgroup of endovascularly treated patients (n = 15), small areas of atrophy were detected in the bilateral orbitofrontal cortex and in the thalamic region. Twenty patients (54%) showed cognitive deficits in neuropsychological assessment. Group analysis after aSAH and treatment of the ruptured ACA aneurysm revealed gray matter atrophy, principally involving the frontobasal cortical areas and hippocampus ipsilateral to the surgical approach. Areas of reduced gray matter were more pronounced after surgical than endovascular treatment. Together with possible focal cortical infarctions and brain retraction deficits in individual patients, this finding may explain the neuropsychological disturbances commonly detected after treatment of ruptured ACA aneurysms. (orig.)

  8. Sensory Neurons Do Not Induce Motor Neuron Loss in a Human Stem Cell Model of Spinal Muscular Atrophy

    Science.gov (United States)

    Schwab, Andrew J.; Ebert, Allison D.

    2014-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system. PMID:25054590

  9. Simulating effects of brain atrophy in longitudinal PET imaging with an anthropomorphic brain phantom

    DEFF Research Database (Denmark)

    Jonasson, L S; Axelsson, J; Riklund, K

    2017-01-01

    cameras and reconstruction algorithms. Here, a 3D-printed anthropomorphic brain phantom with attachable striata in three sizes was designed to enable controlled volumetric changes. Using a method to eliminate the non-radioactive plastic wall, and manipulating BP levels by adding different number of events...

  10. 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.

  11. Effect of the cognitive rehabilitation in patients with mild cognitive impairment and identified brain atrophy

    Directory of Open Access Journals (Sweden)

    Petr Nilius

    2015-12-01

    Full Text Available Aim: The main objective of this study was to analyse the development of cognitive functions and effect of cognitive rehabilitation on patients diagnosed with mild cognitive impairment (MCI, as a result of brain atrophy. Design: A quantitative non-randomized intervention study on a control sample of patients. Methods: The effect was observed in a group of patients ranging 59-91 years of age (N = 36. Only patients fulfilling the diagnostic criteria of mild cognitive disorder diagnosed by tomography (CT that had undergone 22 sessions, were involved in the clinical sample (n = 21. The control sample (n = 15 consisted of patients without any neurological diagnosis and who did not undergo cognitive sessions. Results: The effect of cognitive rehabilitation was measured by Addenbrooke's cognitive test, revised in 2010 (ACE-R; affective changes were measured by Beck´s scale of depression BDI-2 and by a scale used to detect anxiety and depression: the Hospital Anxiety and Depression Scale (HADS. Subjective change and improvement were observed using the Clinical Global Impression (CGI psychiatric scale. Changes in the functional state of patients were measured by means of the activities of daily living scale (ADL, including the instrumental version (IADL. The effect was examined in the form of entry and output tests, which were verified by statistical analysis, a significant level being p > 0.05. Conclusions: Significant differences in verbal tests and ACE-R were observed in the clinical sample of patients. Some significant changes were observed in the field of affective symptoms, according to the HADS and BDI-2. The clinical sample showed a significant improvement in subjective clinical state (CGI. The ADL and IADL questionnaires seem to have been inadequate for purpose due to their low sensitivity. The effect of cognitive rehabilitation in patients diagnosed with mild cognitive disorder can be seen and verified in comparison with the control sample

  12. Multiple sclerosis patients lacking oligoclonal bands in the cerebrospinal fluid have less global and regional brain atrophy.

    Science.gov (United States)

    Ferreira, Daniel; Voevodskaya, Olga; Imrell, Kerstin; Stawiarz, Leszek; Spulber, Gabriela; Wahlund, Lars-Olof; Hillert, Jan; Westman, Eric; Karrenbauer, Virginija Danylaité

    2014-09-15

    To investigate whether multiple sclerosis (MS) patients with and without cerebrospinal fluid (CSF) oligoclonal immunoglobulin G bands (OCB) differ in brain atrophy. Twenty-eight OCB-negative and thirty-five OCB-positive patients were included. Larger volumes of total CSF and white matter (WM) lesions; smaller gray matter (GM) volume in the basal ganglia, diencephalon, cerebellum, and hippocampus; and smaller WM volume in corpus callosum, periventricular-deep WM, brainstem, and cerebellum, were observed in OCB-positives. OCB-negative patients, known to differ genetically from OCB-positives, are characterized by less global and regional brain atrophy. This finding supports the notion that OCB-negative MS patients may represent a clinically relevant MS subgroup. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Regional cerebral blood flow and brain atrophy in senile dementia of Alzheimer type (SDAT). Comparing with multi-infarct dementia (MID), and aged control

    Energy Technology Data Exchange (ETDEWEB)

    Okada, K.; Kobayashi, S.; Yamaguchi, S.; Kitani, M.; Tsunematsu, T.

    1987-05-01

    To investigate the relationship between the reduction of cerebal blood flow and brain atrophy in SDAT, these were measured in 13 cases of senile dementia of Alzheimer type, and compared to 15 cases of multi-infarct Dementia, 39 cases of lacunar infarction without dementia (non-demented CVD group) and 69 cases of aged normal control. Brain atrophy was evaluated by two-dimensional method on CT film by digitizer and regional cerebral blood flow (rCBF) was measured by /sup 133/Xe inhalation method. The degree of brain atrophy in SDAT was almost similar of that of MID. But it was more severe than that of non-demented group. MID showed the lowest rCBF among these groups. SDAT showed significantly lower rCBF than that of aged control, but rCBF in SDAT was equal to that of lacunar stroke without dementia. Focal reduction of cerebral blood flow in bilateral fronto-parietal and left occipital regions were observed in SDAT. Verbal intelligence score (Hasegawa's score) correlated with rCBF and brain atrophy index in MID, and a tendency of correlation between rCBF and brain atrophy in MID was also observed. However, there was no correlation among those indices in SDAT. These findings suggest that the loss of brain substance dose not correspond to the reduction of rCBF in SDAT and simultaneous measurement of rCBF and brain atrophy was useful to differ SDAT from MID.

  14. Electrical Guidance of Human Stem Cells in the Rat Brain

    Directory of Open Access Journals (Sweden)

    Jun-Feng Feng

    2017-07-01

    Full Text Available Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies.

  15. Traumatic Intracranial Hemorrhage Correlates with Preinjury Brain Atrophy, but Not with Antithrombotic Agent Use: A Retrospective Study

    OpenAIRE

    Dunham, C. Michael; Hoffman, David A.; Huang, Gregory S.; Omert, Laurel A.; Gemmel, David J.; Merrell, Renee

    2014-01-01

    Background 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. Materials and Methods 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...

  16. Quantitative magnetization transfer provides information complementary to grey matter atrophy in Alzheimer's disease brains.

    Science.gov (United States)

    Giulietti, Giovanni; Bozzali, Marco; Figura, Viviana; Spanò, Barbara; Perri, Roberta; Marra, Camillo; Lacidogna, Giordano; Giubilei, Franco; Caltagirone, Carlo; Cercignani, Mara

    2012-01-16

    Preliminary studies, based on a region-of-interest approach, suggest that quantitative magnetization transfer (qMT), an extension of magnetization transfer imaging, provides complementary information to conventional magnetic resonance imaging (MRI) in the characterisation of Alzheimer's disease (AD). The aim of this study was to extend these findings to the whole brain, using a voxel-wise approach. We recruited 19AD patients and 11 healthy subjects (HS). All subjects had an MRI acquisition at 3.0T including a T(1)-weighted volume, 12 MT-weighted volumes for qMT, and data for computing T(1) and B(1) maps. The T(1)-weighted volumes were processed to yield grey matter (GM) volumetric maps, while the other sequences were used to compute qMT parametric maps of the whole brain. qMT maps were warped to standard space and smoothed, and subsequently compared between groups. Of all the qMT parameters considered, only the forward exchange rate, RM(0)(B), showed significant group differences. These images were therefore retained for the multimodal statistical analysis, designed to locate brain regions of RM(0)(B) differences between AD and HS groups, adjusting for local GM atrophy. Widespread areas of reduced RM(0)(B) were found in AD patients, mainly located in the hippocampus, in the temporal lobe, in the posterior cingulate and in the parietal cortex. These results indicate that, among qMT parameters, RM(0)(B) is the most sensitive to AD pathology. This quantity is altered in the hippocampus of patients with AD (as found by previous works) but also in other brain areas, that PET studies have highlighted as involved with both, reduced glucose metabolism and amyloid β deposition. RM(0)(B) might reflect, through the measurement of the efficiency of MT exchange, some information with a specific pathological counterpart. Given previous evidence of a strict relationship between RM(0)(B) and intracellular pH, an intriguing speculation is that our findings might reflect metabolic

  17. Neither retinal nor brain atrophy can be shown in patients with isolated unilateral optic neuritis at the time of presentation

    DEFF Research Database (Denmark)

    Kallenbach, Klaus; Sander, Birgit; Tsakiri, Anna

    2011-01-01

    were calculated based on MRI. Additionally, visual evoked potentials (VEPs) were recorded. RESULTS: Neither OCT measurements nor brain volume measures revealed signs of localized or generalized atrophy in patients compared with healthy volunteers. Stratification of patients into high risk based...... on the presence of white matter lesions did not reveal differences. The association between OCT measures and brain volumes previously found could not be confirmed at the time of the first clinical event. VEP latency was significantly prolonged in patients with white matter lesions compared to those without...... lesions. A trend towards a relationship between VEP amplitude of fellow eyes and brain volumes was noted. CONCLUSIONS: In this cohort we were not able to show atrophic features in the retina or the brain, and the association between structural measures of the retina and the brain as indicated in the later...

  18. Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns.

    Science.gov (United States)

    Habes, M; Janowitz, D; Erus, G; Toledo, J B; Resnick, S M; Doshi, J; Van der Auwera, S; Wittfeld, K; Hegenscheid, K; Hosten, N; Biffar, R; Homuth, G; Völzke, H; Grabe, H J; Hoffmann, W; Davatzikos, C

    2016-04-05

    We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20-90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (Prisk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD.

  19. Muscle atrophy

    Science.gov (United States)

    Muscle wasting; Wasting; Atrophy of the muscles ... There are two types of muscle atrophy: disuse and neurogenic. Disuse atrophy is caused by not using the muscles enough . This type of atrophy can often be ...

  20. Simulating effects of brain atrophy in longitudinal PET imaging with an anthropomorphic brain phantom

    Science.gov (United States)

    Jonasson, L. S.; Axelsson, J.; Riklund, K.; Boraxbekk, C. J.

    2017-07-01

    In longitudinal positron emission tomography (PET), the presence of volumetric changes over time can lead to an overestimation or underestimation of the true changes in the quantified PET signal due to the partial volume effect (PVE) introduced by the limited spatial resolution of existing PET cameras and reconstruction algorithms. Here, a 3D-printed anthropomorphic brain phantom with attachable striata in three sizes was designed to enable controlled volumetric changes. Using a method to eliminate the non-radioactive plastic wall, and manipulating BP levels by adding different number of events from list-mode acquisitions, we investigated the artificial volume dependence of BP due to PVE, and potential bias arising from varying BP. Comparing multiple reconstruction algorithms we found that a high-resolution ordered-subsets maximization algorithm with spatially variant point-spread function resolution modeling provided the most accurate data. For striatum, the BP changed by 0.08% for every 1% volume change, but for smaller volumes such as the posterior caudate the artificial change in BP was as high as 0.7% per 1% volume change. A simple gross correction for striatal volume is unsatisfactory, as the amplitude of the PVE on the BP differs depending on where in the striatum the change occurred. Therefore, to correctly interpret age-related longitudinal changes in the BP, we must account for volumetric changes also within a structure, rather than across the whole volume. The present 3D-printing technology, combined with the wall removal method, can be implemented to gain knowledge about the predictable bias introduced by the PVE differences in uptake regions of varying shape.

  1. 3D characterization of brain atrophy in Alzheimer's disease and mild cognitive impairment using tensor-based morphometry.

    Science.gov (United States)

    Hua, Xue; Leow, Alex D; Lee, Suh; Klunder, Andrea D; Toga, Arthur W; Lepore, Natasha; Chou, Yi-Yu; Brun, Caroline; Chiang, Ming-Chang; Barysheva, Marina; Jack, Clifford R; Bernstein, Matt A; Britson, Paula J; Ward, Chadwick P; Whitwell, Jennifer L; Borowski, Bret; Fleisher, Adam S; Fox, Nick C; Boyes, Richard G; Barnes, Josephine; Harvey, Danielle; Kornak, John; Schuff, Norbert; Boreta, Lauren; Alexander, Gene E; Weiner, Michael W; Thompson, Paul M

    2008-05-15

    Tensor-based morphometry (TBM) creates three-dimensional maps of disease-related differences in brain structure, based on nonlinearly registering brain MRI scans to a common image template. Using two different TBM designs (averaging individual differences versus aligning group average templates), we compared the anatomical distribution of brain atrophy in 40 patients with Alzheimer's disease (AD), 40 healthy elderly controls, and 40 individuals with amnestic mild cognitive impairment (aMCI), a condition conferring increased risk for AD. We created an unbiased geometrical average image template for each of the three groups, which were matched for sex and age (mean age: 76.1 years+/-7.7 SD). We warped each individual brain image (N=120) to the control group average template to create Jacobian maps, which show the local expansion or compression factor at each point in the image, reflecting individual volumetric differences. Statistical maps of group differences revealed widespread medial temporal and limbic atrophy in AD, with a lesser, more restricted distribution in MCI. Atrophy and CSF space expansion both correlated strongly with Mini-Mental State Exam (MMSE) scores and Clinical Dementia Rating (CDR). Using cumulative p-value plots, we investigated how detection sensitivity was influenced by the sample size, the choice of search region (whole brain, temporal lobe, hippocampus), the initial linear registration method (9- versus 12-parameter), and the type of TBM design. In the future, TBM may help to (1) identify factors that resist or accelerate the disease process, and (2) measure disease burden in treatment trials.

  2. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Facchino, Sabrina; Abdouh, Mohamed [Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l' Assomption, Montreal, H1T 2M4 (Canada); Bernier, Gilbert, E-mail: gbernier.hmr@ssss.gouv.qc.ca [Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l' Assomption, Montreal, H1T 2M4 (Canada); Faculté de Médecine, Université de Montréal, Montréal, H3T 1J4 (Canada)

    2011-03-30

    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM “cancer stem cells” were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings.

  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. 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

  5. Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury.

    Science.gov (United States)

    Ruitenberg, Marc J; Blits, Bas; Dijkhuizen, Paul A; te Beek, Erik T; Bakker, Arne; van Heerikhuize, Joop J; Pool, Chris W; Hermens, Wim T J; Boer, Gerard J; Verhaagen, Joost

    2004-03-01

    Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesion-induced atrophy by adeno-associated viral (AAV) vector-mediated gene transfer of brain-derived neurotrophic factor (BDNF). We show for the first time that AAV vectors can be used for the persistent transduction of highly atrophic neurons in the red nucleus (RN) for up to 18 months after injury. Furthermore, BDNF gene transfer into the RN following spinal axotomy resulted in counteraction of atrophy in both the acute and chronic stage after injury. These novel findings demonstrate that a gene therapeutic approach can be used to reverse atrophy of lesioned CNS neurons for an extended period of time.

  6. 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. PMID:27003218

  7. 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

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

    Science.gov (United States)

    Dunham, C Michael; Hoffman, David A; Huang, Gregory S; Omert, Laurel A; Gemmel, David J; Merrell, Renee

    2014-01-01

    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

  9. Neonatal bilateral diaphragmatic paralysis caused by brain stem haemorrhage.

    OpenAIRE

    Blazer, S; Hemli, J A; Sujov, P O; Braun, J.

    1989-01-01

    We describe a neonate with severe bilateral diaphragmatic paralysis caused by haemorrhage in the lower brain stem. To our knowledge this association has not been previously reported in the English medical literature.

  10. Neurosyphilis Involving Cranial Nerves in Brain Stem: 2 Case Reports

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Ji Hye [Dept. of Radiology, Kyung Hee University College of Medicine, Seoul (Korea, Republic of); Choi, Woo Suk; Kim, Eui Jong [Dept. of Radiology, Kyung Hee University Hospital, Seoul (Korea, Republic of); Yoon, Sung Sang; Heo, Sung Hyuk [Dept. of Neurology, Kyung Hee University Hospital, Seoul (Korea, Republic of)

    2012-01-15

    Neurosyphilis uncommonly presents with cranial neuropathies in acute syphilitic meningitis and meningovascular neurosyphilis. We now report two cases in which the meningeal form of neurosyphilis involved cranial nerves in the brain stem: the oculomotor and trigeminal nerve.

  11. Patterns of brain atrophy associated with episodic memory and semantic fluency decline in aging.

    Science.gov (United States)

    Pelletier, Amandine; Bernard, Charlotte; Dilharreguy, Bixente; Helmer, Catherine; Le Goff, Melanie; Chanraud, Sandra; Dartigues, Jean-François; Allard, Michèle; Amieva, Hélène; Catheline, Gwénaëlle

    2017-03-09

    The cerebral substratum of age-related cognitive decline was evaluated in an elderly-cohort followed for 12 years (n=306). Participants, free of dementia, received neuropsychological assessments every two years and an MRI exam at baseline and four years later. Cognitive decline was evaluated on two broadly used tests to detect dementia: the Free and Cued Selective Reminding Test (FCSRT), a verbal episodic memory task, and the Isaacs Set Test (IST), a semantic fluency task. Using voxel-based approach, the relationship between cognitive decline with 1/ baseline grey matter volumes and 2/ grey matter volume loss between the two scans was explored. Baseline volumes analysis revealed that FCSRT and IST declines were both associated with lower volumes of the medial temporal region. Volumes loss analysis confirmed that both declines are related to medial temporal lobe atrophy and revealed that FCSRT decline was specifically associated with atrophy of the posterior cingulate cortex whereas IST decline was specifically related to temporal pole atrophy. These results suggest that cognitive decline across aging is firstly related to structural modifications of the medial temporal lobe, followed by an atrophy in the posterior midline structures for episodic memory and an atrophy of the temporal pole for semantic fluency.

  12. Global and regional brain atrophy is associated with low or retrograde facial vein flow in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Dejan Jakimovski

    2017-09-01

    Full Text Available Increased collateral facial vein (FV flow may be associated with structural damage in patients with multiple sclerosis (MS. The objective was to assess differences in FV flow and magnetic resonance imaging (MRI-derived outcomes in MS. The study included 136 MS patients who underwent neck and head vascular system examination by echo-color Doppler. Inflammatory MRI markers were assessed on a 3T MRI using a semi-automated edge detection and contouring/ thresholding technique. MRI volumetric outcomes of whole brain (WB, gray matter (GM, white matter (WM, cortex, ventricular cerebrospinal fluid (vCSF, deep gray matter (DGM, thalamus, caudate nucleus (CN, putamen, globus pallidus (GP, and hippocampus were calculated. Independent t-test and ANCOVA, adjusted for age, were used to compare groups based on FV flow quartiles. Thirty-four MS patients with FV flow ≤327.8 mL/min (lowest quartile had significantly lower WB (P327.8 mL/min (higher quartiles. There were no differences in T1-, T2- and gadolinium- enhancing lesion volumes between the quartile groups. The lack of an association between FV blood flow and inflammatory MRI measures in MS patients, but an association with brain atrophy, suggests that the severity of neurodegenerative process may be related to hemodynamic alterations. MS patients with more advanced global and regional brain atrophy showed low or retrograde FV volume flow.

  13. Distributed abnormalities of brain white matter architecture in patients with dominant optic atrophy and OPA1 mutations.

    Science.gov (United States)

    Rocca, Maria A; Bianchi-Marzoli, Stefania; Messina, Roberta; Cascavilla, Maria Lucia; Zeviani, Massimo; Lamperti, Costanza; Milesi, Jacopo; Carta, Arturo; Cammarata, Gabriella; Leocani, Letizia; Lamantea, Eleonora; Bandello, Francesco; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

    2015-05-01

    Using advanced MRI techniques, we investigated the presence and topographical distribution of brain grey matter (GM) and white matter (WM) alterations in dominant optic atrophy (DOA) patients with genetically proven OPA1 mutation as well as their correlation with clinical and neuro-ophthalmologic findings. Nineteen DOA patients underwent neurological, neuro-ophthalmologic and brainstem auditory evoked potentials (BAEP) evaluations. Voxel-wise methods were applied to assess regional GM and WM abnormalities in patients compared to 20 healthy controls. Visual acuity was reduced in 16 patients. Six DOA patients (4 with missense mutations) had an abnormal I peripheral component (auditory nerve) at BAEP. Compared to controls, DOA patients had significant atrophy of the optic nerves (p < 0.0001). Voxel-based morphometry (VBM) analysis showed that, compared to controls, DOA patients had significant WM atrophy of the chiasm and optic tracts; whereas no areas of GM atrophy were found. Tract-based spatial statistics (TBSS) analysis showed that compared to controls, DOA patients had significantly lower mean diffusivity, axial and radial diffusivity in the WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. No correlations were found between volumetric and diffusivity abnormalities quantified with MRI and clinical and neuro-ophthalmologic measures of disease severity. Consistently with pathological studies, tissue loss in DOA patients is limited to anterior optic pathways reflecting retinal ganglion cell degeneration. Distributed abnormalities of diffusivity indexes might reflect abnormal intracellular mitochondrial morphology as well as alteration of protein levels due to OPA1 mutations.

  14. Brain stem hypoplasia associated with Cri-du-Chat syndrome.

    Science.gov (United States)

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

    2013-01-01

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

  15. Brain stem hypoplasia associated with Cri-du-Chat syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu [Dept. of Radiology, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of)

    2013-12-15

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

  16. Brain Stem Hypoplasia Associated with Cri-du-Chat Syndrome

    OpenAIRE

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

    2013-01-01

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for th...

  17. Regional brain atrophy and functional connectivity changes related to fatigue in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Álvaro Javier Cruz Gómez

    Full Text Available Fatigue is one of the most frequent symptoms in multiple sclerosis (MS, and recent studies have described a relationship between the sensorimotor cortex and its afferent and efferent pathways as a substrate of fatigue. The objectives of this study were to assess the neural correlates of fatigue in MS through gray matter (GM and white matter (WM atrophy, and resting state functional connectivity (rs-FC of the sensorimotor network (SMN. Eighteen healthy controls (HCs and 60 relapsing-remitting patients were assessed with the Fatigue Severity Scale (FSS. Patients were classified as fatigued (F or nonfatigued (NF. We investigated GM and WM atrophy using voxel-based morphometry, and rs-FC changes with a seed-based method and independent component analysis (ICA. F patients showed extended GM and WM atrophy focused on areas related to the SMN. High FSS scores were associated with reductions of WM in the supplementary motor area. Seed analysis of GM atrophy in the SMN showed that HCs presented increased rs-FC between the primary motor and somatosensory cortices while patients with high FSS scores were associated with decreased rs-FC between the supplementary motor area and associative somatosensory cortex. ICA results showed that NF patients presented higher rs-FC in the primary motor cortex compared to HCs and in the premotor cortex compared to F patients. Atrophy reduced functional connectivity in SMN pathways and MS patients consequently experienced high levels of fatigue. On the contrary, NF patients experienced high synchronization in this network that could be interpreted as a compensatory mechanism to reduce fatigue sensation.

  18. Derivation of human embryonic stem cell from spinal muscular atrophy patient

    Directory of Open Access Journals (Sweden)

    Pingyuan Xie

    2016-03-01

    Full Text Available We established a human embryonic stem cell (hESC line chHES-427 from the abnormal embryo carrying homozygous deletion of exon 7 of survival motor neuron gene (SMN. This cell line maintained a normal karyotype 46, XX during long-term culture. Further characteristic analysis suggested that the cells expressed the pluripotency-related markers and had the capacity to differentiate into the derivatives from the three germ layers in vitro.

  19. Rates of brain atrophy and clinical decline over 6 and 12-month intervals in PSP: determining sample size for treatment trials.

    Science.gov (United States)

    Whitwell, Jennifer L; Xu, Jia; Mandrekar, Jay N; Gunter, Jeffrey L; Jack, Clifford R; Josephs, Keith A

    2012-03-01

    Imaging biomarkers are useful outcome measures in treatment trials. We compared sample size estimates for future treatment trials performed over 6 or 12-months in progressive supranuclear palsy using both imaging and clinical measures. We recruited 16 probable progressive supranuclear palsy patients that underwent baseline, 6 and 12-month brain scans, and 16 age-matched controls with serial scans. Disease severity was measured at each time-point using the progressive supranuclear palsy rating scale. Rates of ventricular expansion and rates of atrophy of the whole brain, superior frontal lobe, thalamus, caudate and midbrain were calculated. Rates of atrophy and clinical decline were used to calculate sample sizes required to power placebo-controlled treatment trials over 6 and 12-months. Rates of whole brain, thalamus and midbrain atrophy, and ventricular expansion, were increased over 6 and 12-months in progressive supranuclear palsy compared to controls. The progressive supranuclear palsy rating scale increased by 9 points over 6-months, and 18 points over 12-months. The smallest sample size estimates for treatment trials over 6-months were achieved using rate of midbrain atrophy, followed by rate of whole brain atrophy and ventricular expansion. Sample size estimates were further reduced over 12-month intervals. Sample size estimates for the progressive supranuclear palsy rating scale were worse than imaging measures over 6-months, but comparable over 12-months. Atrophy and clinical decline can be detected over 6-months in progressive supranuclear palsy. Sample size estimates suggest that treatment trials could be performed over this interval, with rate of midbrain atrophy providing the best outcome measure. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. The presence of family during brain stem death testing.

    Science.gov (United States)

    Doran, Majella

    2004-02-01

    Prior to 1959, cardiac and respiratory cessation was universally and unambiguously accepted as confirming the death of a person [M. Morioka, J. Clin. Nurs. 10 (2001) 132; Reconsidering brain death: a lesson from Japan's fifteen years of experience, 2001, http://proquest.umi.com/pqdweb]. However, with the rapid pace of modern technology and resuscitation techniques, the boundaries between life and death have become blurred [J. Bothamley, Organ donation: brain stem death, 2000, http://proquest.umi.com/pqdweb; Re-examining death: against a higher brain criterion, 1999, http://proquest.umi.com/pqdweb]. As a result, a redefinition of death, "brain death" has emerged [M. Brazier, Medicine, Patients and the Law, New ed., Penquin Books, London, 1992]. Most families faced with the brain stem death of a relative find the concept difficult to understand and have trouble in accepting that their relative is actually dead. In Part One of this two part series, the needs of families who are facing the brain stem death of a family member will be examined and explanations offered as to why families find the concept difficult to grasp. In addition, it will also advocate that family members are given the choice to be or not to be present during brain stem death testing. It is suggested that the presence of family members during brain stem death testing not only helps families to accept this concept of death but also promotes the grieving process. In Part Two, the barriers that inhibit family involvement and presence will be explored and methods for involving family proposed.

  1. Effects of baseline CSF α-synuclein on regional brain atrophy rates in healthy elders, mild cognitive impairment and Alzheimer's disease.

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    Niklas Mattsson

    Full Text Available BACKGROUND: Cerebrospinal fluid (CSF α-synuclein is reduced in synucleinopathies, including dementia with Lewy bodies, and some studies have found increased CSF α-synuclein in Alzheimer's disease (AD. No study has explored effects of CSF α-synuclein on brain atrophy. Here we tested if baseline CSF α-synuclein affects brain atrophy rates and if these effects vary across brain regions, and across the cognitive spectrum from healthy elders (NL, to patients with mild cognitive impairment (MCI and AD. METHODS: Baseline CSF α-synuclein measurements and longitudinal structural brain magnetic resonance imaging was performed in 74 NL, 118 MCI patients and 55 AD patients. Effects of baseline CSF α-synuclein on regional atrophy rates were tested in 1 four pre-hoc defined regions possibly associated with Lewy body and/or AD pathology (amygdala, caudate, hippocampus, brainstem, and 2 all available regions of interest. Differences across diagnoses were tested by assessing the interaction of CSF α-synuclein and diagnosis (testing NL versus MCI, and NL versus AD. RESULTS: The effects of CSF α-synuclein on longitudinal atrophy rates were not significant after correction for multiple comparisons. There were tendencies for effects in AD in caudate (higher atrophy rates in subjects with higher CSF α-synuclein, P=0.046 and brainstem (higher atrophy rates in subjects with lower CSF α-synuclein, P=0.063. CSF α-synuclein had significantly different effects on atrophy rates in NL and AD in brainstem (P=0.037 and caudate (P=0.006. DISCUSSION: With the possible exception of caudate and brainstem, the overall weak effects of CSF α-synuclein on atrophy rates in NL, MCI and AD argues against CSF α-synuclein as a biomarker related to longitudinal brain atrophy in these diagnostic groups. Any effects of CSF α-synuclein may be attenuated by possible simultaneous occurrence of AD-related neuronal injury and concomitant Lewy body pathology, which may elevate and

  2. Brain atrophy and lesion load are related to CSF lipid-specific IgM oligoclonal bands in clinically isolated syndromes

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    Magraner, Maria Jose; Bosca, Isabel; Simo-Castello, Maria; Casanova, Bonaventura [Hospital La Fe, Multiple Sclerosis Unit, Neurology Department, Valencia (Spain); Garcia-Marti, Gracian [Hospital Quiron, Magnetic Resonance Unit, Valencia (Spain); CIBER Mental Health Network, ISCIII, Valencia (Spain); Alberich-Bayarri, Angel; Marti-Bonmati, Luis [Hospital Quiron, Magnetic Resonance Unit, Valencia (Spain); Coret, Francisco [Hospital Clinic Universitari, Multiple Sclerosis Unit, Neurology Department, Valencia (Spain); Alvarez-Cermeno, Jose C. [Hospital Ramon y Cajal, Neurology Department, Madrid (Spain); Villar, Luisa M. [Hospital Ramon y Cajal, Immunology Department, Madrid (Spain)

    2012-01-15

    The objective of this work is to study the relationship between the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in CSF, with both T2 lesion volume (T2LV) accumulation and brain atrophy (percentage change of brain volume-PCBV-and brain parenchyma fraction-BPF) in patients with clinically isolated syndromes (CIS) suggestive of demyelination. Twenty-four CIS patients were included in this prospective study. IgG oligoclonal bands (OCGB) and LS-OCMB were determined in paired serum and CSF samples within 3 months since clinical onset. Brain MRI studies were scheduled at baseline, 3 months, first and second years after CIS onset. Differences in T2LV, PCBV and BPF between CIS patients according to the type of OCB were studied. Nine patients had no OCB; 15 had only OCGB, and seven had OCGB + LS-OCMB present in the CSF. LS-OCMB were associated with greater T2LV in all scheduled MRI studies. At the end of follow-up (year 2), it was threefold higher in patients with these antibodies than in those without LS-OCMB (3.95 cm{sup 3} vs. 1.36 cm{sup 3}, p = 0.001). At that point, brain atrophy was also higher in patients with LS-OCMB (BPF, 0.73 in LS-OCMB+ patients vs. 0.76 in negative ones, p = 0.03). The rate in brain atrophy was higher in the first group of patients as well. Considering only patients with OCGB, the presence of LS-OCMB was also related to greater T2LV, T2LV increase and a trend towards higher atrophy rate. The presence of LS-OCMB in the first event suggestive of demyelination is related to an early increase in lesion load and brain atrophy. These data are in line with prospective studies showing the clinical prognostic value of LS-OCMB. (orig.)

  3. Optic atrophy 1 mediates coenzyme Q-responsive regulation of respiratory complex IV activity in brain mitochondria.

    Science.gov (United States)

    Takahashi, Kazuhide; Ohsawa, Ikuroh; Shirasawa, Takuji; Takahashi, Mayumi

    2017-11-01

    The oxygen consumption rate (OCR) in brain mitochondria is significantly lower in aged mice than in young mice, and the reduced OCR is rescued by administration of water-solubilized CoQ10 to aged mice via drinking water. However, the mechanism behind this remains unclear. Here, we show that the activity of respiratory complex IV (CIV) in brain mitochondria declined in aged mice than in young mice, with no significant change in individual respiratory complex levels and their supercomplex assembly. Reduced CIV activity in the aged mice coincided with reduced binding of optic atrophy 1 (OPA1) to CIV. Both reduced activity and OPA1 binding of CIV were rescued by water-solubilized CoQ10 administration to aged mice via drinking water. OCR and the activity and OPA1 binding of CIV in isolated brain mitochondria from aged mice were restored by incubation with CoQ10, but not in the presence of 15-deoxy-prostaglandin J2, an inhibitor of a GTPase effector domain-containing GTPase such as OPA1 and DRP1. By contrast, the CoQ10-responsive restoration of OCR in the isolated mitochondria was not inhibited by Mdivi-1, a selective inhibitor of DRP1. Thus, we propose a novel function of OPA1 in regulating the CIV activity in brain mitochondria in response to CoQ10. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Mapping the calcitonin receptor in human brain stem

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    Bower, Rebekah L; Eftekhari, Sajedeh; Waldvogel, Henry J

    2016-01-01

    understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract...... receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our...

  5. Brain stem auditory evoked responses in human infants and adults

    Science.gov (United States)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  6. Human Brain Stem Structures Respond Differentially to Noxious Heat

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    Alexander eRitter

    2013-09-01

    Full Text Available Concerning the physiological correlates of pain, the brain stem is considered to be one core region that is activated by noxious input. In animal studies, different slopes of skin heating (SSH with noxious heat led to activation in different columns of the midbrain periaqueductal grey (PAG. The present study aimed at finding a method for differentiating structures in PAG and other brain stem structures, which are associated with different qualities of pain in humans according to the structures that were associated with different behavioral significances to noxious thermal stimulation in animals. Brain activity was studied by fMRI in healthy subjects in response to steep and shallow SSH with noxious heat. We found differential activation to different SSH in the PAG and the rostral ventromedial medulla (RVM. In a second experiment we demonstrate that the different SSH were associated with different pain qualities. Our experiments provide evidence that brainstem structures, i.e. the PAG and the RVM, become differentially activated by different SSH. Therefore, different SSH can be utilized when brain stem structures are investigated and when it is aimed to activate these structures differentially. Moreover, percepts of first pain were elicited by shallow SSH whereas percepts of second pain were elicited by steep SSH. The stronger activation of these brain stem structures to SSH, eliciting percepts of second vs. first pain, might be of relevance for activating different coping strategies in response to the noxious input with the two types of SSH.

  7. Altered α-synuclein, parkin, and synphilin isoform levels in multiple system atrophy brains

    DEFF Research Database (Denmark)

    Brudek, Tomasz; Winge, Kristian; Rasmussen, Nadja Bredo

    2016-01-01

    Together with Parkinson's disease (PD) and dementia with Lewy bodies, multiple system atrophy (MSA) is a member of a diverse group of neurodegenerative disorders termed α-synucleinopathies. Previously, it has been shown that α-synuclein, parkin, and synphilin-1 display disease......-specific transcription patterns in frontal cortex in PD, dementia with Lewy bodies, and MSA, and thus may mediate the development of α-synucleinopathies. In this study, the differential expression of α-synuclein isoforms on transcriptional and translational levels was ascertained in MSA patients in comparison with PD...

  8. Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis [version 2; referees: 1 approved, 2 approved with reservations

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    Alex Lewin

    2016-12-01

    Full Text Available Background A major cause of disability in secondary progressive multiple sclerosis (SPMS is progressive brain atrophy, whose pathogenesis is not fully understood. The objective of this study was to identify protein biomarkers of brain atrophy in SPMS.   Methods We used surface-enhanced laser desorption-ionization time-of-flight mass spectrometry to carry out an unbiased search for serum proteins whose concentration correlated with the rate of brain atrophy, measured by serial MRI scans over a 2-year period in a well-characterized cohort of 140 patients with SPMS.  Protein species were identified by liquid chromatography-electrospray ionization tandem mass spectrometry.   Results There was a significant (p<0.004 correlation between the rate of brain atrophy and a rise in the concentration of proteins at 15.1 kDa and 15.9 kDa in the serum.  Tandem mass spectrometry identified these proteins as alpha-haemoglobin and beta-haemoglobin, respectively.  The abnormal concentration of free serum haemoglobin was confirmed by ELISA (p<0.001.  The serum lactate dehydrogenase activity was also highly significantly raised (p<10-12 in patients with secondary progressive multiple sclerosis.    Conclusions The results are consistent with the following hypothesis. In progressive multiple sclerosis, low-grade chronic intravascular haemolysis releases haemoglobin into the serum; the haemoglobin is subsequently translocated into the central nervous system (CNS across the damaged blood-brain barrier.  In the CNS, the haemoglobin and its breakdown products, including haem and iron, contribute to the neurodegeneration and consequent brain atrophy seen in progressive disease. We postulate that haemoglobin is a source of the iron whose deposition along blood vessels in multiple sclerosis plaques is associated with neurodegeneration.  If so, then chelators of haemoglobin, rather than chelators of free serum iron, may be effective in preventing this

  9. Human adipose-derived mesenchymal stem cells as a new model of spinal and bulbar muscular atrophy.

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    Marta Dossena

    Full Text Available Spinal and bulbar muscular atrophy (SBMA or Kennedy's disease is an X-linked CAG/polyglutamine expansion motoneuron disease, in which an elongated polyglutamine tract (polyQ in the N-terminal androgen receptor (ARpolyQ confers toxicity to this protein. Typical markers of SBMA disease are ARpolyQ intranuclear inclusions. These are generated after the ARpolyQ binds to its endogenous ligands, which promotes AR release from chaperones, activation and nuclear translocation, but also cell toxicity. The SBMA mouse models developed so far, and used in preclinical studies, all contain an expanded CAG repeat significantly longer than that of SBMA patients. Here, we propose the use of SBMA patients adipose-derived mesenchymal stem cells (MSCs as a new human in vitro model to study ARpolyQ toxicity. These cells have the advantage to express only ARpolyQ, and not the wild type AR allele. Therefore, we isolated and characterized adipose-derived MSCs from three SBMA patients (ADSC from Kennedy's patients, ADSCK and three control volunteers (ADSCs. We found that both ADSCs and ADSCKs express mesenchymal antigens, even if only ADSCs can differentiate into the three typical cell lineages (adipocytes, chondrocytes and osteocytes, whereas ADSCKs, from SBMA patients, showed a lower growth potential and differentiated only into adipocyte. Moreover, analysing AR expression on our mesenchymal cultures we found lower levels in all ADSCKs than ADSCs, possibly related to negative pressures exerted by toxic ARpolyQ in ADSCKs. In addition, with proteasome inhibition the ARpolyQ levels increased specifically in ADSCKs, inducing the formation of HSP70 and ubiquitin positive nuclear ARpolyQ inclusions. Considering all of this evidence, SBMA patients adipose-derived MSCs cultures should be considered an innovative in vitro human model to understand the molecular mechanisms of ARpolyQ toxicity and to test novel therapeutic approaches in SBMA.

  10. [State dependent modification of auditory brain stem potentials].

    Science.gov (United States)

    Maier, R; Rebentisch, E

    1984-11-01

    It is well known, amplitudes and latencies of auditory brain stem potentials are almost independent of viligance state. Contrary to that, simple cognitive requirements effect amplitude changes (enhancement of variance, amplitude reduction) in a part 2/3) of the subjects.

  11. Diabetes increases atrophy and vascular lesions on brain MRI in patients with symptomatic arterial disease

    NARCIS (Netherlands)

    Tiehuis, Audrey M.; Van der Graaf, Yolanda; Visseren, Frank L.; Vincken, Koen L.; Biessels, Geert Jan; Appelman, Auke P. A.; Kappelle, L. Jaap; Mali, Willem P. T. M.

    Background and Purpose - Diabetes type 2 (DM2) is associated with accelerated cognitive decline and structural brain abnormalities. Macrovascular disease has been described as a determinant for brain MRI changes in DM2, but little is known about the involvement of other DM2-related factors. Methods

  12. Changes in the Cell Population in Brain White Matter in Multiple System Atrophy

    DEFF Research Database (Denmark)

    Nykjaer, Charlotte Havelund; Brudek, Tomasz; Salvesen, Lisette

    2017-01-01

    . OBJECTIVES AND METHODS: To establish the extent of involvement of the white matter in the disease, we have used stereology to quantify the total number of neurons and glial cells (oligodendrocytes, astrocytes, and microglia) in the brains from 10 MSA patients and 11 controls. RESULTS: The mean total number...... of white matter interstitial neurons in the patient brains was 0.5 × 10(9) (coefficient of variation = standard deviation/mean = 0.37), which was significantly lower than the 1.1 × 10(9) (0.41) in the control brains (P = .001) and equal to a reduction by ∼50%. The patient brains had a significantly higher...... found widespread microgliosis without concomitant astrogliosis in brain white matter in MSA patients and demonstrated an absence of significant oligodendrocyte degeneration. The exact role of oligodendrocytes in MSA pathogenesis, including neurodegeneration, remains to be elucidated. © 2017...

  13. Oligoclonal bands in the cerebrospinal fluid and increased brain atrophy in early stages of relapsing-remitting multiple sclerosis

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    Juan Ignacio Rojas

    2012-08-01

    Full Text Available OBJECTIVE: To determine if the presence of oligoclonal bands (OB at early stages of multiple sclerosis was associated with higher brain atrophy, when compared with patients without OB. METHODS: Relapsing-remitting multiple sclerosis (RRMS patients with less than two years of disease onset and OB detection in cerebrospinal fluid (CSF were included. SIENAX was used for total brain volume (TBV, gray matter volume (GMV, and white matter volume (WMV. RESULTS: Forty patients were included, 29 had positive IgG-OB. No differences were found between positive and negative patients in gender, expanded disability status scale (EDSS, treatment received, and T2/T1 lesion load. TBV in positive IgG-OB patients was 1.5 mm³ x 10(6 compared with 1.64 mm³ x 10(6 in the negative ones (p=0.02. GMV was 0.51 mm³ x 10(6 in positive IgG-OB compared with 0.62 mm³ x 10(6 in negative ones (p=0.002. No differences in WMV (p=0.09 were seen. CONCLUSIONS: IgG-OB in the CSF was related to neurodegeneration magnetic resonance (MR markers in early RRMS.

  14. Pathological and immunohistochemical study of lethal primary brain stem injuries

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    Rongchao Sun

    2012-05-01

    Full Text Available Abstract Background Many of the deaths that occur shortly after injury or in hospitals are caused by mild trauma. Slight morphological changes are often found in the brain stems of these patients during autopsy. The purpose of this study is to investigate the histopathological changes involved in primary brain stem injuries (PBSI and their diagnostic significance. Methods A total of 65 patients who had died of PBSI and other conditions were randomly selected. They were divided into 2 groups, an injury group (25 cases and a control group (20 cases. Slides of each patient’s midbrain, pons, and medulla oblongata were prepared and stained with HE, argentaffin, and immunohistochemical agents (GFAP, NF, amyloid-ß, MBP. Under low power (×100 and NF staining, the diameter of the thickest longitudinal axon was measured at its widest point. Ten such diameters were collected for each part of the brain (midbrain, pons, and medulla oblongata. Data were recorded and analyzed statistically. Results Brain stem contusions, astrocyte activity, edema, and pathological changes in the neurons were visibly different in the injury and control groups (P P  Conclusions These histopathological changes may prove beneficial to the pathological diagnosis of PBSI during autopsy. The measurement of axon diameters provides a referent quantitative index for the diagnosis of the specific causes of death involved in PBSI. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1345298818712204

  15. Stem Cell Technology for (Epi)genetic Brain Disorders.

    Science.gov (United States)

    Riemens, Renzo J M; Soares, Edilene S; Esteller, Manel; Delgado-Morales, Raul

    2017-01-01

    Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems. This, together with our incomplete knowledge of the multifactorial causes in the majority of these disorders, as well as a thorough understanding of associated (epi)genetic alterations, has been impeding progress in gaining more mechanistic insights from translational studies. Over the last years, however, stem cell technology has been offering an alternative approach to study and treat human brain disorders. Owing to this technology, we are now able to obtain a theoretically inexhaustible source of human neural cells and precursors in vitro that offer a platform for disease modeling and the establishment of therapeutic interventions. In addition to the potential to increase our general understanding of how (epi)genetic alterations contribute to the pathology of brain disorders, stem cells and derivatives allow for high-throughput drugs and toxicity testing, and provide a cell source for transplant therapies in regenerative medicine. In the current chapter, we will demonstrate the validity of human stem cell-based models and address the utility of other stem cell-based applications for several human brain disorders with multifactorial and (epi)genetic bases, including Parkinson's disease (PD), Alzheimer's disease (AD), fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Rett syndrome (RTT).

  16. Autologous adipose-derived stem cells attenuate muscular atrophy and protect spinal cord ventral horn motor neurons in an animal model of burn injury.

    Science.gov (United States)

    Wu, Sheng-Hua; Huang, Shu-Hung; Lo, Yi-Ching; Chai, Chee-Yin; Lee, Su-Shin; Chang, Kao-Ping; Lin, Sin-Daw; Lai, Chung-Sheng; Yeh, Jwu-Lai; Kwan, Aij-Lie

    2015-08-01

    Burn injuries might increase muscle mass loss, but the mechanisms are still unclear. In this study, we demonstrated that burn injury induced spinal cord ventral horn motor neuron (VHMN) apoptosis and subsequently caused muscle atrophy and revealed the potential protection of autologous adipose-derived stem cells (ASCs) transplantation on spinal cord VHMNs and muscle against burn injury. Third-degree hind-paw burns were established by contact with a 75°C metal surface for 10 seconds. Adipose tissues were harvested from the groin fat pad, expanded in culture and labeled with chloromethyl-benzamido/1,1'-dioctadecyl-3,3,3',3'- tetramethyl indocarbocyanine perchlorate. The ASCs were transplanted into the injured hind paw at 4 weeks after burn injury. The lumbar spinal cord, sciatic nerve, gastrocnemius muscle and hind-paw skin were processed for immunofluorescent staining at 4 weeks after transplantation, including terminal deoxynucleotidyl transferase (TUNEL) assay, caspase-3, caspase-9, CD 90 and S100, and the gastrocnemius muscle was evaluated through the use of hematoxylin and eosin staining. Caspase-3-positive, caspase-9-positive and TUNEL-positive cells were significantly increased in the corresponding dermatome spinal cord VHMNs after burn injury. Moreover, the decrease of Schwann cells in sciatic nerve and the increase of denervation atrophy in gastrocnemius muscle were observed. Furthermore, ASCs transplantation significantly attenuated apoptotic death of VHMNs and the area of muscle denervation atrophy in the gastrocnemius muscle fibers. The animal model of third-degree burns in the hind paw showed significant apoptosis in the corresponding spinal cord VHMNs, which suggests that neuroprotection might be the potentially therapeutic target in burn-induced muscle atrophy. ASCs have potential neuroprotection against burn injuries through its anti-apoptotic effects. Copyright © 2015. Published by Elsevier Inc.

  17. The effect of disease modifying therapies on brain atrophy in patients with relapsing-remitting multiple sclerosis: a systematic review and meta-analysis.

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    Georgios Tsivgoulis

    Full Text Available The aim of the present meta-analysis was to evaluate the effect of disease-modifying drugs (DMD on brain atrophy in patients with relapsing-remitting multiple sclerosis (RRMS using available randomized-controlled trial (RCT data.We conducted a systematic review and meta-analysis according to PRISMA guidelines of all available RCTs of patients with RRMS that reported data on brain volume measurements during the study period.We identified 4 eligible studies, including a total of 1819 RRMS patients (71% women, mean age 36.5 years, mean baseline EDSS-score: 2.4. The mean percentage change in brain volume was found to be significantly lower in DMD versus placebo subgroup (standardized mean difference: -0.19; 95%CI: -0.27--0.11; p<0.001. We detected no evidence of heterogeneity between estimates (I2 = 30%, p = 0.19 nor publication bias in the Funnel plots. Sensitivity analyses stratifying studies according to brain atrophy neuroimaging protocol disclosed no evidence of heterogeneity (p = 0.16. In meta-regression analyses, the percentage change in brain volume was found to be inversely related with duration of observation period in both DMD (meta-regression slope = -0.03; 95% CI: -0.04--0.02; p<0.001 and placebo subgroups (meta-regression slope = -0.05; 95% CI: -0.06--0.04; p<0.001. However, the rate of percentage brain volume loss over time was greater in placebo than in DMD subgroup (p = 0.017, ANCOVA.DMD appear to be effective in attenuating brain atrophy in comparison to placebo and their benefit in delaying the rate of brain volume loss increases linearly with longer treatment duration.

  18. Brain tissue banking for stem cells for our future.

    Science.gov (United States)

    Palmero, Emily; Palmero, Sheryl; Murrell, Wayne

    2016-12-19

    In our lab we study neurogenesis and the development of brain tumors. We work towards treatment strategies for glioblastoma and towards using autologous neural stem cells for tissue regeneration strategies for brain damage and neurodegenerative disorders. It has been our policy to try to establish living cell cultures from all human biopsy material that we obtain. We hypothesized that small pieces of brain tissue could be cryopreserved and that live neural stem cells could be recovered at a later time. DMSO has been shown to possess a remarkable ability to diffuse through cell membranes and pass into cell interiors. Its chemical properties prevent the formation of damaging ice crystals thus allowing cell storage at or below -180 C. We report here a protocol for successful freezing of small pieces of tissue derived from human brain and human brain tumours. Virtually all specimens could be successfully revived. Assays of phenotype and behaviour show that the cell cultures derived were equivalent to those cultures previously derived from fresh tissue.

  19. 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.

  20. Cavernous angioma of brain stem mimicking multiple sclerosis.

    Science.gov (United States)

    Honczarenko, K; Fryze, C; Nowacki, P; Osuch, Z; Grzelec, H; Fabian, A

    1995-01-01

    A 14-year-old boy was admitted to our Department due to peripheral palsy of right VII and bilateral of the VI cranial nerves, spasticity, cerebellar symptoms as well as to dysphagia and dysarthria. In general, he was hospitalized 13 times because of the disease of a relapsing-remitting and next progressive course. He died 31 years after onset of the disease. Multiple sclerosis was diagnosed. Brain autopsy revealed tumor involving almost all brain stem structures and a part of right cerebellar hemisphere. Histologically, cavernous angioma was diagnosed.

  1. Structural brain changes in chronic pain reflect probably neither damage nor atrophy.

    Directory of Open Access Journals (Sweden)

    Rea Rodriguez-Raecke

    Full Text Available Chronic pain appears to be associated with brain gray matter reduction in areas ascribable to the transmission of pain. The morphological processes underlying these structural changes, probably following functional reorganisation and central plasticity in the brain, remain unclear. The pain in hip osteoarthritis is one of the few chronic pain syndromes which are principally curable. We investigated 20 patients with chronic pain due to unilateral coxarthrosis (mean age 63.25±9.46 (SD years, 10 female before hip joint endoprosthetic surgery (pain state and monitored brain structural changes up to 1 year after surgery: 6-8 weeks, 12-18 weeks and 10-14 month when completely pain free. Patients with chronic pain due to unilateral coxarthrosis had significantly less gray matter compared to controls in the anterior cingulate cortex (ACC, insular cortex and operculum, dorsolateral prefrontal cortex (DLPFC and orbitofrontal cortex. These regions function as multi-integrative structures during the experience and the anticipation of pain. When the patients were pain free after recovery from endoprosthetic surgery, a gray matter increase in nearly the same areas was found. We also found a progressive increase of brain gray matter in the premotor cortex and the supplementary motor area (SMA. We conclude that gray matter abnormalities in chronic pain are not the cause, but secondary to the disease and are at least in part due to changes in motor function and bodily integration.

  2. Spatial patterns of brain amyloid-beta burden and atrophy rate associations in mild cognitive impairment

    NARCIS (Netherlands)

    Tosun, Duygu; Schuff, Norbert; Mathis, Chester A.; Jagust, William; Weiner, Michael W.; Saradha, A.; Abdi, Herve; Abdulkadir, Ahmed; Abeliovich, Asa; Abellan van Kan, Gabor; Abner, Erin; Acharya, Deepa; Agrusti, Antonella; Agyemang, Alex; Ahdidan, Jamila; Ahmed, Shiek; Ahn, Jae Eun; Aisen, Paul; Aksu, Yaman; Al-Akhras, Mousa; Alarcon, Marcelo; Alberca, Roman; Alexander, Gene; Alexander, Daniel; Alin, Aylin; Almeida, Fabio; Amlien, Inge; Anand, Shyam; Anderson, Dallas; Andrew, Marilee; Angersbach, Steve; Anjum, Ayesha; Aoyama, Eiji; Arfanakis, Konstantinos; Armor, Tom; Arnold, Steven; Arunagiri, Vidhya; Asatryan, Albert; Ashe-McNalley, Cody; Ashiga, Hirokazu; Assareh, Arezoo; Le Page, Aurelie; Avants, Brian; Avinash, Gopal; Aviv, Richard; Awasthi, Sukrati; Ayan-Oshodi, Mosun; Babic, Tomislav; Baek, Young; Bagci, Ulas; Bai, Shuyang; Baird, Geoffrey; Baker, John; Banks, Sarah; Bard, Jonathan; Barnes, Josephine; Bartlett, Jonathan; Bartzokis, George; Barua, Neil; Bauer, Corinna; Bayley, Peter; Beck, Irene; Becker, James; Becker, J. Alex; Beckett, Laurel; Bednar, Martin; Beg, Mirza Faisal; Bek, Stephan; Belaroussi, Boubakeur; Belmokhtar, Nabil; Bernard, Charlotte; Bertram, Lars; Bhaskar, Uday; Biffi, Alessandro; Bigler, Erin; Bilgic, Basar; Bishop, Courtney; Bittner, Daniel; Black, Ronald; Bogorodzki, Piotr; Bokde, Arun; Bonner-Jackson, Aaron; Boppana, Madhu; Bourgeat, Pierrick; Bowes, Mike; Bowman, DuBois; Bowman, Gene; Braskie, Meredith; Braunewell, Karl; Breitner, Joihn; Bresell, Anders; Brewer, James; Brickman, Adam; Britschgi, Markus; Broadbent, Steve; Brogren, Jacob; Brooks, David; Browndyke, Jeffrey; Brunton, Simon; Buchert, Ralph; Buchsbaum, Monte; Buckley, Chris; Buerger, Katharina; Burger, Cyrill; Burnham, Samantha; Burns, Jeffrey; Burton, David; Butman, John; Cabeza, Rafael; Cairns, Nigel; Callhoff, Johanna; Calvini, Piero; Cantillon, Marc; Capella, Heraldo; Carbotti, Angela; Cardona-Sanclemente, Luis Eduardo; Carle, Adam; Carmasin, Jeremy; Carranza-Ath, Fredy; Casabianca, Jodi; Casanova, Ramon; Cash, David; Cedarbaum, Jesse; Cella, Massimo; Celsis, Pierre; Chanu, Pascal; Chao, Linda; Charil, Arnaud; Chemali, Zeina; Chen, Rong; Chen, Jake; Chen, Gennan; Chen, Wei; Chen, Kewei; Chen, Shuzhong; Chen, Minhua; Cheng, Wei-Chen; Cherkas, Yauheniya; Chertkow, Howard; Cheung, Charlton; Cheung, Vinci; Chiang, Gloria; Chiba, Koji; Chin, Simon; Chisholm, Jane; Cho, Youngsang; Choe, John; Choubey, Suresh; Chowbina, Sudhir; Christensen, Anette Luther; Clark, David; Clark, Chris; Clarkson, Matt; Clayton, David; Clunie, David; Coen, Michael; Coimbra, Alexandre; Compton, David; Coppola, Giovanni; Coulin, Samuel; Cover, Keith S.; Crane, Paul; Crans, Gerald; Croop, Robert; Crowther, Daniel; Crum, William; Cui, Yue; Curry, Charles; Curtis, Steven; Cutter, Gary; Daiello, Lori; Dake, Michael; Dale, Anders; Daliri, Mohammad Reza; Damato, Vito Domenico; Darby, Eveleen; Darkner, Sune; Davatzikos, Christos; Dave, Jay; David, Renaud; DavidPrakash, Bhaskaran; Davidson, Julie; de Bruijne, Marleen; de Meyer, Geert; de Nunzio, Giorgio; Decarli, Charles; Dechairo, Bryan; DeDuck, Kristina; Dehghan, Hossein; Dejkam, Arsalan; Delfino, Manuel; Della Rosa, Pasquale Anthony; Dellavedova, Luca; Delpassand, Ebrahim; Delrieu, Julien; DeOrchis, Vincent; Depy Carron, Delphine; deToledo-Morrell, Leyla; Devanand, Davangere; Devanarayan, Viswanath; DeVous, Michael; Diaz-Arrastia, Ramon; Bradford, Dickerson; Ding, Xiaobo; Dinov, Ivo; Dobson, Howard; Dodge, Hiroko; Donohue, Michael; Dore, Vincent; Dorflinger, Ernest; Dowling, Maritza; Duan, Xujun; Dubal, Dena; Duchesne, Simon; Duff, Kevin; Dukart, Jrgen; Durazzo, Timothy; Dykstra, Kevin; Earl, Nancy; Edula, Goutham; Ekin, Ahmet; Elcoroaristizabal, Xabier; Emahazion, Tesfai; Engelman, Corinne; Epstein, Noam; Erten-Lyons, Deniz; Eskildsen, Simon; Falcone, Guido; Fan, Lingzhong; Fan, Yong; Farahibozorg, Seyedehrezvan; Farb, Norman; Farnum, Michael; Farrer, Lindsay; Farzan, Ali; Faux, Noel; Feldman, Betsy; Feldman, Howard; Feldman, Susan; Fennema-Notestine, Christine; Fernandes, Michel; Fernandez, Elsa; Ferrarini, Luca; Ferreira, Manuel Joao; Ferrer, Eugene; Figurski, Michal; Filipovych, Roman; Fillit, Howard; Finch, Stephen; Finlay, Daniel; Fiot, Jean-Baptiste; Flenniken, Derek; Fletcher, P. Thomas; Fletcher, Evan; Flynn Longmire, Crystal; Focke, Niels; Forman, Mark; Forsythe, Alan; Fox, Steven; Fox-Bosetti, Sabrina; Francis, Alexander L.; Franco-Villalobos, Conrado; Franko, Edit; Freeman, Stefanie; Friedrich, Christoph M.; Friesenhahn, Michel; Frings, Lars; Frisoni, Giovanni; Fritzsche, Klaus; Fujimoto, Yoko; Fujiwara, Ken; Fullerton, Terence; Furney, Simon; Gallins, Paul; Galvin, Ben; Gamst, Anthony; Gan, Ke; Garcia, Maria Teresa; Garg, Gaurav; Gaser, Christian; Gastineau, Edward; Gauthier, Serge; Gavett, Brandon; Gavidia, Giovana; Gazdzinski, Stefan; Ge, Qi; Ge, Tian; Gemme, Gianluca; Geraci, Joseph; Ghassabi, Zeinab; Gieschke, Ronald; Gil, Juan E.; Gill, Ryan; Gitelman, Darren; Gleason, Carey; Glymour, M. Maria; Godbey, Michael; Goghari, Vina; Gold, Michael; Goldberg, Terry; Goldman, Jennifer; Gomeni, Roberto; Gong, Shangwenyan; Gonzales, Celedon; Goodro, Robert; Gordon, Brian; Gore, Chris; Gorriz, Juan Manuel; Grachev, Igor; Grandey, Emily; Grasela, Thaddeus; Gratt, Jeremy; Gray, Katherine; Greenberg, Barry; Gregg, Keith; Gregory, Erik; Greicius, Michael; Greve, Douglas; Grill, Joshua; Gross, Alden; Gross, Alan; Guignot, Isabelle; Guo, Jeffrey; Guo, Qimiao; Guo, Hongbin; Guo, Lianghao; Habeck, Christian; Hai, Yizhen; Haight, Thaddeus; Hammarstrom, Per; Hampel, Harald; Han, Duke; Han, Jian; Han, Tony; Hanif, Muhammad; Hanna, Yousef; Hardy, Peter; Harvey, Danielle; Hasan, Md Kamrul; Hayashi, Toshihiro; Hazart, Aurelien; He, Huiguang; He, Yong; Head, Denise; Heckemann, Rolf; Heidebrink, Judith; Henderson, David; Henrard, Sebastien; Herholz, Karl; Hernandez, Monica; Herskovits, A. Zara; Hess, Christopher; Hildenbrand, Maike; Hobart, Jeremy; Hoffman, John; Holder, Daniel; Hollingworth, Paul; Holmes, Robin; Honigberg, Lee; Hoppin, Jack; Hou, Yangyang; Hsu, Ailing; Hsu, Wei-Wen; Hu, Xiaolan; Hu, Zhiwei; Hu, William; Huang, Juebin; Huang, Chien-Chih; Huang, Chingwen; Huang, Shuai; Huang, Yifan; Huang, Fude; Huang, Chun-Jung; Huang, Shu-Pang; Hubbard, Rebecca; Huentelman, Matthew; Hui, Shen; Huppertz, Hans-Jürgen; Hurko, Orest; Hurt, Stephen; Huyck, Susan; Hwang, Scott; Hyun, JungMoon; Ifeachor, Emmanuel; Iglesias, Martina; Ikari, Yasuhiko; Ikonomidou, Vasiliki; Imani, Farzin; Immermann, Fred; Inlow, Mark; Inoue, Lurdes; Insel, Philip; Irizarry, Michael; Irungu, Benson mwangi; Ishibashi, Taro; Ishii, Kenji; Ismail, Sara; Ismail, Shahina; Ito, Kaori; Iturria-Medina, Yasser; Iwatsubo, Takeshi; Jacobson, Mark; Jacqmin, Philippe; Jafari, Aria; Jafari-Khouzani, Kourosh; Jaffe, Carl; Jara, Hernan; Jasperse, Bas; Jedynak, Bruno; Jefferson, Angela; Jennings, J. Richard; Jessen, Walter; Jia, Fucang; Jiang, Tianzi; Jing, Huang; Johnson, Julene; Johnson, Sterling; Johnson, David K.; Jones, Richard; Juengling, Freimut; Juh, Rahyeong; Julin, Per; Kadish, Bill; Kahle-Wrobleski, Kristin; Kallam, Hanimi Reddy; Kamboh, M. Ilyas; Kaneko, Tomoki; Kaneta, Tomohiro; Kang, Ju Hee; Karageorgiou, Elissaios; Karantzoulis, Stella; Karlawish, Jason; Katz, Elyse; Kaushik, Sandeep S.; Kauwe, John; Kawakami, Hirofumi; Kazimipoor, Borhan; Kelleher, Thomas; Kennedy, Richard; Kerchner, Geoffrey; Kerrouche, Nacer; Khalil, Iya; Khalil, Andre; Killeen, Neil; Killiany, Ron; Kim, Jong Hun; Kim, Heeyoung; Kim, Ana; Kim, Yeonhee; Kim, Hyoungkyu; Kim, Seongkyun; Kim, Hyewon; Kimberg, Daniel; Kimura, Tokunori; King, Richard; Kirby, Justin; Kirsch, Wolff; Klimas, Michael; Kline, Richard; Kling, Mitchel; Klopfenstein, Erin; Koikkalainen, Juha; Kokomoor, Anders; Kolasny, Anthony; Koppel, Jeremy; Korolev, Igor; Kotran, Nickolas; Kouassi, Alex; Kowalczyk, Adam; Kozma, Lynn; Krams, Michael; Kratzer, Martina; Kuceyeski, Amy; Kuhn, Felix Pierre; Kumar, Sreedhar; Kuo, Hsun Ting; Kuo, Julie; Kurosawa, Ken; Kwon, Oh Hun; Labrish, Catherine; Laforet, Genevieve; Lai, Song; Lakatos, Anita; Lam, On Ki; Lampron, Antoine; Landau, Susan; Landen, Jaren; Lane, Richard; Langbaum, Jessica; Langford, Dianne; Lanius, Vivian; Laxamana, Joel; Le, Trung; Leahy, Richard; Lee, Jong-Min; Lee, Vita; Lee, Joseph H.; Lee, Grace; Lee, Dongsoo; Lee, Noah; Lefkimmiatis, Stamatis; Lemaitre, Herve; Lenfant, Pierre; Lenz, Robert; Leoutsakos, Jeannie-Marie; Lester, Gayle; Levey, Allan; Li, Shi-jiang; Li, Shanshan; Li, Wenjun; Li, Chin-Shang; Li, Xiaodong; Li, Rui; Li, Ming; Li, Lexin; Li, Jinhe; Li, Yi; Li, Quanzheng; Li, Gang; Liang, Kuchang; Liang, Peipeng; Liang, Lichen; Liao, Yuan-Lin; Lin, Ling-chih; Lin, Lan; Lin, Mingkuan; Lin, Ai-Ling; Liu, Songling; Liu, Yuan; Liu, Tianming; Liu, Meijie; Liu, Xiuwen; Liu, Li; Liu, Honggang; Liu, Pu; Liu, Tao; Liu, Sophia; Liu, Dazhong; Lo, Raymond; Lobanov, Victor; Loewenstein, David; Logovinsky, Veronika; Long, Xiaojing; Long, Ziyi; Looi, Jeffrey; Lu, Po-Haong; Lukic, Ana; Lull, Juan J.; Luo, Xiongjian; Lynch, John; Ma, Lei; Mackin, Scott; Mada, Marius; Magda, Sebastian; Maglio, Silvio; Maikusa, Norihide; Mak, Henry Ka-Fung; Malave, Vicente; Maldjian, Joseph; Mandal, Pravat; Mangin, Jean-Francois; Manjon, Jose; Mantri, Ninad; Manzour, Amir; Marambaud, Philippe; Marchewka, Artur; Marek, Kenneth; Markind, Samuel; Marshall, Gad; Martinez Torteya, Antonio; Mather, Mara; Mathis, Chester; Matoug, Sofia; Matsuo, Yoshiyuki; Mattei, Peter; Matthews, Dawn; McArdle, John; McCarroll, Steven; McEvoy, Linda; McGeown, William; McGonigle, John; McIntyre, John; McLaren, Donald; McQuail, Joseph; Meadowcroft, Mark; Meda, Shashwath; Mehta, Nirav; Melie-Garcia, Lester; Melrose, Rebecca; Mendonca, Brian; Menendez, Manuel; Meredith, Jere; Merrill, David; Mesulam, Marek-Marsel; Metti, Andrea; Meyer, Carsten; Mez, Jesse; Mickael, Guedj; Miftahof, Roustem; Mikhno, Arthur; Miller, David; Millikin, Colleen; Min, Ye; Mirza, Mubeena; Mistridis, Panagiota; Mitchell, Meghan; Mitsis, Effie; Mohan, Ananth; Moore, Dana; Moradi Birgani, Parmida; Moratal, David; Morimoto, Bruce; Mormino, Elizabeth; Mortamet, Benedicte; Moscato, Pablo; Mueller, Kathyrne; Mueller, Susanne; Mueller, Notger; Mukherjee, Shubhabrata; Mulder, Emma; Murayama, Shigeo; Murphy, Michael; Murray, Brian; Musiek, Erik; Myers, Amanda; Najafi, Shahla; Nazarparvar, Babak; Nazeri, Arash; Nettiksimmons, Jasmine; Neu, Scott; Ng, Yen-Bee; Nguyen, Nghi; Nguyen Xuan, Tuong; Nichols, Thomas; Nicodemus, Kristin; Niecko, Timothy; Nielsen, Casper; Notomi, Keiji; Nutakki, Gopi Chand; O'Bryant, Sid; O'Neil, Alison; Obisesan, Thomas; Oh, Dong Hoon; Oh, Joonmi; Okonkwo, Ozioma; Olde Rikkert, Marcel; Olmos, Salvador; Ortner, Marion; Ostrowitzki, Susanne; Oswald, Annahita; Ott, Brian; Ourselin, Sebastien; Ouyang, Gaoxiang; Paiva, Renata; Pan, Zhifang; Pande, Yogesh; Pardo, Jose; Pardoe, Heath; Park, Hyunjin; Park, Lovingly; Park, Moon Ho; Park, Sang hyun; Park, Kee Hyung; Park, Sujin; Parsey, Ramin; Parveen, Riswana; Paskavitz, James; Patel, Yogen; Patil, Manasi; Pawlak, Mikolaj; Payoux, Pierre; Pearson, Jim; Peavy, Guerry; Pell, Gaby; Peng, Yahong; Pennec, Xavier; Pepin, Jean louis; Perea, Rodrigo; Perneczky, Robert; Petitti, Diana; Petrella, Jeffrey; Peyrat, Jean-Marc; Pezoa, Jorge; Pham, Chi-Tuan; Phillips, Justin; Phillips, Nicole; Pierson, Ronald; Piovezan, Mauro; Podhorski, Adam; Pollari, Mika; Pontecorvo, Michael; Poppenk, Jordan; Posner, Holly; Potkin, Steven; Potter, Guy; Potter, Elizabeth; Poulin, Stephane; Prasad, Gautam; Prenger, Kurt; Prince, Jerry; Priya, Anandh; Puchakayala, Shashidhar Reddy; Qiu, Ruolun; Qiu, Anqi; Qiu, Wendy; Qualls, Constance Dean; Rabie, Huwaida; Rajeesh, Rajeesh; Rallabandi, V. P. Subramanyam; Ramage, Amy; Randolph, Christopher; Rao, Anil; Rao, Divya; Raubertas, Richard; Ray, Debashis; Razak, Hana; Redolfi, Alberto; Reed, Bruce; Reid, Andrew; Reilhac, Anthonin; Reinsberger, Claus; Restrepo, Lucas; Retico, Alessandra; Richards, John; Riddle, William; Ries, Michele; Rincon, Mariano; Rischall, Matt; Rizk-Jackson, Angela; Robieson, Weining; Rocha-Rego, Vanessa; Rogalski, Emily; Rogers, Elizabeth; Rojas, Ignacio; Rojas Balderrama, Javier; Romero, Klaus; Rorden, Chris; Rosand, Jonathan; Rosen, Allyson; Rosen, Ori; Rosenberg, Paul; Ross, David; Roubini, Eli; Rousseau, François; Rowe, Christopher; Rubin, Daniel; Rubright, Jonathan; Ruiz, Agustin; Rusinek, Henry; Ryan, Laurie; Saad, Ahmed; Sabbagh, Marway; Sabuncu, Mert; Sachs, Michael; Sadeghi, Ali; Said, Yasmine; Saint-Aubert, Laure; Sakata, Muneyuki; Salat, David; Salmon, David; Salter, Hugh; Samwald, Matthias; Sanchez, Luciano; Sanders, Elizabeth; Sanjo, Nobuo; Sarnel, Haldun; Sato, Hajime; Sato, Shinji; Saumier, Daniel; Savio, Alexandre; Sawada, Ikuhisa; Saykin, Andrew; Schaffer, J. David; Scharre, Douglas; Schegerin, Marc; Schlosser, Gretchen; Schmand, Ben; Schmansky, Nick; Schmidt, Mark; Schmidt-Wilcke, Tobias; Schneider, Lon; Schramm, Hauke; Schuerch, Markus; Schwartz, Eben; Schwartz, Craig; Schwarz, Adam; Seethamraju, Ravi; Seixas, Flavio; Selnes, Per; Senjem, Matthew; Senlin, Wang; Seo, Sang Won; Sethuraman, Gopalan; Sevigny, Jeffrey; Sfikas, Giorgos; Sghedoni, Roberto; Shah, Said Khalid; Shahbaba, Babak; Shams, Soheil; Shattuck, David; Shaw, Leslie; Sheela, Jaba; Shen, Weijia; Shen, Qian; Shera, David; Sherman, John; Sherva, Richard; Shi, Feng; Shukla, Vinay; Shuler, Catherine; Shulman, Joshua; Siegel, Rene; Siemers, Eric; Silveira, Margarida; Silver, Michael; Silverman, Daniel; Sim, Ida; Simmons, Andy; Simoes, Rita; Simon, Melvin; Simpson, Ivor; Singh, Simer Preet; Singh, Nikhil; Siuciak, Judy; Sjogren, Niclas; Skinner, Jeannine; Skup, Martha; Small, Gary; Smith, Michael; Smith, Benjamin; Smith, Charles; Smyth, Timothy; Snow, Sarah; Soares, Holly; Soldea, Octavian; Solomon, Paul; Solomon, Alan; Som, Subhojit; Song, Changhong; Song, Mingli; Sosova, Iveta; Soudah, Eduardo; Soydemir, Melih; Spampinato, Maria Vittoria; Spenger, Christian; Sperling, Reisa; Spiegel, Rene; Spies, Lothar; Squarcia, Sandro; Squire, Larry; Staff, Roger; Stern, Yaakov; Straw, Jack; Stricker, Nikki; Strittmatter, Stephen; Stühler, Elisabeth; Styren, Scot; Subramanian, Vijayalakshmi; Sugishita, Morihiro; Sukkar, Rafid; Sun, Jia; Sun, Ying; Sun, Yu; Sundell, Karen; Suri, Muhammad; Suzuki, Akiyuki; Svetnik, Vladimir; Swan, Melanie; Takahasi, Tetsuhiko; Takeuchi, Tomoko; Tanaka, Shoji; Tanchi, Chaturaphat; Tancredi, Daniel; Tao, Wenwen; Tao, Dacheng; Taylor-Reinwald, Lisa; Teng, Edmond; Terlizzi, Rita; Thames, April; Thiele, Frank; Thomas, Benjamin; Thomas, Ronald; Thompson, Paul; Thompson, Wesley; Thornton-Wells, Tricia; Thorvaldsson, Valgeir; Thurfjell, Lennart; Titeux, Laurence; Tokuda, Takahiko; Toledo, Juan B.; Tolli, Tuomas; Toma, Ahmed; Tomita, Naoki; Toro, Roberto; Torrealdea, Patxi; Tousian, Mona; Toussaint, Paule; Toyoshiba, Hiroyoshi; Tractenberg, Rochelle E.; Trittschuh, Emily; Trojanowski, John; Truran, Diana; Tsechpenakis, Gavriil; Tucker-Drob, Elliot; Tufail, Ahsan; Tung, Joyce; Turken, And; Ueda, Yoji; Ullrich, Lauren; Umadevi Venkataraju, Kannan; Umar, Nisser; Uzunbas, Gokhan; van de Nes, Joseph; van der Brug, Marcel; van Horn, John; van Leemput, Koen; van Train, Kenneth; van Zeeland, Ashley; Vasanawala, Minal; Vemuri, Prashanthi; Verwaerde, Philippe; Videbaek, Charlotte; Vidoni, Eric; Villanueva-Meyer, Javier; Visser, Pieter Jelle; Vitolo, Ottavio; Vounou, Maria; Wade, Sara; Walhovd, Kristine B.; Wan, Hong; Wang, Huanli; Wang, Yongmei Michelle; Wang, Yalin; Wang, Angela; Wang, Lei; Wang, Yue; Wang, Xu; Wang, Ze; Wang, Yaping; Wang, Tiger; Wang, Alex; Wang, Huali; Wang, Li-San; Wang, Wei; Wang, Li; Ward, Michael; Warfield, Simon; Waring, Stephen; Watanabe, Toshiyuki; Webb, David; Wei, Lili; Weiner, Michael; Wen, Shu-Hui; Wenjing, Li; Wenzel, Fabian; Westlye, Lars T.; Whitcher, Brandon; Whitlow, Christopher; Whitwell, Jennifer; Wilhelmsen, Kirk; Williams, David; Wilmot, Beth; Wimsatt, Matt; Wingo, Thomas; Wiste, Heather; Wolfson, Tanya; Wolke, Ira; Wolz, Robin; Woo, Jongwook; Woo, Ellen; Woods, Lynn; Worth, Andrew; Worth, Eric; Wouters, Hans; Wu, Teresa; Wu, Yi-Gen; Wu, Liang; Wu, Xiaoling; Wyman, Bradley; Wyss-Coray, Tony; Xiao, Guanghua; Xiao, Liu; Xie, Sharon; Xu, Shunbin; Xu, Ye; Xu, Yi-Zheng; Xu, Guofan; Xu, Jun; Yamane, Tomohiko; Yamashita, Fumio; Yan, Yunyi; Yan, Pingkun; Yang, Eric; Yang, Jinzhong; Yang, Qing X.; Yang, Zijiang; Yang, Guang; Yang, Zhitong; Yang, Wenlu; Ye, Liang; Ye, Byoung Seok; Ye, Jieping; Ye, Jong; Yee, Laura; Yesavage, Jerome; Ying, Song; Yoo, Bongin; Young, Jonathan; Yu, Shiwei; Yu, Dongchuan; Yuan, Guihong; Yuan, Kai; Yushkevich, Paul; Zaborszky, Laszlo; Zagorodnov, Vitali; Zagorski, Michael; Zawadzki, Rezi; Zeitzer, Jamie; Zelinski, Elizabeth; Zhang, Kurt; Zhang, Huixiong; Zhang, Tianhao; Zhang, Xin; Zhang, Ping; Zhang, Bin; Zhang, Jing; Zhang, Linda; Zhang, Lijun; Zhang, Zhiguo; Zhao, Qinying; Zhao, Jim; Zhao, Peng; Zhen, Xiantong; Zheng, Yuanjie; Zhijun, Yao; Zhou, Bin; Zhou, Sheng; Zhu, Wen; Zhu, Hongtu; Zhu, Wanlin; Zilka, Samantha; Zito, Giancarlo; Zou, Heng

    2011-01-01

    Amyloid-β accumulation in the brain is thought to be one of the earliest events in Alzheimer's disease, possibly leading to synaptic dysfunction, neurodegeneration and cognitive/functional decline. The earliest detectable changes seen with neuroimaging appear to be amyloid-β accumulation detected by

  3. Olivary degeneration after cerebellar or brain stem haemorrhage: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, A. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan) Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Hasuo, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Uchida, K. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Matsumoto, S. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Tsukamoto, Y. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Ohno, M. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Masuda, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan))

    1993-05-01

    Magnetic resonance (MR) images of seven patients with olivary degeneration caused by cerebellar or brain stem haemorrhages were reviewed. In four patients with cerebellar haemorrhage, old haematomas were identified as being located in the dentate nucleus; the contralateral inferior olivary nuclei were hyperintense on proton-density- and T2-weighted images. In two patients with pontine haemorrhages, the old haematomas were in the tegmentum and the ipsilateral inferior olivary nuclei, which were hyperintense. In one case of midbrain haemorrhage, the inferior olivary nuclei were hyperintense bilaterally. The briefest interval from the ictus to MRI was 2 months. Hypertrophic olivary nuclei were observed only at least 4 months after the ictus. Olivary degeneration after cerebellar or brain stem haemorrhage should not be confused with ischaemic, neoplastic, or other primary pathological conditions of the medulla. (orig.)

  4. Application of contact laser in microsurgery of brain stem tumors

    Directory of Open Access Journals (Sweden)

    Jian-wen GU

    2011-02-01

    Full Text Available Objective To explore the therapeutic efficacy of a new type sapphire contact laser using wavelength-shifting technique on microsurgery of brain stem tumors.Methods The clinical data were retrospectively analyzed of 23 patients(13 males and 10 females,aged 6 to 69 years with an average of 38 years,and the duration of disease was 14 to 36 months with average of 22 months with brain stem tumor admitted from Mar.2006 to May 2010.The major symptoms of the patients were cranial nerve impairment,cerebellum function impairment or paralysis.All patients received microsurgical resection of brain stem tumor using sapphire contact laser through median suboccipital incision and posterior brain stem approach,and the tumors were resected with precision operation and vaporization and ablation.Results Of the 23 patients,4 were with glioma,15 with cavernous angioma,2 with angioreticuloma and 2 with metastatic tumor.Total resection was achieved in 15 cases,while subtotal resection(more than 80% in 6 cases.Intraoperative hemorrhage was less and no intraoperative blood transfusion was required.A 6-months follow-up showed symptoms recovered in 15 patients,improved in 4,unchanged in 2,and worsen in 1.One patient died of recurrence of tumor.No postoperative intracranial infection was occurred,and 2 patients were undergone tracheotomy after operation.The average hospital stay was 15d.Conclusion The contact laser can precisely dissect and vaporize the tumors,increase the resection rate,reduce intraoperative hemorrhage and accessory injuries,and has a clear and definite effect.

  5. Copine1 regulates neural stem cell functions during brain development.

    Science.gov (United States)

    Kim, Tae Hwan; Sung, Soo-Eun; Cheal Yoo, Jae; Park, Jae-Yong; Yi, Gwan-Su; Heo, Jun Young; Lee, Jae-Ran; Kim, Nam-Soon; Lee, Da Yong

    2018-01-01

    Copine 1 (CPNE1) is a well-known phospholipid binding protein in plasma membrane of various cell types. In brain cells, CPNE1 is closely associated with AKT signaling pathway, which is important for neural stem cell (NSC) functions during brain development. Here, we investigated the role of CPNE1 in the regulation of brain NSC functions during brain development and determined its underlying mechanism. In this study, abundant expression of CPNE1 was observed in neural lineage cells including NSCs and immature neurons in human. With mouse brain tissues in various developmental stages, we found that CPNE1 expression was higher at early embryonic stages compared to postnatal and adult stages. To model developing brain in vitro, we used primary NSCs derived from mouse embryonic hippocampus. Our in vitro study shows decreased proliferation and multi-lineage differentiation potential in CPNE1 deficient NSCs. Finally, we found that the deficiency of CPNE1 downregulated mTOR signaling in embryonic NSCs. These data demonstrate that CPNE1 plays a key role in the regulation of NSC functions through the activation of AKT-mTOR signaling pathway during brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Brain SPET abnormalities in Alzheimer's disease before and after atrophy correction

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Hiroshi; Kanetaka, Hidekazu; Ohnishi, Takashi; Imabayashi, Etsuko; Katoh, Asako; Tanaka, Fumiko [Department of Radiology, National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, 187-8551, Tokyo (Japan); Asada, Takashi [Department of Neuropsychiatry, Institute of Clinical Medicine, University of Tsukuba, Ibaraki (Japan); Nakano, Seigo [Department of Geriatric Medicine, National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry, Kodaira, Tokyo (Japan)

    2002-11-01

    The aim of this study was to determine which brain structures show the greatest influence of partial volume effects (PVE) in single-photon emission tomography (SPET) studies on Alzheimer's disease (AD). Brain perfusion SPET was performed in 30 patients with probable AD and 62 age-matched healthy volunteers. SPET images were corrected for PVE using grey matter volume segmented from magnetic resonance images. The most prominent changes after PVE correction were observed in the medial temporal structures. The PVE correction revealed a selective decrease in regional cerebral blood flow (rCBF) in the parahippocampal gyrus of AD without rCBF decreases in the hippocampus, which had been observed before correction. This correction seems to be essential in order to achieve accurate measurements of rCBF in SPET, which has limited spatial resolution. (orig.)

  7. Electromyographic and computed tomographic findings in five patients with monomelic spinal muscular atrophy

    NARCIS (Netherlands)

    de Visser, M.; Ongerboer de Visser, B. W.; Verbeeten, B.

    1988-01-01

    Five patients with monomelic spinal muscular atrophy are described. Clinical features included insidious onset of wasting and weakness of one limb, lack of involvement of the cranial nerves, brain stem, pyramidal tracts and sensory system, and a stable condition over a period of 4-20 years. Clinical

  8. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Wang, Xiaoqing; Yu, Xiaowen; Xie, Chong; Tan, Zijian; Tian, Qi; Zhu, Desheng; Liu, Mingyuan; Guan, Yangtai

    2016-05-01

    Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function.

  9. Case report of optic atrophy in Dentatorubropallidoluysian Atrophy (DRPLA).

    Science.gov (United States)

    Silver, Michael R; Sethi, Kapil D; Mehta, Shyamal H; Nichols, Fenwick T; Morgan, John C

    2015-12-18

    Dentatorubropallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disease that is associated with numerous movement disorders. Ocular problems also occur with DRPLA with reports of corneal endothelial degeneration in some patients living with the disease. We report a new visual problem associated with DRPLA, optic atrophy. A 47 year-old man presented complaining of progressive visual loss associated with optic atrophy on ophthalmological evaluation. He gradually developed a progressive ataxia with dystonia. Brain MRI revealed a diffuse leukoencephalopathy. Genetic analysis revealed 62 CAG repeats in one allele of the DRPLA gene and he was diagnosed with DRPLA. Optic atrophy should be included in the clinical spectrum of DRPLA.

  10. A longitudinal observational study of brain atrophy rate reflecting four decades of multiple sclerosis: a comparison of serial 1D, 2D, and volumetric measurements from MRI images

    Energy Technology Data Exchange (ETDEWEB)

    Martola, Juha; Zhang, Yi; Aspelin, Peter; Kristoffersen Wiberg, Maria [Karolinska Institutet, Division of Radiology, Department of Clinical Science, Intervention, and Technology, Stockholm (Sweden); Bergstroem, Jakob [Karolinska Institutet, The Medical Statistics Unit, Department of Learning, Informatics, Management and Ethics (LIME), Stockholm (Sweden); Fredrikson, Sten; Stawiarz, Leszek; Hillert, Jan [Karolinska Institutet, Division of Neurology, Department of Clinical Neuroscience, Stockholm (Sweden); Flodmark, Olof; Lilja, Anders [Karolinska University Hospital, Department of Neuroradiology, Department of Clinical Neuroscience, Stockholm (Sweden); Ekbom, Anders [Karolinska Institutet, Clinical Epidemiology Unit, Stockholm (Sweden)

    2010-02-15

    Multiple sclerosis (MS) has a variable progression with an early onset of atrophy. Individual longitudinal radiological evaluations (over decades) are difficult to perform due to the limited availability of magnetic resonance imaging (MRI) in the past, patients lost in follow-up, and the continuous updating of scanners. We studied a cohort with widespread disease duration at baseline. The observed individual atrophy rates over time of 10 years represented four decades of disease span. Thirty-seven MS patients (age range 24-65 years with disease duration 1-33 years) were consecutively selected and evaluated with MRI at baseline 1995 and in 1996. They were followed up for a decade (mean of 9.25 years, range 7.3-10 years) up to 2003-2005. Brain parenchymal volume and volumes of the supratentorial ventricles were analyzed with semi-automated volumetric measurements at three time points (1995, 1996, and 2003-2005). Volumetric differences were found over shorter periods of time (1-7 months); however, differences vanished by the end of follow-up. A uniform longitudinal decrease in brain volume and increase in ventricle volumes were found. Frontal horn width (1D) correlated strongest to 3D measures. No statistical differences of atrophy rates between MS courses were found. Supratentorial ventricular volumes were associated with disability and this association persisted during follow-up. Despite variable clinical courses, the degenerative effects of MS progression expressed in brain atrophy seem to uniformly progress over longer periods of time. These volumetric changes can be detected using 1D and 2D measurements performed on a routine PACS workstation. (orig.)

  11. Brain docosahexaenoic acid [DHA] incorporation and blood flow are increased in chronic alcoholics: a positron emission tomography study corrected for cerebral atrophy.

    Directory of Open Access Journals (Sweden)

    John C Umhau

    Full Text Available Chronic alcohol dependence has been associated with disturbed behavior, cerebral atrophy and a low plasma concentration of docosahexaenoic acid (DHA, 22∶6n-3, particularly if liver disease is present. In animal models, excessive alcohol consumption is reported to reduce brain DHA concentration, suggesting disturbed brain DHA metabolism. We hypothesized that brain DHA metabolism also is abnormal in chronic alcoholics.We compared 15 non-smoking chronic alcoholics, studied within 7 days of their last drink, with 22 non-smoking healthy controls. Using published neuroimaging methods with positron emission tomography (PET, we measured regional coefficients (K* and rates (J(in of DHA incorporation from plasma into the brain of each group using [1-(11C]DHA, and regional cerebral blood flow (rCBF using [(15O]water. Data were partial volume error corrected for brain atrophy. Plasma unesterified DHA concentration also was quantified.Mean K* for DHA was significantly and widely elevated by 10-20%, and rCBF was elevated by 7%-34%, in alcoholics compared with controls. Unesterified plasma DHA did not differ significantly between groups nor did whole brain J(in, the product of K* and unesterified plasma DHA concentration.Significantly higher values of K* for DHA in alcoholics indicate increased brain avidity for DHA, thus a brain DHA metabolic deficit vis-à-vis plasma DHA availability. Higher rCBF in alcoholics suggests increased energy consumption. These changes may reflect a hypermetabolic state related to early alcohol withdrawal, or a general brain metabolic change in chronic alcoholics.

  12. Implications of aneuploidy for stem cell biology and brain therapeutics

    Directory of Open Access Journals (Sweden)

    Sylvie eDevalle

    2012-09-01

    Full Text Available Understanding the cellular basis of neurological disorders have advanced at a slow pace, especially due to the extreme invasiveness of brain biopsying and limitations of cell lines and animal models that have been used. Since the derivation of pluripotent stem cells (PSCs, a novel source of cells for regenerative medicine and disease modeling has become available, holding great potential for the neurology field. However, safety for therapy and accurateness for modeling have been a matter of intense debate, considering that genomic instability, including the gain and loss of chromosomes (aneuploidy, has been repeatedly observed in those cells. Despite the fact that recent reports have described some degree of aneuploidy as being normal during neuronal differentiation and present in healthy human brains, this phenomenon is particularly controversial since it has traditionally been associated with cancer and disabling syndromes. It is therefore necessary to appreciate, to which extent, aneuploid pluripotent stem cells are suitable for regenerative medicine and neurological modeling and also the limits that separate constitutive from disease-related aneuploidy. In this review, recent findings regarding chromosomal instability in PSCs and within the brain will be discussed.

  13. Brain stem evoked response to forward and reversed speech in humans.

    Science.gov (United States)

    Galbraith, Gary C; Amaya, Elizabeth M; de Rivera, Jacinta M Diaz; Donan, Namee M; Duong, Mylien T; Hsu, Jeffrey N; Tran, Kim; Tsang, Lian P

    2004-09-15

    Speech stimuli played in reverse are perceived as unfamiliar and alien-sounding, even though phoneme duration and fundamental voicing frequency are preserved. Although language perception ultimately resides in the neocortex, the brain stem plays a vital role in processing auditory information, including speech. The present study measured brain stem frequency-following responses (FFR) evoked by forward and reverse speech stimuli recorded from electrodes oriented horizontally and vertically to measure signals with putative origins in auditory nerve and rostral brain stem, respectively. The vertical FFR showed increased amplitude due to forward speech. It is concluded that familiar phonological and prosodic properties of forward speech selectively activate central brain stem neurons.

  14. Integration of Subretinal Suspension Transplants of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in a Large-Eyed Model of Geographic Atrophy.

    Science.gov (United States)

    Petrus-Reurer, Sandra; Bartuma, Hammurabi; Aronsson, Monica; Westman, Sofie; Lanner, Fredrik; André, Helder; Kvanta, Anders

    2017-02-01

    Subretinal suspension transplants of human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) have the capacity to form functional monolayers in naive eyes. We explore hESC-RPE integration when transplanted in suspension to a large-eyed model of geographic atrophy (GA). Derivation of hESC-RPE was performed in a xeno-free and defined manner. Subretinal bleb injection of PBS or sodium iodate (NaIO3) was used to induce a GA-like phenotype. Suspensions of hESC-RPE were transplanted to the subretinal space of naive or PBS-/NaIO3-treated rabbits using a transvitreal pars plana technique. Integration of hESC-RPE was monitored by multimodal real-time imaging and by immunohistochemistry. Subretinal blebs of PBS or NaIO3 caused different degrees of outer neuroretinal degeneration, RPE hyperautofluorescence, focal RPE loss, and choroidal atrophy; that is, hallmark characteristics of GA. In nonpretreated naive eyes, hESC-RPE integrated as subretinal monolayers with preserved overlying photoreceptors, yet not in areas with outer neuroretinal degeneration and native RPE loss. When transplanted to eyes with PBS-/NaIO3-induced degeneration, hESC-RPE failed to integrate. In a large-eyed preclinical model, subretinal suspension transplants of hESC-RPE did not integrate in areas with GA-like degeneration.

  15. Apolipoprotein E ε4 Is Associated with Disease-Specific Effects on Brain Atrophy in Alzheimer's Disease and Frontotemporal Dementia

    National Research Council Canada - National Science Library

    Federica Agosta; Keith A. Vossel; Bruce L. Miller; Raffaella Migliaccio; Stephen J. Bonasera; Massimo Filippi; Adam L. Boxer; Anna Karydas; Katherine L. Possin; Maria Luisa Gorno-Tempini; Robert Mahley

    2009-01-01

    .... We investigated the influence of µ4 allele carrier status on the pattern of gray matter atrophy and disease severity in 51 patients with probable AD and 31 patients with behavioral variant frontotemporal dementia (bvFTD...

  16. The BRAIN Initiative Provides a Unifying Context for Integrating Core STEM Competencies into a Neurobiology Course

    OpenAIRE

    Schaefer, Jennifer E.

    2016-01-01

    The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative introduced by the Obama Administration in 2013 presents a context for integrating many STEM competencies into undergraduate neuroscience coursework. The BRAIN Initiative core principles overlap with core STEM competencies identified by the AAAS Vision and Change report and other entities. This neurobiology course utilizes the BRAIN Initiative to serve as the unifying theme that facilitates a primary emphasis ...

  17. Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    Shih-Min Wang

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS. Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.

  18. Age and Gender Effects On Auditory Brain Stem Response (ABR

    Directory of Open Access Journals (Sweden)

    Yones Lotfi

    2012-10-01

    Full Text Available Objectives: Auditory Brain Stem Response (ABR is a result of eight nerve and brain stem nuclei stimulation. Several factors may affect the latencies, interpeak latencies and amplitudes in ABR especially sex and age. In this study, age and sex influence on ABR were studied. Methods: This study was performed on 120 cases (60 males and 60 females at Akhavan rehabilitation center of university of welfare and rehabilitation sciences, Tehran, Iran. Cases were divided in three age groups: 18-30, 31-50 and 51-70 years old. Each age group consists of 20 males and 20 females. Age and sex influences on absolute latency of wave I and V, and IPL of I-V were examined. Results: Independent t test showed that females have significantly shorter latency of wave I, V, and IPL I-V latency (P<0.001 than males. Two way ANOVA showed that latency of wave I, V and IPL I-V in 51-70 years old group was significantly higher than 18-30 and 31-50 years old groups (P<0.001 Discussion: According to the results of present study and similar studies, in clinical practice, different norms for older adults and both genders should be established.

  19. Prevalence of brain atrophy in dogs submitted to cranial tomography in FMVZ - UNESP Botucatu: retrospective study; Prevalencia de atrofia cerebral em caes submetidos a tomografia craniana na FMVZ - UNESP Botucatu: estudo retrospectivo

    Energy Technology Data Exchange (ETDEWEB)

    Babicsak, Viviam Rocco; Belotta, Alexandra Frey; Oliveira, Hugo Salvador de; Zardo, Karen Maciel; Santos, Debora Rodrigues dos; Mamprim, Maria Jaqueline; Machado, Vania Maria de Vasconcelos; Vulcano, Luiz Carlos, E-mail: viviam.babicsak@gmail.com [Universidade Estadual Paulista Julio de Mesquita Filho (FMVZ/UNESP), Botucatu, SP (Brazil). Faculdade de Medicina Veterinaria e Zootecnia . Dept. de Reproducao Animal e Radiologia Veterinaria

    2012-07-01

    Brain atrophy is diagnosed by imaging methods that allow the verification of the widening of cerebral sulci and ventricular dilatation. In this retrospective study, in which the cranial CT scans of 150 dogs were evaluated, brain atrophy was identified in 16 animals. Mixed breed dogs were the most affected, followed by poodles, maltese, dachshunds, yorkshires, pinschers and cockers. Brain atrophy was observed in animals of all age groups, being more prevalent in middle aged dogs followed by elderly animals, in which this alteration can be commonly found. The identification of reduced brain volume, however, may not be the cause of neurological signs expressed by animals since in some dogs of this study it was considered a finding. (author)

  20. A case of a brain stem abscess with a favorable outcome

    NARCIS (Netherlands)

    Bulthuis, Vincent J; Gubler, Felix S; Teernstra, Onno P M; Temel, Yasin

    2015-01-01

    BACKGROUND: A brain stem abscess is a rare and severe medical condition. Here, we present a rare case of a brain stem abscess in a young pregnant woman, requiring acute stereotactic intervention. CASE DESCRIPTION: A 36-year-old woman presented with a headache, nausea, and vomiting, and computed

  1. A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA

    Directory of Open Access Journals (Sweden)

    Andrea Luchetti

    2015-08-01

    Full Text Available Spinal muscular atrophy (SMA is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1, encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs, leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.

  2. Progressive multifocal leukoencephalopathy limited to the brain stem

    Energy Technology Data Exchange (ETDEWEB)

    Kastrup, O.; Maschke, M.; Diener, H.C. [Neurologische Universitaetsklinik, University of Essen (Germany); Wanke, I. [Department of Neuroradiology, University of Essen (Germany)

    2002-03-01

    Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating slow-virus encephalitis caused by the JC polyomavirus in 2-5% of patients with AIDS. MRI typically shows multiple lesions in the cerebral hemispheres. We present a rare case of rapidly evolving and lethal PML with a severe bulbar syndrome and spastic tetraparesis in a patient with AIDS. MRI showed high-signal lesions on T2-weighted images confined to the brain stem, extending from the medulla oblongata to the midbrain. JC virus polymerase chain reaction in cerebrospinal fluid was positive, and neuropathology showed the findings of PML. This case was also notable because of the rapid progression despite improved immune status with antiretroviral therapy. (orig.)

  3. Proliferation of differentiated glial cells in the brain stem

    Directory of Open Access Journals (Sweden)

    Barradas P.C.

    1998-01-01

    Full Text Available Classical studies of macroglial proliferation in muride rodents have provided conflicting evidence concerning the proliferating capabilities of oligodendrocytes and microglia. Furthermore, little information has been obtained in other mammalian orders and very little is known about glial cell proliferation and differentiation in the subclass Metatheria although valuable knowledge may be obtained from the protracted period of central nervous system maturation in these forms. Thus, we have studied the proliferative capacity of phenotypically identified brain stem oligodendrocytes by tritiated thymidine radioautography and have compared it with known features of oligodendroglial differentiation as well as with proliferation of microglia in the opossum Didelphis marsupialis. We have detected a previously undescribed ephemeral, regionally heterogeneous proliferation of oligodendrocytes expressing the actin-binding, ensheathment-related protein 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase, that is not necessarily related to the known regional and temporal heterogeneity of expression of CNPase in cell bodies. On the other hand, proliferation of microglia tagged by the binding of Griffonia simplicifolia B4 isolectin, which recognizes an alpha-D-galactosyl-bearing glycoprotein of the plasma membrane of macrophages/microglia, is known to be long lasting, showing no regional heterogeneity and being found amongst both ameboid and differentiated ramified cells, although at different rates. The functional significance of the proliferative behavior of these differentiated cells is unknown but may provide a low-grade cell renewal in the normal brain and may be augmented under pathological conditions.

  4. Dominant optic atrophy

    DEFF Research Database (Denmark)

    Lenaers, Guy; Hamel, Christian; Delettre, Cécile

    2012-01-01

    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....

  5. Multiple System Atrophy

    Science.gov (United States)

    ... Home » Disorders » Patient & Caregiver Education » Fact Sheets Multiple System Atrophy Fact Sheet What is multiple system atrophy? ... can I get more information? What is multiple system atrophy? Multiple system atrophy (MSA) is a progressive ...

  6. Breaking the Blood-Brain Barrier With Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain.

    Science.gov (United States)

    Tajiri, Naoki; Lee, Jea Young; Acosta, Sandra; Sanberg, Paul R; Borlongan, Cesar V

    2016-01-01

    Blood-brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague-Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke.

  7. Auditory Brain Stem Processing in Reptiles and Amphibians: Roles of Coupled Ears

    DEFF Research Database (Denmark)

    Willis, Katie L.; Christensen-Dalsgaard, Jakob; Carr, Catherine

    2014-01-01

    Comparative approaches to the auditory system have yielded great insight into the evolution of sound localization circuits, particularly within the nonmammalian tetrapods. The fossil record demonstrates multiple appearances of tympanic hearing, and examination of the auditory brain stem of variou...

  8. Wallerian degeneration of the corticospinal tract in the brain stem; MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Akira; Onomura, Kentaro; Ohno, Masato (Kyushu Rosai Hospital, Kitakyushu, Fukuoka (Japan))

    1989-04-01

    Magnetic resonance imaging (MRI) of wallerian degeneration of the corticospinal tract in the brain stem was studied in 25 patients with chronic supratentorial vascular accidents. In the relatively early stages, at least three months after ictus, increased signal intensities in axial T{sub 2}-weighted images - with or without decreased signal intensities in axial T{sub 1}-weighted images - were observed in the brain stem ipsilaterally. In later stages, at least six months after ictus, shrinkage of the brain stem ipsilaterally - with or without decreased signal intensities - was clearly observed in axial T{sub 1}-weighted images. MRI is therefore regarded a sensitive diagnostic modality for evaluating wallerian degeneration in the brain stem. (author).

  9. Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression.

    Science.gov (United States)

    Behnan, Jinan; Isakson, Pauline; Joel, Mrinal; Cilio, Corrado; Langmoen, Iver A; Vik-Mo, Einar O; Badn, Wiaam

    2014-05-01

    The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These brain tumor-derived mesenchymal stem cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/-) and have multipotent differentiation capacity. We show that the infiltration of BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the proliferation rate of GL261 cells in vitro. For the first time, we report that the majority of GL261 cells expressed mesenchymal phenotype under both adherent and sphere culture conditions in vitro and that the non-MSC population is nontumorigenic in vivo. Although the GL261 cell line expressed mesenchymal phenotype markers in vitro, most BT-MSCs are recruited cells from host origin in both wild-type GL261 inoculated into green fluorescent protein (GFP)-transgenic mice and GL261-GFP cells inoculated into wild-type mice. We show the expression of chemokine receptors CXCR4 and CXCR6 on different recruited cell populations. In vivo, the GL261 cells change marker profile and acquire a phenotype that is more similar to cells growing in sphere culture conditions. Finally, we identify a BT-MSC population in human glioblastoma that is CD44+CD9+CD166+ both in freshly isolated and culture-expanded cells. Our data indicate that cells with MSC-like phenotype infiltrate into the tumor stroma and play an important role in tumor cell growth in vitro and in vivo. Thus, we suggest that targeting BT-MSCs could be a possible strategy for treating glioblastoma patients. © 2013 AlphaMed Press.

  10. Childhood Brain Stem Glioma Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Childhood brain stem glioma presents as a diffuse intrinsic pontine glioma (DIPG; a fast-growing tumor that is difficult to treat and has a poor prognosis) or a focal glioma (grows more slowly, is easier to treat, and has a better prognosis). Learn about the diagnosis, cellular classification, staging, treatment, and clinical trials for pediatric brain stem glioma in this expert-reviewed summary.

  11. Clinical case of dentato-rubro-pallido-luysian atrophy (DRPLA)

    Energy Technology Data Exchange (ETDEWEB)

    Katsube, Tomoko; Kobayashi, Shotai; Yamaguchi, Shuhei; Tsunematsu, Tokugoro; Shimada, Yasuo

    1987-06-01

    Dentato-rubro-pallido-luysian atrophy (DRPLA) has been described as an atypical type of spino-cerebellar degeneration by J.K. Smith (1958). Choreo-athetoid movement characterizes the DRPLA. We here report a case of DRPLA that was suspected from clinical symptoms and CT brain examinations. Case report: A 36-year-old man was admitted to the hospital because of involuntary movements of the extremities in July, 1978. He had epileptic seizures since the age of 25. Since then, his intelligence had gradually been getting worse. At the same time, dysarthria (slow and slurred speech) also appeared. The neurological examination on admission revealed choreo-athetoid movements, with ataxia of the extremities, trancal ataxia, ataxic speech, moderate dementia, and a disturbance of the smooth-pursuit eye movements. He could not maintain his eye position in a steady gaze, but nystagmus was absent. A brain CT scan revealed a marked atrophy of the upper brain stem and cerebellar peduncle. The cerebral atrophy was mild, and caudate nuclei were spared. The electroencephalograph showed a slow, diffuse, high-voltage wave, with an associated spike and waves. The cerebrospinal fluid examination was normal. An electrophysiological examination revealed no myoclonus in the extremities. These clinical findings suggested that this case is a pseudo-Huntington form of DRPLA.

  12. Targeted delivery of neural stem cells to the brain using MRI-guided focused ultrasound to disrupt the blood-brain barrier.

    Directory of Open Access Journals (Sweden)

    Alison Burgess

    Full Text Available Stem cell therapy is a promising strategy to treat neurodegenerative diseases, traumatic brain injury, and stroke. For stem cells to progress towards clinical use, the risks associated with invasive intracranial surgery used to deliver the cells to the brain, needs to be reduced. Here, we show that MRI-guided focused ultrasound (MRIgFUS is a novel method for non-invasive delivery of stem cells from the blood to the brain by opening the blood brain barrier (BBB in specific brain regions. We used MRI guidance to target the ultrasound beam thereby delivering the iron-labeled, green fluorescent protein (GFP-expressing neural stem cells specifically to the striatum and the hippocampus of the rat brain. Detection of cellular iron using MRI established that the cells crossed the BBB to enter the brain. After sacrifice, 24 hours later, immunohistochemical analysis confirmed the presence of GFP-positive cells in the targeted brain regions. We determined that the neural stem cells expressed common stem cell markers (nestin and polysialic acid suggesting they survived after transplantation with MRIgFUS. Furthermore, delivered stem cells expressed doublecortin in vivo indicating the stem cells were capable of differentiating into neurons. Together, we demonstrate that transient opening of the BBB with MRIgFUS is sufficient for transplantation of stem cells from the blood to targeted brain structures. These results suggest that MRIgFUS may be an effective alternative to invasive intracranial surgery for stem cell transplantation.

  13. The BRAIN Initiative Provides a Unifying Context for Integrating Core STEM Competencies into a Neurobiology Course.

    Science.gov (United States)

    Schaefer, Jennifer E

    2016-01-01

    The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative introduced by the Obama Administration in 2013 presents a context for integrating many STEM competencies into undergraduate neuroscience coursework. The BRAIN Initiative core principles overlap with core STEM competencies identified by the AAAS Vision and Change report and other entities. This neurobiology course utilizes the BRAIN Initiative to serve as the unifying theme that facilitates a primary emphasis on student competencies such as scientific process, scientific communication, and societal relevance while teaching foundational neurobiological content such as brain anatomy, cellular neurophysiology, and activity modulation. Student feedback indicates that the BRAIN Initiative is an engaging and instructional context for this course. Course module organization, suitable BRAIN Initiative commentary literature, sample primary literature, and important assignments are presented.

  14. Microcephaly-lymphedema-chorioretinal dysplasia associated with pachymicrogyria and atrophy of the cerebellar vermis: an integration of brain-ocular migration disorders.

    Science.gov (United States)

    Pastora, Natalia; Peralta, Jesus; Canal-Fontcuberta, Irene; Grabowska, Anna; Pulido, Jose S; Abelairas, Jose; Armada, Felix; Garcia-Alix, Alfredo

    2012-06-01

    Microcephaly-lymphedema-chorioretinal dysplasia (OMIM 152950) is a rare malformative inherited disorder that can be associated with other systemic features. Other ocular and brain anomalies rather than microcephaly and chorioretinal dysplasia have been inconstantly reported in this syndrome. We present a case of microcephaly-lymphedema-chorioretinal dysplasia with a dysmorphic facies, hypertonicity in the extremities and neuropsychomotor delay. Ophthalmological examination revealed bilateral nystagmus, microphthalmia, posterior subcapsular cataratacts, extensive chorioretinal dysplasia, optic nerve aplasia, persistent fetal vasculature, and absent retinal vessels. Magnetic resonance revealed pachymicrogyria and discrete atrophy of vermis cerebelosum and confirmed optic nerve hypoplasia. The developmental alterations observed in the retina of this patient could be analogous to central nervous system anomalies, reflecting a reduction in neural population. Ophthalmic examination of children with microcephaly is warranted.

  15. The Future Vocation of Neural Stem Cells: Lineage Commitment in Brain Development and Evolution.

    Science.gov (United States)

    Nomura, Tadashi; Gotoh, Hitoshi; Ono, Katsuhiko

    2017-08-24

    Understanding the fate commitment of neural stem cells is critical to identify the regulatory mechanisms in developing brains. Genetic lineage-tracing has provided a powerful strategy to unveil the heterogeneous nature of stem cells and their descendants. However, recent studies have reported controversial data regarding the heterogeneity of neural stem cells in the developing mouse neocortex, which prevents a decisive conclusion on this issue. Here, we review the progress that has been made using lineage-tracing analyses of the developing neocortex and discuss stem cell heterogeneity from the viewpoint of comparative and evolutionary biology.

  16. STEM Tones Pre-Activate Suffixes in the Brain

    Science.gov (United States)

    Söderström, Pelle; Horne, Merle; Roll, Mikael

    2017-01-01

    Results from the present event-related potentials (ERP) study show that tones on Swedish word stems can rapidly pre-activate upcoming suffixes, even when the word stem does not carry any lexical meaning. Results also show that listeners are able to rapidly restore suffixes which are replaced with a cough. Accuracy in restoring suffixes correlated…

  17. Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study.

    Science.gov (United States)

    Santamaria, Xavier; Cabanillas, Sergio; Cervelló, Irene; Arbona, Cristina; Raga, Francisco; Ferro, Jaime; Palmero, Julio; Remohí, Jose; Pellicer, Antonio; Simón, Carlos

    2016-05-01

    Could cell therapy using autologous peripheral blood CD133+ bone marrow-derived stem cells (BMDSCs) offer a safe and efficient therapeutic approach for patients with refractory Asherman's syndrome (AS) and/or endometrial atrophy (EA) and a wish to conceive? In the first 3 months, autologous cell therapy, using CD133+ BMDSCs in conjunction with hormonal replacement therapy, increased the volume and duration of menses as well as the thickness and angiogenesis processes of the endometrium while decreasing intrauterine adhesion scores. AS is characterized by the presence of intrauterine adhesions and EA prevents the endometrium from growing thicker than 5 mm, resulting in menstruation disorders and infertility. Many therapies have been attempted for these conditions, but none have proved effective. This was a prospective, experimental, non-controlled study. There were 18 patients aged 30-45 years with refractory AS or EA were recruited, and 16 of these completed the study. Medical history, physical examination, endometrial thickness, intrauterine adhesion score and neoangiogenesis were assessed before and 3 and 6 months after cell therapy. After the initial hysteroscopic diagnosis, BMDSC mobilization was performed by granulocyte-CSF injection, then CD133+ cells were isolated through peripheral blood aphaeresis to obtain a mean of 124.39 million cells (range 42-236), which were immediately delivered into the spiral arterioles by catheterization. Subsequently, endometrial treatment after stem cell therapy was assessed in terms of restoration of menses, endometrial thickness (by vaginal ultrasound), adhesion score (by hysteroscopy), neoangiogenesis and ongoing pregnancy rate. The study was conducted at Hospital Clínico Universitario of Valencia and IVI Valencia (Spain). All 11 AS patients exhibited an improved uterine cavity 2 months after stem cell therapy. Endometrial thickness increased from an average of 4.3 mm (range 2.7-5) to 6.7 mm (range 3.1-12) ( ITALIC! P = 0

  18. Adult human dental pulp stem cells promote blood-brain barrier permeability through vascular endothelial growth factor-a expression.

    Science.gov (United States)

    Winderlich, Joshua N; Kremer, Karlea L; Koblar, Simon A

    2016-06-01

    Stem cell therapy is a promising new treatment option for stroke. Intravascular administration of stem cells is a valid approach as stem cells have been shown to transmigrate the blood-brain barrier. The mechanism that causes this effect has not yet been elucidated. We hypothesized that stem cells would mediate localized discontinuities in the blood-brain barrier, which would allow passage into the brain parenchyma. Here, we demonstrate that adult human dental pulp stem cells express a soluble factor that increases permeability across an in vitro model of the blood-brain barrier. This effect was shown to be the result of vascular endothelial growth factor-a. The effect could be amplified by exposing dental pulp stem cell to stromal-derived factor 1, which stimulates vascular endothelial growth factor-a expression. These findings support the use of dental pulp stem cell in therapy for stroke. © The Author(s) 2015.

  19. [Stem Cells in the Brain of Mammals and Human: Fundamental and Applied Aspects].

    Science.gov (United States)

    Aleksandrova, M A; Marey, M V

    2015-01-01

    Brain stem cells represent an extremely intriguing phenomenon. The aim of our review is to present an integrity vision of their role in the brain of mammals and humans, and their clinical perspectives. Over last two decades, investigations of biology of the neural stem cells produced significant changes in general knowledge about the processes of development and functioning of the brain. Researches on the cellular and molecular mechanisms of NSC differentiation and behavior led to new understanding of their involvement in learning and memory. In the regenerative medicine, original therapeutic approaches to neurodegenerative brain diseases have been elaborated due to fundamental achievements in this field. They are based on specific regenerative potential of neural stem cells and progenitor cells, which possess the ability to replace dead cells and express crucially significant biologically active factors that are missing in the pathological brain. For the needs of cell substitution therapy in the neural diseases, adequate methods of maintaining stem cells in culture and their differentiation into different types of neurons and glial cells, have been developed currently. The success of modern cellular technologies has significantly expanded the range of cells used for cell therapy. The near future may bring new perspective and distinct progress in brain cell therapy due to optimizing the cells types most promising for medical needs.

  20. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells.

    Science.gov (United States)

    Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi; Shah, Khalid

    2015-06-01

    Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications. © The Author (2015). Published by Oxford University Press on

  1. Sumoylation of hypoxia-inducible factor-1α ameliorates failure of brain stem cardiovascular regulation in experimental brain death.

    Directory of Open Access Journals (Sweden)

    Julie Y H Chan

    2011-03-01

    Full Text Available One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of brain death resides in the rostral ventrolateral medulla (RVLM. RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1α (HIF-1α plays a pro-life role in experimental brain death, and HIF-1α is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1α in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death.A clinically relevant animal model that employed mevinphos as the experimental insult in Sprague-Dawley rat was used. Biochemical changes in RVLM during distinct phenotypes in systemic arterial pressure spectrum that reflect maintained or defunct brain stem cardiovascular regulation were studied. Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1, Ubc9 (the only known conjugating enzyme for the sumoylation pathway or HIF-1α, augmented sumoylation of HIF-1α, nucleus-bound translocation and enhanced transcriptional activity of HIF-1α in RVLM neurons took place preferentially during the pro-life phase of experimental brain death. Furthermore, loss-of-function manipulations by immunoneutralization of SUMO-1, Ubc9 or HIF-1α in RVLM blunted the upregulated nitric oxide synthase I/protein kinase G signaling cascade, which sustains the brain stem cardiovascular regulatory machinery during the pro-life phase.We conclude that sumoylation of HIF-1α in RVLM ameliorates brain stem

  2. Patient-derived stem cells: pathways to drug discovery for brain diseases

    Directory of Open Access Journals (Sweden)

    Alan eMackay-Sim

    2013-03-01

    Full Text Available The concept of drug discovery through stem cell biology is based on technological developments whose genesis is now coincident. The first is automated cell microscopy with concurrent advances in image acquisition and analysis, known as high content screening (HCS. The second is patient-derived stem cells for modelling the cell biology of brain diseases. HCS has developed from the requirements of the pharmaceutical industry for high throughput assays to screen thousands of chemical compounds in the search for new drugs. HCS combines new fluorescent probes with automated microscopy and computational power to quantify the effects of compounds on cell functions. Stem cell biology has advanced greatly since the discovery of genetic reprogramming of somatic cells into induced pluripotent stem cells (iPSCs. There is now a rush of papers describing their generation from patients with various diseases of the nervous system. Although the majority of these have been genetic diseases, iPSCs have been generated from patients with complex diseases (schizophrenia and sporadic Parkinson’s disease. Some genetic diseases are also modelled in embryonic stem cells generated from blastocysts rejected during in vitro fertilisation. Neural stem cells have been isolated from post-mortem brain of Alzheimer’s patients and neural stem cells generated from biopsies of the olfactory organ of patients is another approach. These olfactory neurosphere-derived cells demonstrate robust disease-specific phenotypes in patients with schizophrenia and Parkinson’s disease. High content screening is already in use to find small molecules for the generation and differentiation of embryonic stem cells and induced pluripotent stem cells. The challenges for using stem cells for drug discovery are to develop robust stem cell culture methods that meet the rigorous requirements for repeatable, consistent quantities of defined cell types at the industrial scale necessary for high

  3. Control of abdominal muscles by brain stem respiratory neurons in the cat

    Science.gov (United States)

    Miller, Alan D.; Ezure, Kazuhisa; Suzuki, Ichiro

    1985-01-01

    The nature of the control of abdominal muscles by the brain stem respiratory neurons was investigated in decerebrate unanesthetized cats. First, it was determined which of the brain stem respiratory neurons project to the lumbar cord (from which the abdominal muscles receive part of their innervation), by stimulating the neurons monopolarly. In a second part of the study, it was determined if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons; in these experiments, discriminate spontaneous spikes of antidromically acivated expiratory (E) neurons were used to trigger activity from both L1 and L2 nerves. A large projection was observed from E neurons in the caudal ventral respiratory group to the contralateral upper lumber cord. However, cross-correlation experiments found only two (out of 47 neuron pairs tested) strong monosynaptic connections between brain stem neurons and abdominal motoneurons.

  4. Using multiple imputation to efficiently correct cerebral MRI whole brain lesion and atrophy data in patients with multiple sclerosis.

    Science.gov (United States)

    Chua, Alicia S; Egorova, Svetlana; Anderson, Mark C; Polgar-Turcsanyi, Mariann; Chitnis, Tanuja; Weiner, Howard L; Guttmann, Charles R G; Bakshi, Rohit; Healy, Brian C

    2015-10-01

    Automated segmentation of brain MRI scans into tissue classes is commonly used for the assessment of multiple sclerosis (MS). However, manual correction of the resulting brain tissue label maps by an expert reader remains necessary in many cases. Since automated segmentation data awaiting manual correction are "missing", we proposed to use multiple imputation (MI) to fill-in the missing manually-corrected MRI data for measures of normalized whole brain volume (brain parenchymal fraction-BPF) and T2 hyperintense lesion volume (T2LV). Automated and manually corrected MRI measures from 1300 patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB) were identified. Simulation studies were conducted to assess the performance of MI with missing data both missing completely at random and missing at random. An imputation model including the concurrent automated data as well as clinical and demographic variables explained a high proportion of the variance in the manually corrected BPF (R(2)=0.97) and T2LV (R(2)=0.89), demonstrating the potential to accurately impute the missing data. Further, our results demonstrate that MI allows for the accurate estimation of group differences with little to no bias and with similar precision compared to an analysis with no missing data. We believe that our findings provide important insights for efficient correction of automated MRI measures to obviate the need to perform manual correction on all cases. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Olivopontocerebellar Atrophy

    Science.gov (United States)

    ... Page Diabetic Neuropathy Information Page Dysgraphia Information Page Dyslexia Information Page Dystonias Information Page Empty Sella Syndrome ... Spotlight Find NINDS Clinical Trials Patient & Caregiver Education Fact Sheets Hope Through Research Know Your Brain Preventing ...

  6. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.

    Directory of Open Access Journals (Sweden)

    Ninette Amariglio

    2009-02-01

    Full Text Available BACKGROUND: Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells. METHODS AND FINDINGS: A boy with ataxia telangiectasia (AT was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors. CONCLUSIONS: This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

  7. Comparative Brain Stem Lesions on MRI of Acute Disseminated Encephalomyelitis, Neuromyelitis Optica, and Multiple Sclerosis

    Science.gov (United States)

    Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

    2011-01-01

    Background Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). Objectives To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Methods Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Results Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Conclusions Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases. PMID:21853047

  8. Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Zhengqi Lu

    Full Text Available BACKGROUND: Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM, neuromyelitis optica (NMO, and multiple sclerosis (MS. OBJECTIVES: To investigate comparative brain stem lesions on magnetic resonance imaging (MRI among adult patients with ADEM, NMO, and MS. METHODS: Sixty-five adult patients with ADEM (n = 17, NMO (n = 23, and MS (n = 25 who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. RESULTS: Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001 and MS (94.1% vs. 40.0%, P<0.001; patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001 and ADEM (34.8% vs. 70.6%, P = 0.025; and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001 and MS (91.3% vs. 36.0%, P<0.001. On the axial section of the brain stem, the majority (82.4% of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%; and lesions in patients with MS were found in both the ventral (44.0% and dorsal (56.0% parts. The lesions in patients with ADEM (100% and NMO (91.3% had poorly defined margins, while lesions of patients with MS (76.0% had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%, while lesions in patients with NMO (87.0% and MS (92.0% were asymmetrical or unilateral. CONCLUSIONS: Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.

  9. Stem Tones Pre-activate Suffixes in the Brain.

    Science.gov (United States)

    Söderström, Pelle; Horne, Merle; Roll, Mikael

    2017-04-01

    Results from the present event-related potentials (ERP) study show that tones on Swedish word stems can rapidly pre-activate upcoming suffixes, even when the word stem does not carry any lexical meaning. Results also show that listeners are able to rapidly restore suffixes which are replaced with a cough. Accuracy in restoring suffixes correlated positively with the amplitude of an anterior negative ERP elicited by stem tones. This effect is proposed to reflect suffix pre-activation. Suffixes that were cued by an incorrect tone elicited a left-anterior negativity and a P600, suggesting that the correct processing of the suffix is crucially tied to the activation of the preceding validly associated tone.

  10. Physics strategies for sparing neural stem cells during whole-brain radiation treatments.

    Science.gov (United States)

    Kirby, Neil; Chuang, Cynthia; Pouliot, Jean; Hwang, Andrew; Barani, Igor J

    2011-10-01

    Currently, there are no successful long-term treatments or preventive strategies for radiation-induced cognitive impairments, and only a few possibilities have been suggested. One such approach involves reducing the dose to neural stem cell compartments (within and outside of the hippocampus) during whole-brain radiation treatments for brain metastases. This study investigates the fundamental physics issues associated with the sparing of neural stem cells during photon radiotherapy for brain metastases. Several factors influence the stem cell dose: intracranial scattering, collimator leakage, beam energy, and total number of beams. The relative importance of these factors is investigated through a set of radiation therapy plans, which are all variations of an initial 6 MV intensity-modulated radiation therapy (IMRT) plan designed to simultaneously deliver a whole-brain dose of 30 Gy and maximally reduce stem cell compartment dose. Additionally, an in-house leaf segmentation algorithm was developed that utilizes jaw motion to minimize the collimator leakage. The plans are all normalized such that 50% of the PTV receives 30 Gy. For the initial 6 MV IMRT plan, 50% of the stem cells receive a dose greater than 6.3 Gy. Calculations indicate that 3.6 Gy of this dose originates from intracranial scattering. The jaw-tracking segmentation algorithm, used in conjunction with direct machine parameter optimization, reduces the 50% stem cell dose to 4.3 and 3.7 Gy for 6 and 10 MV treatment beams, respectively. Intracranial scattering alone is responsible for a large dose contribution to the stem cell compartment. It is, therefore, important to minimize other contributing factors, particularly the collimator leakage, to maximally reduce dose to these critical structures. The use of collimator jaw tracking in conjunction with modern collimators can minimize this leakage.

  11. Physics strategies for sparing neural stem cells during whole-brain radiation treatments

    Energy Technology Data Exchange (ETDEWEB)

    Kirby, Neil; Chuang, Cynthia; Pouliot, Jean; Hwang, Andrew; Barani, Igor J. [Department of Radiation Oncology, University of California San Francisco, San Francisco, California 94143-1708 (United States)

    2011-10-15

    Purpose: Currently, there are no successful long-term treatments or preventive strategies for radiation-induced cognitive impairments, and only a few possibilities have been suggested. One such approach involves reducing the dose to neural stem cell compartments (within and outside of the hippocampus) during whole-brain radiation treatments for brain metastases. This study investigates the fundamental physics issues associated with the sparing of neural stem cells during photon radiotherapy for brain metastases. Methods: Several factors influence the stem cell dose: intracranial scattering, collimator leakage, beam energy, and total number of beams. The relative importance of these factors is investigated through a set of radiation therapy plans, which are all variations of an initial 6 MV intensity-modulated radiation therapy (IMRT) plan designed to simultaneously deliver a whole-brain dose of 30 Gy and maximally reduce stem cell compartment dose. Additionally, an in-house leaf segmentation algorithm was developed that utilizes jaw motion to minimize the collimator leakage. Results: The plans are all normalized such that 50% of the PTV receives 30 Gy. For the initial 6 MV IMRT plan, 50% of the stem cells receive a dose greater than 6.3 Gy. Calculations indicate that 3.6 Gy of this dose originates from intracranial scattering. The jaw-tracking segmentation algorithm, used in conjunction with direct machine parameter optimization, reduces the 50% stem cell dose to 4.3 and 3.7 Gy for 6 and 10 MV treatment beams, respectively. Conclusions: Intracranial scattering alone is responsible for a large dose contribution to the stem cell compartment. It is, therefore, important to minimize other contributing factors, particularly the collimator leakage, to maximally reduce dose to these critical structures. The use of collimator jaw tracking in conjunction with modern collimators can minimize this leakage.

  12. No evidence for an effect on brain atrophy rate of atorvastatin add-on to interferon β1b therapy in relapsing-remitting multiple sclerosis (the ARIANNA study).

    Science.gov (United States)

    Lanzillo, Roberta; Quarantelli, Mario; Pozzilli, Carlo; Trojano, Maria; Amato, Maria Pia; Marrosu, Maria G; Francia, Ada; Florio, Ciro; Orefice, Giuseppe; Tedeschi, Gioacchino; Bellantonio, Paolo; Annunziata, Pasquale; Grimaldi, Luigi M; Comerci, Marco; Brunetti, Arturo; Bonavita, Vincenzo; Alfano, Bruno; Marini, Stefano; Brescia Morra, Vincenzo

    2016-08-01

    A previous phase 2 trial has suggested that statins might delay brain atrophy in secondary progressive multiple sclerosis. The objective of this study was to evaluate the effect of atorvastatin add-on therapy on cerebral atrophy in relapsing-remitting multiple sclerosis. This randomised, placebo-controlled study compared atorvastatin 40 mg or placebo add-on therapy to interferon β1b for 24 months. Brain magnetic resonance imaging, multiple sclerosis functional composite score, Rao neuropsychological battery and expanded disability status scale were evaluated over 24 months. A total of 154 patients were randomly assigned, 75 in the atorvastatin and 79 in the placebo arms, with a comparable drop-out rate (overall 23.4%). Brain atrophy over 2 years was not different in the two arms (-0.38% and -0.32% for the atorvastatin and placebo groups, respectively). Relapse rate, expanded disability status scale, multiple sclerosis functional composite score or cognitive changes were not different in the two arms. Patients withdrawing from the study had a higher number of relapses in the previous 2 years (P=0.04) and a greater probability of relapsing within 12 months. Our results suggest that the combination of atorvastatin and interferon β1b is not justified in early relapsing-remitting multiple sclerosis and adds to the body of evidence indicating an absence of significant radiological and clinical benefit of statins in relapsing-remitting multiple sclerosis. © The Author(s), 2015.

  13. Syrinx of the Spinal Cord and Brain Stem

    Science.gov (United States)

    ... imaging (MRI) of the entire spinal cord and brain is done after paramagnetic contrast agent, such as ... neurosurgeon may make a hole in a syrinx to drain it and prevent it from expanding, but surgery ...

  14. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  15. Cerebral transplantation of encapsulated mesenchymal stem cells improves cellular pathology after experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Heile, Anna M B; Wallrapp, Christine; Klinge, Petra M

    2009-01-01

    PURPOSE: "Naked" human mesenchymal stem cells (MSC) are neuro-protective in experimental brain injury (TBI). In a controlled cortical impact (CCI) rat model, we investigated whether encapsulated MSC (eMSC) act similarly, and whether efficacy is augmented using cells transfected to produce the neuro...

  16. Role of astrocytes as neural stem cells in the adult brain

    Science.gov (United States)

    Gonzalez-Perez, Oscar; Quiñones-Hinojosa, Alfredo

    2012-01-01

    In the adult mammalian brain, bona fide neural stem cells were discovered in the subventricular zone (SVZ), the largest neurogenic niche lining the striatal wall of the lateral ventricles of the brain. In this region resides a subpopulation of astrocytes that express the glial fibrillary acidic protein (GFAP), nestin and LeX. Astonishingly, these GFAP-expressing progenitors display stem-cell-like features both in vivo and in vitro. Throughout life SVZ astrocytes give rise to interneurons and oligodendrocyte precursors, which populate the olfactory bulb and the white matter, respectively. The role of the progenies of SVZ astrocytes has not been fully elucidated, but some evidence indicates that the new neurons play a role in olfactory discrimination, whereas oligodendrocytes contribute to myelinate white matter tracts. In this chapter, we describe the astrocytic nature of adult neural stem cells, their organization into the SVZ and some of their molecular and genetic characteristics. PMID:23619383

  17. Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell Grafts in the Ischemic Mouse Brain.

    Science.gov (United States)

    Green, Claudia; Minassian, Anuka; Vogel, Stefanie; Diedenhofen, Michael; Beyrau, Andreas; Wiedermann, Dirk; Hoehn, Mathias

    2018-02-14

    Past investigations on stem cell-mediated recovery after stroke have limited their focus on the extent and morphological development of the ischemic lesion itself over time or on the integration capacity of the stem cell graft ex vivo However, an assessment of the long-term functional and structural improvement in vivo is essential to reliably quantify the regenerative capacity of cell implantation after stroke. We induced ischemic stroke in nude mice and implanted human neural stem cells (H9 derived) into the ipsilateral cortex in the acute phase. Functional and structural connectivity changes of the sensorimotor network were noninvasively monitored using magnetic resonance imaging for 3 months after stem cell implantation. A sharp decrease of the functional sensorimotor network extended even to the contralateral hemisphere, persisting for the whole 12 weeks of observation. In mice with stem cell implantation, functional networks were stabilized early on, pointing to a paracrine effect as an early supportive mechanism of the graft. This stabilization required the persistent vitality of the stem cells, monitored by bioluminescence imaging. Thus, we also observed deterioration of the early network stabilization upon vitality loss of the graft after a few weeks. Structural connectivity analysis showed fiber-density increases between the cortex and white matter regions occurring predominantly on the ischemic hemisphere. These fiber-density changes were nearly the same for both study groups. This motivated us to hypothesize that the stem cells can influence, via early paracrine effect, the functional networks, while observed structural changes are mainly stimulated by the ischemic event. SIGNIFICANCE STATEMENT In recent years, research on strokes has made a shift away from a focus on immediate ischemic effects and towards an emphasis on the long-range effects of the lesion on the whole brain. Outcome improvements in stem cell therapies also require the understanding of

  18. Breath-holding spells may be associated with maturational delay in myelination of brain stem.

    Science.gov (United States)

    Vurucu, Sebahattin; Karaoglu, Abdulbaki; Paksu, Sukru M; Oz, Oguzhan; Yaman, Halil; Gulgun, Mustafa; Babacan, Oguzhan; Unay, Bulent; Akin, Ridvan

    2014-02-01

    To evaluate possible contribution of maturational delay of brain stem in the etiology of breath-holding spells in children using brain stem auditory evoked potentials. The study group included children who experienced breath-holding spells. The control group consisted of healthy age- and sex-matched children. Age, gender, type and frequency of spell, hemoglobin, and ferritin levels in study group and brain stem auditory evoked potentials results in both groups were recorded. Study group was statistically compared with control group for brain stem auditory evoked potentials. The mean age of study and control groups was 26.3 ± 14.6 and 28.9 ± 13.9 months, respectively. The III-V and I-V interpeak latencies were significantly prolonged in the study group compared with the control group (2.07 ± 0.2 milliseconds; 1.92 ± 0.13 milliseconds and 4.00 ± 0.27 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.009 and P = 0.03, respectively). At the same time, III-V and I-V interpeak latencies of patients without anemia in the study group compared with those of control group were significantly prolonged (2.09 ± 0.24 milliseconds; 1.92 ± 0.13 milliseconds and 4.04 ± 0.28 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.007 and P = 0.01, respectively). Our results consider that maturational delay in myelination of brain stem may have a role in the etiology of breath-holding spells in children.

  19. MRI measurements of the brain stem and cerebellum in high functioning autistic children

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Toshiaki; Tayama, Masanobu; Miyazaki, Masahito; Murakawa, Kazuyoshi; Kuroda, Yasuhiro (Tokushima Univ. (Japan). School of Medicine)

    1994-01-01

    To determine involvements of the brain stem and/or cerebellum in autism, we compared midsagittal magnetic resonance images of the brains of high functioning autistic children with those of normal controls. We found that the midbrain and medulla oblongata were significantly smaller in these autistic children than in the control children. The pons area did not differ between the two groups, nor was there any difference in the cerebellar vermis area. The ratio of the brain stem and cerebellum to the posterior fossa area did not differ significantly between the high functioning autistic and the control children. The development of the cerebellar vermis area was delayed in autistic children as compared with that in the control children. Thus, it was suggested that significant anatomical changes in the midbrain and medulla oblongata existed in the autistic children. (author).

  20. Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm.

    Science.gov (United States)

    Rahman, Ruman; Heath, Rachel; Grundy, Richard

    2009-04-01

    Brain tumours are a diverse group of neoplasms that continue to present a formidable challenge in our attempt to achieve curable intervention. Our conceptual framework of human brain cancer has been redrawn in the current decade. There is a gathering acceptance that brain tumour formation is a phenotypic outcome of dysregulated neurogenesis, with tumours viewed as abnormally differentiated neural tissue. In relation, there is accumulating evidence that brain tumours, similar to leukaemia and many solid tumours, are organized as a developmental hierarchy which is maintained by a small fraction of cells endowed with many shared properties of tissue stem cells. Proof that neurogenesis persists throughout adult life, compliments this concept. Although the cancer cell of origin is unclear, the proliferative zones that harbour stem cells in the embryonic, post-natal and adult brain are attractive candidates within which tumour-initiation may ensue. Dysregulated, unlimited proliferation and an ability to bypass senescence are acquired capabilities of cancerous cells. These abilities in part require the establishment of a telomere maintenance mechanism for counteracting the shortening of chromosomal termini. A strategy based upon the synthesis of telomeric repeat sequences by the ribonucleoprotein telomerase, is prevalent in approximately 90% of human tumours studied, including the majority of brain tumours. This review will provide a developmental perspective with respect to normal (neurogenesis) and aberrant (tumourigenesis) cellular turnover, differentiation and function. Within this context our current knowledge of brain tumour telomere/telomerase biology will be discussed with respect to both its developmental and therapeutic relevance to the hierarchical model of brain tumourigenesis presented by the cancer stem cell paradigm.

  1. Brain Tumor Tropism of Transplanted Human Neural Stem Cells Is Induced by Vascular Endothelial Growth Factor

    Directory of Open Access Journals (Sweden)

    Nils Ole Schmidt

    2005-06-01

    Full Text Available The transplantation of neural stem cells (NSCs offers a new potential therapeutic approach as a cell-based delivery system for gene therapy in brain tumors. This is based on the unique capacity of NSCs to migrate throughout the brain and to target invading tumor cells. However, the signals controlling the targeted migration of transplanted NSCs are poorly defined. We analyzed the in vitro and in vivo effects of angiogenic growth factors and protein extracts from surgical specimens of brain tumor patients on NSC migration. Here, we demonstrate that vascular endothelial growth factor (VEGF is able to induce a long-range attraction of transplanted human NSCs from distant sites in the adult brain. Our results indicate that tumorupregulated VEGF and angiogenic-activated microvasculature are relevant guidance signals for NSC tropism toward brain tumors.

  2. Genetic ablation of caveolin-1 increases neural stem cell proliferation in the subventricular zone (SVZ) of the adult mouse brain.

    Science.gov (United States)

    Jasmin, Jean-François; Yang, Ming; Iacovitti, Lorraine; Lisanti, Michael P

    2009-12-01

    Adult neural stem cells are self-renewing multipotent cells that have the potential to replace dysfunctional and/or dying neuronal cells at the site of brain injury or degeneration. Caveolins are well-known tumor-suppressor genes that were recently found to be involved in the regulation of stem cell proliferation. For instance, ablation of the caveolin-1 (Cav-1) gene in mice markedly increases the proliferation of intestinal and mammary stem cells. However, the roles of caveolins in the proliferation of adult neural stem cells still remain unknown. In this study, dual-label immunofluorescence analysis of the proliferation marker, Ki67, and the stem cell markers, nestin and Sox2, was performed on brains of 8 week-old wild-type (WT) and Cav-1 knockout (KO) mice. Our results demonstrate an increased number of Ki67-positive nuclei in the subventricular zone (SVZ) of Cav-1 KO brains. Importantly, our dual-label immunofluorescence analyses demonstrate increased co-localization of Ki67 with both nestin and Sox2 in the SVZ of Cav-1 KO brains. Remarkably similar results were also obtained with Cav-2 and Cav-3 KO mouse brains as well, with increased proliferation of adult neural stem cells. Thus, the SVZ of caveolin KO mouse brains displays an increased proliferation of adult neural stem cells. Caveolin proteins might represent new crucial regulators of adult neural stem cell proliferation.

  3. Does State Merit-Based Aid Stem Brain Drain?

    Science.gov (United States)

    Zhang, Liang; Ness, Erik C.

    2010-01-01

    In this study, the authors use college enrollment and migration data to test the brain drain hypothesis. Their results suggest that state merit scholarship programs do indeed stanch the migration of "best and brightest" students to other states. In the aggregate and on average, the implementation of state merit aid programs increases the…

  4. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    ... 26-70 years) who were operated for brain astrocytomas. Immunohistochemical staining for Nestin, TP53, and Ki 67 was carried out on paraffin embedded tissue samples from the resected gliomas. Scores for markers' expression were statistically correlated with patients' age and gender, tumor grade, and patients' survival ...

  5. Integration and relative value of biomarkers for prediction of MCI to AD progression: Spatial patterns of brain atrophy, cognitive scores, APOE genotype and CSF biomarkers

    Directory of Open Access Journals (Sweden)

    Xiao Da

    2014-01-01

    Full Text Available This study evaluates the individual, as well as relative and joint value of indices obtained from magnetic resonance imaging (MRI patterns of brain atrophy (quantified by the SPARE-AD index, cerebrospinal fluid (CSF biomarkers, APOE genotype, and cognitive performance (ADAS-Cog in progression from mild cognitive impairment (MCI to Alzheimer's disease (AD within a variable follow-up period up to 6 years, using data from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1. SPARE-AD was first established as a highly sensitive and specific MRI-marker of AD vs. cognitively normal (CN subjects (AUC = 0.98. Baseline predictive values of all aforementioned indices were then compared using survival analysis on 381 MCI subjects. SPARE-AD and ADAS-Cog were found to have similar predictive value, and their combination was significantly better than their individual performance. APOE genotype did not significantly improve prediction, although the combination of SPARE-AD, ADAS-Cog and APOE ε4 provided the highest hazard ratio estimates of 17.8 (last vs. first quartile. In a subset of 192 MCI patients who also had CSF biomarkers, the addition of Aβ1–42, t-tau, and p-tau181p to the previous model did not improve predictive value significantly over SPARE-AD and ADAS-Cog combined. Importantly, in amyloid-negative patients with MCI, SPARE-AD had high predictive power of clinical progression. Our findings suggest that SPARE-AD and ADAS-Cog in combination offer the highest predictive power of conversion from MCI to AD, which is improved, albeit not significantly, by APOE genotype. The finding that SPARE-AD in amyloid-negative MCI patients was predictive of clinical progression is not expected under the amyloid hypothesis and merits further investigation.

  6. Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscular hypotonia, and brain abnormalities.

    Science.gov (United States)

    Baasch, Anna-Lena; Hüning, Irina; Gilissen, Christian; Klepper, Joerg; Veltman, Joris A; Gillessen-Kaesbach, Gabriele; Hoischen, Alexander; Lohmann, Katja

    2014-04-01

    Epilepsy is a phenotypically and genetically highly heterogeneous disorder with >200 genes linked to inherited forms of the disease. To identify the underlying genetic cause in a patient with intractable seizures, optic atrophy, severe intellectual disability (ID), brain abnormalities, and muscular hypotonia, we performed exome sequencing in a 5-year-old girl and her unaffected parents. In the patient, we detected a novel, de novo missense mutation in the SCN2A (c.5645G>T; p.R1882L) gene encoding the αII -subunit of the voltage-gated sodium channel Nav 1.2. A literature review revealed 33 different SCN2A mutations in 14 families with benign forms of epilepsy and in 21 cases with severe phenotypes. Although almost all benign mutations were inherited, the majority of severe mutations occurred de novo. Of interest, de novo SCN2A mutations have also been reported in five patients without seizures but with ID (n = 3) and/or autism (n = 3). In the present study, we successfully used exome sequencing to detect a de novo mutation in a genetically heterogeneous disorder with epilepsy and ID. Using this approach, we expand the phenotypic spectrum of SCN2A mutations. Our own and literature data indicate that SCN2A-linked severe phenotypes are more likely to be caused by de novo mutations. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  7. Composite Marker of Cognitive Dysfunction and Brain Atrophy is Highly Accurate in Discriminating Between Relapsing-Remitting and Secondary Progressive Multiple Sclerosis.

    Science.gov (United States)

    Kizlaitienė, Rasa; Kaubrys, Gintaras; Giedraitienė, Nataša; Ramanauskas, Naglis; Dementavičienė, Jūratė

    2017-02-01

    BACKGROUND With the advent of numerous new-generation disease-modifying drugs for multiple sclerosis (MS), the discrimination between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) has become a problem of high importance. The aim of our study was to find a simple way to accurately discriminate between RRMS and SPMS that is applicable in clinical practice as a composite marker, using the linear measures of magnetic resonance imaging (MRI) and the results of cognitive tests. MATERIAL AND METHODS We included 88 MS patients in the study: 43 participants had RRMS and 45 had SPMS. A battery consisting of 11 tests was used to evaluate cognitive function. We used 11 linear MRI measures and 7 indexes to assess brain atrophy. RESULTS Four cognitive tests and 3 linear MRI measures were able to distinguish RRMS from SPMS with the AUC >0.8 based on ROC analysis. Multiple logistic regression models were constructed to identify the best set of cognitive and MRI markers. The model, using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Huckman Index, showed the highest predictive ability: AUC=0.921 (p<0.001). We constructed a simple remission-progression index from the same 3 variables, which discriminated well between RRMS and SPMS: AUC=0.920 (p<0.001), maximal Youden Index=0.702, cut-off=1.68, sensitivity=79.1%, and specificity=91.1%. CONCLUSIONS The composite remission-progression index, using the RAVLT test, DSST test, and MRI Huckman Index, is highly accurate in discriminating between RRMS and SPMS.

  8. Optic nerve atrophy

    Science.gov (United States)

    Optic atrophy; Optic neuropathy ... There are many causes of optic atrophy. The most common is poor blood flow. This is called ischemic optic neuropathy. The problem most often affects older adults. ...

  9. Multiple System Atrophy (MSA)

    Science.gov (United States)

    Multiple system atrophy (MSA) Overview Multiple system atrophy (MSA) is a rare, degenerative neurological disorder affecting your body's involuntary (autonomic) functions, including blood pressure, breathing, bladder function and muscle ...

  10. Aberrant brain-stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Lee JH

    2016-08-01

    Full Text Available Ji Han Lee,1 Won Sang Jung,2 Woo Hee Choi,3 Hyun Kook Lim4 1Washington University in St Louis, St Louis, MO, USA; 2Department of Radiology, 3Department of Nuclear Medicine, 4Department of Psychiatry, Saint Vincent Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea Objective: Among patients with Alzheimer’s disease (AD, sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD.Materials and methods: In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology.Results: Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group.Conclusion: This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings. Keywords: Alzheimer’s disease, sleep, brain stem, MRI, shape analysis

  11. Word-stem tones cue suffixes in the brain.

    Science.gov (United States)

    Roll, Mikael; Söderström, Pelle; Horne, Merle

    2013-07-03

    High and low tones on Swedish word stems are associated with different classes of suffixes. We tested the electrophysiological effects of high and low stem tones as well as tonally cued and uncued suffixes. Two different tasks were used involving either choosing the suffix-dependent meaning of the words, or pressing a button when the word ended. To determine whether effects were in fact due to association of tones with lexical material, delexicalized stimuli were also used. High tones in lexical items produced an increase in the P2 component in both tasks, interpreted as showing passive anticipatory attention allocated to the associated upcoming suffix. This effect was absent for delexicalized forms, where instead an N1 increase was found for high tones, indicating that the high pitch was unexpected in the absence of lexical material, and did not lead to anticipatory attention. A P600 effect was found for uncued high-associated suffixes in the semantic task, which was also where the largest increase was found in reaction times. This suggests that the tonal cues were most important when participants were required to process the meaning of the words. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Image analysis of neural stem cell division patterns in the zebrafish brain.

    Science.gov (United States)

    Lupperger, Valerio; Buggenthin, Felix; Chapouton, Prisca; Marr, Carsten

    2017-11-10

    Proliferating stem cells in the adult body are the source of constant regeneration. In the brain, neural stem cells (NSCs) divide to maintain the stem cell population and generate neural progenitor cells that eventually replenish mature neurons and glial cells. How much spatial coordination of NSC division and differentiation is present in a functional brain is an open question. To quantify the patterns of stem cell divisions, one has to (i) identify the pool of NSCs that have the ability to divide, (ii) determine NSCs that divide within a given time window, and (iii) analyze the degree of spatial coordination. Here, we present a bioimage informatics pipeline that automatically identifies GFP expressing NSCs in three-dimensional image stacks of zebrafish brain from whole-mount preparations. We exploit the fact that NSCs in the zebrafish hemispheres are located on a two-dimensional surface and identify between 1,500 and 2,500 NSCs in six brain hemispheres. We then determine the position of dividing NSCs in the hemisphere by EdU incorporation into cells undergoing S-phase and calculate all pairwise NSC distances with three alternative metrics. Finally, we fit a probabilistic model to the observed spatial patterns that accounts for the non-homogeneous distribution of NSCs. We find a weak positive coordination between dividing NSCs irrespective of the metric and conclude that neither strong inhibitory nor strong attractive signals drive NSC divisions in the adult zebrafish brain. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  13. Identifying endogenous neural stem cells in the adult brain in vitro and in vivo: novel approaches.

    Science.gov (United States)

    Rueger, Maria Adele; Androutsellis-Theotokis, Andreas

    2013-01-01

    In the 1960s, Joseph Altman reported that the adult mammalian brain is capable of generating new neurons. Today it is understood that some of these neurons are derived from uncommitted cells in the subventricular zone lining the lateral ventricles, and the dentate gyrus of the hippocampus. The first area generates new neuroblasts which migrate to the olfactory bulb, whereas hippocampal neurogenesis seems to play roles in particular types of learning and memory. A part of these uncommitted (immature) cells is able to divide and their progeny can generate all three major cell types of the nervous system: neurons, astrocytes, and oligodendrocytes; these properties define such cells as neural stem cells. Although the roles of these cells are not yet clear, it is accepted that they affect functions including olfaction and learning/memory. Experiments with insults to the central nervous system also show that neural stem cells are quickly mobilized due to injury and in various disorders by proliferating, and migrating to injury sites. This suggests a role of endogenous neural stem cells in disease. New pools of stem cells are being discovered, suggesting an even more important role for these cells. To understand these cells and to coax them to contribute to tissue repair it would be very useful to be able to image them in the living organism. Here we discuss advances in imaging approaches as well as new concepts that emerge from stem cell biology with emphasis on the interface between imaging and stem cells.

  14. Long-term meditation is associated with increased gray matter density in the brain stem

    DEFF Research Database (Denmark)

    Vestergaard-Poulsen, Peter; Beek, Martijn van; Skewes, Joshua

    2009-01-01

    Extensive practice involving sustained attention can lead to changes in brain structure. Here, we report evidence of structural differences in the lower brainstem of participants engaged in the long-term practice of meditation. Using magnetic resonance imaging, we observed higher gray matter...... density in lower brain stem regions of experienced meditators compared with age-matched nonmeditators. Our findings show that long-term practitioners of meditation have structural differences in brainstem regions concerned with cardiorespiratory control. This could account for some...... of the cardiorespiratory parasympathetic effects and traits, as well as the cognitive, emotional, and immunoreactive impact reported in several studies of different meditation practices....

  15. 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

  16. Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

    Science.gov (United States)

    Roll, Lars; Faissner, Andreas

    2014-01-01

    The limited regeneration capacity of the adult central nervous system (CNS) requires strategies to improve recovery of patients. In this context, the interaction of endogenous as well as transplanted stem cells with their environment is crucial. An understanding of the molecular mechanisms could help to improve regeneration by targeted manipulation. In the course of reactive gliosis, astrocytes upregulate Glial fibrillary acidic protein (GFAP) and start, in many cases, to proliferate. Beside GFAP, subpopulations of these astroglial cells coexpress neural progenitor markers like Nestin. Although cells express these markers, the proportion of cells that eventually give rise to neurons is limited in many cases in vivo compared to the situation in vitro. In the first section, we present the characteristics of endogenous progenitor-like cells and discuss the differences in their neurogenic potential in vitro and in vivo. As the environment plays an important role for survival, proliferation, migration, and other processes, the second section of the review describes changes in the extracellular matrix (ECM), a complex network that contains numerous signaling molecules. It appears that signals in the damaged CNS lead to an activation and de-differentiation of astrocytes, but do not effectively promote neuronal differentiation of these cells. Factors that influence stem cells during development are upregulated in the damaged brain as part of an environment resembling a stem cell niche. We give a general description of the ECM composition, with focus on stem cell-associated factors like the glycoprotein Tenascin-C (TN-C). Stem cell transplantation is considered as potential treatment strategy. Interaction of transplanted stem cells with the host environment is critical for the outcome of stem cell-based therapies. Possible mechanisms involving the ECM by which transplanted stem cells might improve recovery are discussed in the last section. PMID:25191223

  17. Microinjection of membrane-impermeable molecules into single neural stem cells in brain tissue.

    Science.gov (United States)

    Wong, Fong Kuan; Haffner, Christiane; Huttner, Wieland B; Taverna, Elena

    2014-05-01

    This microinjection protocol allows the manipulation and tracking of neural stem and progenitor cells in tissue at single-cell resolution. We demonstrate how to apply microinjection to organotypic brain slices obtained from mice and ferrets; however, our technique is not limited to mouse and ferret embryos, but provides a means of introducing a wide variety of membrane-impermeable molecules (e.g., nucleic acids, proteins, hydrophilic compounds) into neural stem and progenitor cells of any developing mammalian brain. Microinjection experiments are conducted by using a phase-contrast microscope equipped with epifluorescence, a transjector and a micromanipulator. The procedure normally takes ∼2 h for an experienced researcher, and the entire protocol, including tissue processing, can be performed within 1 week. Thus, microinjection is a unique and versatile method for changing and tracking the fate of a cell in organotypic slice culture.

  18. Early changes of auditory brain stem evoked response after radiotherapy for nasopharyngeal carcinoma - a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Lau, S.K.; Wei, W.I.; Sham, J.S.T.; Choy, D.T.K.; Hui, Y. (Queen Mary Hospital, Hong Kong (Hong Kong))

    1992-10-01

    A prospective study of the effect of radiotherapy for nasopharyngeal carcinoma on hearing was carried out on 49 patients who had pure tone, impedance audiometry and auditory brain stem evoked response (ABR) recordings before, immediately, three, six and 12 months after radiotherapy. Fourteen patients complained of intermittent tinnitus after radiotherapy. We found that 11 initially normal ears of nine patients developed a middle ear effusion, three to six months after radiotherapy. There was mixed sensorineural and conductive hearing impairment after radiotherapy. Persistent impairment of ABR was detected immediately after completion of radiotherapy. The waves I-III and I-V interpeak latency intervals were significantly prolonged one year after radiotherapy. The study shows that radiotherapy for nasopharyngeal carcinoma impairs hearing by acting on the middle ear, the cochlea and the brain stem auditory pathway. (Author).

  19. Multiple cystic and focal encephalomalacia in infancy and childhood with brain stem damage.

    Science.gov (United States)

    Smith, J F; Rodeck, C

    1975-07-01

    Two cases are described in which damage to the brain stem was associated with extensive necrosis of the cerebral hemisphere. In the first case--a monochorionic twin--there was clear evidence that injury of an ischaemic or hypoxic type had occurred during fetal life and some evidence that an inadequate share of the placental circulation was an important aetiological factor. In the second case death occurred 4 yr after an asphyxial episode at birth. The lesions in the hemispheres and brain stem were extensive, although less than in the first example. The lesions are discussed in the context of our knowledge of the anatomy and physiology of the developing nervous system. Although they cannot as yet be fitted into the concepts of "critical periods" and "vulnerable periods" of development, this is perhaps because observations on human cases are scanty in comparison with the extensive animal studies which have been reported. The lesions are contrasted and compared with those seen in animals.

  20. Severe encephalopathy after high-dose chemotherapy with autologous stem cell support for brain tumours.

    Science.gov (United States)

    van den Berkmortel, F; Gidding, C; De Kanter, M; Punt, C J A

    2006-01-01

    Recurrent medulloblastoma carries a poor prognosis. Long-term survival has been obtained with high-dose chemotherapy with autologous stem cell transplantation and secondary irradiation. A 21-year-old woman with recurrent medulloblastoma after previous chemotherapy and radiotherapy is presented. The patient was treated with high-dose chemotherapy and autologous stem cell transplantation. She developed a severe treatment-related encephalopathy which affected her quality of life and neurocognitive functioning for the rest of her life. Possible causative factors are discussed and central nervous system toxicity by high-dose chemotherapy in brain tumour patients is reviewed. Case reports on severe central nervous system toxicity have been reported, but data from prospective studies on neurocognitive functioning are not available. These data strongly support a systematic long-term follow-up of brain tumour patients treated with high-dose chemotherapy with emphasis on neurocognitive function tests.

  1. Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Anna Kraft

    2017-03-01

    Full Text Available Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia. Using a newly established in vitro system we show that calcium waves induced in an astrocytic monolayer spread to neural stem and progenitor cells and increase their self-renewal as well as migratory behavior. These changes are due to an upregulation of the Notch signaling pathway. This introduces the concept of propagating astrocytic calcium waves transmitting brain injury signals over long distances.

  2. Study on diffusion tensor imaging combined with electrophysiological monitoring in brain stem cavernous hemangioma resection

    Directory of Open Access Journals (Sweden)

    Dong-sheng KONG

    2017-07-01

    Full Text Available Objective To evaluate the clinical application value of diffusion tensor imaging (DTI combined with electrophysiological monitoring in the resection of brain stem cavernous hemangioma (CM.    Methods There were 39 patients with brain stem cavernous hemangioma. DTI was performed before and during the operation. Diffusion tensor tractography (DTT was used to track fiber and reconstruct pyramidal tract. Intraoperative neurobehavioral monitoring was used to detect the changes of somatosensory-evoked potentials (SEP, motor - evoked potentials (MEP and brain stem auditory - evoked potentials (BAEP.    Results Of all the 39 patients, there was no significant change of BAEP during the operation, 5 patients (12.82% had abnormal SEP, 6 cases (15.38% had abnormalities in MEP monitoring, 2 cases (5.13% had reduced volumes of pyramidal tract proved by DTI. Intraoperative MRI confirmed 36 cases (92.31% had complete removal of lesions, and 3 cases (7.69% had subtotal resection. There were improvement of clinical symptoms in 29 cases (74.36% , no obvious changes in 4 cases (10.26% , postoperative facial paralysis in 3 cases (7.69%, worsened movement disorder in 2 cases (5.13%, death due to disorder of consciousness and pulmonary infection in one case (2.56% . Postoperative follow - up was 30 months in average. Glasgow Outcome Scale (GOS showed 27 cases (69.23% of Grade 5, 7 cases (17.95% of Grade 4, 4 cases (10.26% of Grade 3, and one case (2.56% of Grade 1.    Conclusions Combined use of intraoperative DTI and electrophysiological monitoring can safely and effectively remove brain stem cavernous hemangioma. DOI: 10.3969/j.issn.1672-6731.2017.05.010

  3. Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain

    Directory of Open Access Journals (Sweden)

    Marina E. Emborg

    2013-03-01

    Full Text Available The generation of induced pluripotent stem cells (iPSCs opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies.

  4. Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

    Science.gov (United States)

    Anselmi, L; Toti, L; Bove, C; Travagli, R A

    2017-11-01

    Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1) assess the gastric effects of brain stem DA application, 2) identify the DA receptor subtype, and, 3) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility.NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

  5. VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jinqiao, E-mail: jinqiao1977@163.com [Institute of Pediatrics, Children' s Hospital of Fudan University (China); Sha, Bin [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Zhou, Wenhao, E-mail: zhou_wenhao@yahoo.com.cn [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Yang, Yi [Institute of Pediatrics, Children' s Hospital of Fudan University (China)

    2010-03-26

    This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.

  6. Influence of Brain Stem on Axial and Hindlimb Spinal Locomotor Rhythm Generating Circuits of the Neonatal Mouse

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    Céline Jean-Xavier

    2018-02-01

    Full Text Available The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs during drug-induced fictive locomotor-like activity (LLA in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC and hindlimb MNs in lateral motor column (LMC. The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor.

  7. SOX5/6/21 Prevent Oncogene-Driven Transformation of Brain Stem Cells.

    Science.gov (United States)

    Kurtsdotter, Idha; Topcic, Danijal; Karlén, Alexandra; Singla, Bhumica; Hagey, Daniel W; Bergsland, Maria; Siesjö, Peter; Nistér, Monica; Carlson, Joseph W; Lefebvre, Veronique; Persson, Oscar; Holmberg, Johan; Muhr, Jonas

    2017-09-15

    Molecular mechanisms preventing self-renewing brain stem cells from oncogenic transformation are poorly defined. We show that the expression levels of SOX5, SOX6, and SOX21 (SOX5/6/21) transcription factors increase in stem cells of the subventricular zone (SVZ) upon oncogenic stress, whereas their expression in human glioma decreases during malignant progression. Elevated levels of SOX5/6/21 promoted SVZ cells to exit the cell cycle, whereas genetic ablation of SOX5/6/21 dramatically increased the capacity of these cells to form glioma-like tumors in an oncogene-driven mouse brain tumor model. Loss-of-function experiments revealed that SOX5/6/21 prevent detrimental hyperproliferation of oncogene expressing SVZ cells by facilitating an antiproliferative expression profile. Consistently, restoring high levels of SOX5/6/21 in human primary glioblastoma cells enabled expression of CDK inhibitors and decreased p53 protein turnover, which blocked their tumorigenic capacity through cellular senescence and apoptosis. Altogether, these results provide evidence that SOX5/6/21 play a central role in driving a tumor suppressor response in brain stem cells upon oncogenic insult. Cancer Res; 77(18); 4985-97. ©2017 AACR. ©2017 American Association for Cancer Research.

  8. Lobar atrophy without Pick bodies.

    Science.gov (United States)

    Hulette, C M; Crain, B J

    1992-01-01

    Four patients from the Kathleen Price Bryan Brain Bank with clinical Pick's syndrome are presented. Thorough neurological evaluation revealed no evidence of a movement disorder. The brains showed marked knife-blade type atrophy of the frontal and temporal lobes with relative sparing of the superior temporal gyrus and parietal and occipital lobes. There was marked caudate atrophy in all four. Histologically there was severe neuronal loss and gemistocytic astrocytosis in the involved areas with marked myelin pallor in the deep white matter and subcortical gliosis. There was sometimes marked spongiform change in cortical layer 2. There was severe neuronal loss and gliosis of the caudate nucleus. The gross and microscopic features were characteristic of Pick's disease except that careful search failed to uncover either Pick's bodies or Pick's cells. Review of the literature revealed that fronto-temporal cortical and caudate atrophy with clinical features of Pick's disease has received many different names including Pick's disease type C, Pick's disease type II, progressive subcortical gliosis, presenile glial dystrophy, long duration Creutzfeldt-Jakob disease, frontal lobe degeneration, dysphasic dementia, and dementia lacking distinctive histologic features. Nevertheless, the morphologic findings in the present cases so closely resemble Pick's disease that they may well represent endstage Pick's disease. In our experience, such cases account for a significant proportion of non-Alzheimer disease dementia.

  9. Analysis of Gene Expression Profiles in the Human Brain Stem, Cerebellum and Cerebral Cortex.

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    Lei Chen

    Full Text Available The human brain is one of the most mysterious tissues in the body. Our knowledge of the human brain is limited due to the complexity of its structure and the microscopic nature of connections between brain regions and other tissues in the body. In this study, we analyzed the gene expression profiles of three brain regions-the brain stem, cerebellum and cerebral cortex-to identify genes that are differentially expressed among these different brain regions in humans and to obtain a list of robust, region-specific, differentially expressed genes by comparing the expression signatures from different individuals. Feature selection methods, specifically minimum redundancy maximum relevance and incremental feature selection, were employed to analyze the gene expression profiles. Sequential minimal optimization, a machine-learning algorithm, was employed to examine the utility of selected genes. We also performed a literature search, and we discuss the experimental evidence for the important physiological functions of several highly ranked genes, including NR2E1, DAO, and LRRC7, and we give our analyses on a gene (TFAP2B that have not been investigated or experimentally validated. As a whole, the results of our study will improve our ability to predict and understand genes related to brain regionalization and function.

  10. HTLV-I associated myelopathy with multiple spotty areas in cerebral white matter and brain stem by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Yasuo; Takahashi, Mitsuo; Yoshikawa, Hiroo; Yorifuji, Shirou; Tarui, Seiichiro

    1988-01-01

    A 48-year-old woman was admitted with complaints of urinary incontinence and gait disturbance, both of which had progressed slowly without any sign of remission. Family history was not contributory. Neurologically, extreme spasticity was recoginized in the lower limbs. Babinski sign was positive bilaterally. Flower-like atypical lymphocytes were seen in blood. Positive anti-HTLV-I antibody was confirmed in serum and spinal fluid by western blot. She was diagnosed as having HTLV-I associated myelopathy (HAM). CT reveald calcification in bilateral globus pallidus, and MRI revealed multiple spotty areas in cerebral white matter and brain stem, but no spinal cord lesion was detectable. Electrophysiologically, brain stem auditory evoked potential (BAEP) suggested the presence of bilateral brain stem lesions. Neither median nor posterior tibial nerve somatosensory evoked potentials were evoked, a finding suggesting the existence of spinal cord lesion. In this case, the lesion was not confined to spinal cord, it was also observed in brain stem and cerebral white matter. Such distinct lesions in cerebral white matter and brain stem have not been reported in patients with HAM. It is suggested that HTLV-I is probably associated with cerebral white matter and brain stem.

  11. The usefulness of a computerized tomographic scan taken parallel to the clivus in the management of brain-stem lesions

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Akio; Mishima, Kazuhiko; Miyagawa, Naohisa; Aritake, Kouichi; Segawa, Hiromu; Sano, Keiji (Fuji Brain Instutue and Hospital, Shizuoka (Japan))

    1989-04-01

    It is important to detect the definite sites and extent of lesions in the management of brainstem infarction. While axial computerized tomographic scan (axial CT) has usually been used to map brain-stem lesions, it often fails to show small lesions or their longitudinal extent. In this report, the usefulness of CT scan using scan slices taken parallel to the clivus (clival CT) is evaluated in cases of brain-stem infarction. Clival CT was performed with the patient in a supine position, with as much neck flexion as possible. CT slices were taken parallel to the clivus (orbito-meatal line, 35-50 deg.). Both axial and clival CT scans were performed in 25 patients with brain-stem infarctions. Axial CT was most useful in detecting small lesions located in the ventral pons and in showing the anatomical structure which was involved. On the other hand, clival CT was superior in demonstrating the longitudinal extent of infarctions, especially in the midbrain or thalamus. In cases with major brain-stem infarctions or in cases with associated cerebellar lesions, the combination of axial and clival CT shows the configuration and continuity of the lesions clearly. Therefore, clival CT, when used with axial CT, clearly shows the three-dimensional extent of brain-stem infarctions; this technique is also recommended when managing other types of brain-stem disease. In addition, it is important to select appropriate CT slice angles in order to demonstrate the anatomical structure of interest. (author).

  12. A novel fluorescent reporter CDy1 enriches for neural stem cells derived from the murine brain.

    Science.gov (United States)

    Vukovic, Jana; Bedin, Anne-Sophie; Bartlett, Perry F; Osborne, Geoffrey W

    2013-08-15

    Neurogenesis occurs continuously in two brain regions of adult mammals, underpinned by a pool of resident neural stem cells (NSCs) that can differentiate into all neural cell types. To advance our understanding of NSC function and to develop therapeutic and diagnostic approaches, it is important to accurately identify and enrich for NSCs. There are no definitive markers for the identification and enrichment of NSCs present in the mouse brain. Recently, a fluorescent rosamine dye, CDy1, has been identified as a label for pluripotency in cultured human embryonic and induced pluripotent stem cells. As similar cellular characteristics may enable the uptake and retention of CDy1 by other stem cell populations, we hypothesized that this dye may also enrich for primary NSCs from the mouse brain. Because the subventricular zone (SVZ) and the hippocampus represent brain regions that are highly enriched for NSCs in adult mammals, we sampled cells from these areas to test this hypothesis. These experiments revealed that CDy1 staining indeed allows for enrichment and selection of all neurosphere-forming cells from both the SVZ and the hippocampus. We next examined the effectiveness of CDy1 to select for NSCs derived from the SVZ of aged animals, where the total pool of NSCs present is significantly lower than in young animals. We found that CDy1 effectively labels the NSCs in adult and aged animals as assessed by the neurosphere assay and reflects the numbers of NSCs present in aged animals. CDy1, therefore, appears to be a novel marker for enrichment of NSCs in primary brain tissue preparations.

  13. Monitoring the Bystander Killing Effect of Human Multipotent Stem Cells for Treatment of Malignant Brain Tumors

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    Cindy Leten

    2016-01-01

    Full Text Available Tumor infiltrating stem cells have been suggested as a vehicle for the delivery of a suicide gene towards otherwise difficult to treat tumors like glioma. We have used herpes simplex virus thymidine kinase expressing human multipotent adult progenitor cells in two brain tumor models (hU87 and Hs683 in immune-compromised mice. In order to determine the best time point for the administration of the codrug ganciclovir, the stem cell distribution and viability were monitored in vivo using bioluminescence (BLI and magnetic resonance imaging (MRI. Treatment was assessed by in vivo BLI and MRI of the tumors. We were able to show that suicide gene therapy using HSV-tk expressing stem cells can be followed in vivo by MRI and BLI. This has the advantage that (1 outliers can be detected earlier, (2 GCV treatment can be initiated based on stem cell distribution rather than on empirical time points, and (3 a more thorough follow-up can be provided prior to and after treatment of these animals. In contrast to rodent stem cell and tumor models, treatment success was limited in our model using human cell lines. This was most likely due to the lack of immune components in the immune-compromised rodents.

  14. Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

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    Mohammad Reza Nikravesh

    2011-11-01

    Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

  15. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Romeo Cecchelli

    Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

  16. The exon junction complex component Magoh controls brain size by regulating neural stem cell division

    Science.gov (United States)

    Silver, Debra L.; Watkins-Chow, Dawn E.; Schreck, Karisa C.; Pierfelice, Tarran J.; Larson, Denise M.; Burnetti, Anthony J.; Liaw, Hung-Jiun; Myung, Kyungjae; Walsh, Christopher A.; Gaiano, Nicholas; Pavan, William J.

    2010-01-01

    Summary Brain structure and size requires precise division of neural stem cells (NSCs), which self-renew and generate intermediate neural progenitors (INPs) and neurons. The factors that regulate NSCs remain poorly understood, as do mechanistic explanations of how aberrant NSC division causes reduced brain size as seen in microcephaly. Here we demonstrate that Magoh, a component of the exon junction complex (EJC) that binds RNA, controls mouse cerebral cortical size by regulating NSC division. Magoh haploinsufficiency causes microcephaly due to INP depletion and neuronal apoptosis. Defective mitosis underlies these phenotypes as depletion of EJC components disrupts mitotic spindle orientation and integrity, chromosome number, and genomic stability. In utero rescue experiments revealed that a key function of Magoh is to control levels of the microcephaly-associated protein, LIS1, during neurogenesis. This study uncovers new requirements for the EJC in brain development, NSC maintenance, and mitosis, thus implicating this complex in the pathogenesis of microcephaly. PMID:20364144

  17. Classic and novel stem cell niches in brain homeostasis and repair.

    Science.gov (United States)

    Lin, Ruihe; Iacovitti, Lorraine

    2015-12-02

    Neural stem cells (NSCs) critical for the continued production of new neurons and glia are sequestered in distinct areas of the brain called stem cell niches. Until recently, only two forebrain sites, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus, have been recognized adult stem cell niches (Alvarez-Buylla and Lim, 2004; Doetsch et al., 1999a, 1999b; Doetsch, 2003a, 2003b; Lie et al., 2004; Ming and Song, 2005). Nonetheless, the last decade has been witness to a growing literature suggesting that in fact the adult brain contains stem cell niches along the entire extent of the ventricular system. These niches are capable of widespread neurogenesis and gliogenesis, particularly after injury (Barnabé-Heider et al., 2010; Carlén et al., 2009; Decimo et al., 2012; Lin et al., 2015; Lindvall and Kokaia, 2008; Robins et al., 2013) or other inductive stimuli (Bennett et al., 2009; Cunningham et al., 2012; Decimo et al., 2011; Kokoeva et al., 2007, 2005; Lee et al., 2012a, 2012b; Migaud et al., 2010; Pencea et al., 2001b; Sanin et al., 2013; Suh et al., 2007; Sundholm-Peters et al., 2004; Xu et al., 2005; Zhang et al., 2007). This review focuses on the role of these novel and classic brain niches in maintaining adult neurogenesis and gliogenesis in response to normal physiological and injury-related pathological cues. This article is part of a Special Issue entitled SI: Neuroprotection. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Dominant optic atrophy

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    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

  19. Dominant optic atrophy.

    Science.gov (United States)

    Lenaers, Guy; Hamel, Christian; Delettre, Cécile; Amati-Bonneau, Patrizia; Procaccio, Vincent; Bonneau, Dominique; Reynier, Pascal; Milea, Dan

    2012-07-09

    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. 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. 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. 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. Patients are usually diagnosed during their early childhood, because of bilateral, mild, otherwise unexplained visual loss related to optic discs

  20. 3D culture of murine neural stem cells on decellularized mouse brain sections.

    Science.gov (United States)

    De Waele, Jorrit; Reekmans, Kristien; Daans, Jasmijn; Goossens, Herman; Berneman, Zwi; Ponsaerts, Peter

    2015-02-01

    Transplantation of neural stem cells (NSC) in diseased or injured brain tissue is widely studied as a potential treatment for various neurological pathologies. However, effective cell replacement therapy relies on the intrinsic capacity of cellular grafts to overcome hypoxic and/or immunological barriers after transplantation. In this context, it is hypothesized that structural support for grafted NSC will be of utmost importance. With this study, we present a novel decellularization protocol for 1.5 mm thick mouse brain sections, resulting in the generation of acellular three-dimensional (3D) brain sections. Next, the obtained 3D brain sections were seeded with murine NSC expressing both the eGFP and luciferase reporter proteins (NSC-eGFP/Luc). Using real-time bioluminescence imaging, the survival and growth of seeded NSC-eGFP/Luc cells was longitudinally monitored for 1-7 weeks in culture, indicating the ability of the acellular brain sections to support sustained ex vivo growth of NSC. Next, the organization of a 3D maze-like cellular structure was examined using confocal microscopy. Moreover, under mitogenic stimuli (EGF and hFGF-2), most cells in this 3D culture retained their NSC phenotype. Concluding, we here present a novel protocol for decellularization of mouse brain sections, which subsequently support long-term 3D culture of undifferentiated NSC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Cognition, brain atrophy, and cerebrospinal fluid biomarkers changes from preclinical to dementia stage of Alzheimer's disease and the influence of apolipoprotein e.

    Science.gov (United States)

    Susanto, Thomas Adi Kurnia; Pua, Emmanuel Peng Kiat; Zhou, Juan

    2015-01-01

    Knowledge of Alzheimer's disease (AD) manifestation in the pre-dementia stage facilitates the selection of appropriate measures for early detection and disease progression. To examine the trajectories of cognitive performance, gray matter volume (GMV), and cerebrospinal fluid (CSF) biomarkers, together with the influence of apolipoprotein E (APOE) in subjects with amyloid-β (Aβ) deposits across the pre-clinical to dementia stages of AD. 356 subjects were dichotomized into Aβ+ and Aβ- groups based on their CSF Aβ1-42 level. We derived AD-related atrophic regions (AD-ROIs) using the voxel-based morphometry approach. We characterized the trajectories of cognitive scores, GMV at AD-ROIs, and CSF biomarkers from preclinical to disease stages in Aβ+ subjects. The effect of APOE ε4 genotype on these trajectories was examined. Impairments in executive functioning/processing speed (EF/PS) and atrophy at the right supramarginal/inferior parietal gyrus were detected in cognitively normal Aβ+ subjects. Together with the APOE ε4 carrier status, these measures showed potential to identify cognitively normal elderly with abnormal CSF Aβ1-42 level in another independent cohort. Subsequently, impairment in memory, visuospatial, language, and attention as well as atrophy in the temporal lobe, thalamus, and mid-cingulate cortex were detectable in Aβ+ mild cognitive impairment (MCI) subjects. In MCI and dementia Aβ+ subjects, ε4 carriers had more severe atrophy of the medial temporal lobe and memory impairment but higher EF/PS compared to non-carriers. EF/PS decline and right parietal atrophy might act as non-invasive screening tests for abnormal amyloid deposition in cognitively normal elderly. APOE modulation on subsequent trajectories in cognition and atrophy should be taken into account when analyzing disease progression.

  2. Mannitol-Enhanced Delivery of Stem Cells and Their Growth Factors Across the Blood–Brain Barrier

    Science.gov (United States)

    Gonzales-Portillo, Gabriel S.; Sanberg, Paul R.; Franzblau, Max; Gonzales-Portillo, Chiara; Diamandis, Theo; Staples, Meaghan; Sanberg, Cyndy D.; Borlongan, Cesar V.

    2014-01-01

    Ischemic brain injury in adults and neonates is a significant clinical problem with limited therapeutic interventions. Currently, clinicians have only tPA available for stroke treatment and hypothermia for cerebral palsy. Owing to the lack of treatment options, there is a need for novel treatments such as stem cell therapy. Various stem cells including cells from embryo, fetus, perinatal, and adult tissues have proved effective in preclinical and small clinical trials. However, a limiting factor in the success of these treatments is the delivery of the cells and their by-products (neurotrophic factors) into the injured brain. We have demonstrated that mannitol, a drug with the potential to transiently open the blood–brain barrier and facilitate the entry of stem cells and trophic factors, as a solution to the delivery problem. The combination of stem cell therapy and mannitol may improve therapeutic outcomes in adult stroke and neonatal cerebral palsy. PMID:24480552

  3. 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 ...

  4. Long-term impact of radiation on the stem cell and oligodendrocyte precursors in the brain.

    Directory of Open Access Journals (Sweden)

    Georgia Panagiotakos

    Full Text Available The cellular basis of long term radiation damage in the brain is not fully understood.We administered a dose of 25Gy to adult rat brains while shielding the olfactory bulbs. Quantitative analyses were serially performed on different brain regions over 15 months. Our data reveal an immediate and permanent suppression of SVZ proliferation and neurogenesis. The olfactory bulb demonstrates a transient but remarkable SVZ-independent ability for compensation and maintenance of the calretinin interneuron population. The oligodendrocyte compartment exhibits a complex pattern of limited proliferation of NG2 progenitors but steady loss of the oligodendroglial antigen O4. As of nine months post radiation, diffuse demyelination starts in all irradiated brains. Counts of capillary segments and length demonstrate significant loss one day post radiation but swift and persistent recovery of the vasculature up to 15 months post XRT. MRI imaging confirms loss of volume of the corpus callosum and early signs of demyelination at 12 months. Ultrastructural analysis demonstrates progressive degradation of myelin sheaths with axonal preservation. Areas of focal necrosis appear beyond 15 months and are preceded by widespread demyelination. Human white matter specimens obtained post-radiation confirm early loss of oligodendrocyte progenitors and delayed onset of myelin sheath fragmentation with preserved capillaries.This study demonstrates that long term radiation injury is associated with irreversible damage to the neural stem cell compartment in the rodent SVZ and loss of oligodendrocyte precursor cells in both rodent and human brain. Delayed onset demyelination precedes focal necrosis and is likely due to the loss of oligodendrocyte precursors and the inability of the stem cell compartment to compensate for this loss.

  5. Mesenchymal stem cells as a treatment for neonatal ischemic brain damage.

    Science.gov (United States)

    van Velthoven, Cindy T J; Kavelaars, Annemieke; Heijnen, Cobi J

    2012-04-01

    Mesenchymal stem cell (MSC)-based therapies have been proven effective in experimental models of numerous disorders. Treatment of ischemic brain injury by transplantation of MSCs in neonatal animal models has been shown to be effective in reducing lesion volume and improving functional outcome. The beneficial effect of MSC transplantation to treat neonatal brain injury might be explained by the great plasticity of the neonatal brain. The neonatal brain is still in a developmentally active phase, leading to a better efficiency of MSC transplantation than that observed in experiments using adult models of stroke. Enhanced neurogenesis and axonal remodeling likely underlie the improved functional outcome following MSC treatment after neonatal hypoxic-ischemic (HI) brain injury. With respect to the mechanism of repair by MSCs, MSCs do not survive long term and replace damaged tissue themselves. We propose that MSCs react to the needs of the ischemic cerebral environment by secretion of several growth factors, cytokines, and other bioactive molecules to regulate damage and repair processes. Parenchymal cells react to the secretome of the MSCs and contribute to stimulate repair processes. These intrinsic adaptive properties of MSCs make them excellent candidates for a novel therapy to treat the devastating effects of HI encephalopathy in the human neonate.

  6. Stemming the Impact of Health Professional Brain Drain from Africa: A Systemic Review of Policy Options.

    Science.gov (United States)

    Zimbudzi, Edward

    2013-06-25

    Africa has been losing professionally trained health workers who are the core of the health system of this continent for many years. Faced with an increased burden of disease and coupled by a massive exodus of the health workforce, the health systems of many African nations are risking complete paralysis. Several studies have suggested policy options to reduce brain drain from Africa. The purpose of this paper is to review possible policies, which can stem the impact of health professional brain drain from Africa. A systemic literature review was conducted. Cinahl, Science Direct and PubMed databases were searched with the following terms: health professional brain drain from Africa and policies for reducing impact of brain drain from Africa. References were also browsed for relevant articles. A total of 425 articles were available for the study but only 23 articles met the inclusion criteria. The review identified nine policy options, which were being implemented in Africa, but the most common was task shifting which had success in several African countries. This review has demonstrated that there is considerable consensus on task shifting as the most appropriate and sustainable policy option for reducing the impact of health professional brain drain from Africa.

  7. Stemming the impact of health professional brain drain from Africa: a systemic review of policy options

    Directory of Open Access Journals (Sweden)

    Edward Zimbudzi

    2013-06-01

    Full Text Available Africa has been losing professionally trained health workers who are the core of the health system of this continent for many years. Faced with an increased burden of disease and coupled by a massive exodus of the health workforce, the health systems of many African nations are risking complete paralysis. Several studies have suggested policy options to reduce brain drain from Africa. The purpose of this paper is to review possible policies, which can stem the impact of health professional brain drain from Africa. A systemic literature review was conducted. Cinahl, Science Direct and PubMed databases were searched with the following terms: health professional brain drain from Africa and policies for reducing impact of brain drain from Africa. References were also browsed for relevant articles. A total of 425 articles were available for the study but only 23 articles met the inclusion criteria. The review identified nine policy options, which were being implemented in Africa, but the most common was task shifting which had success in several African countries. This review has demonstrated that there is considerable consensus on task shifting as the most appropriate and sustainable policy option for reducing the impact of health professional brain drain from Africa.

  8. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

    2008-01-01

    differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic......-culture, large numbers of tyrosine hydroxylase (TH)-immunoreactive, catecholaminergic cells could be found underneath individual striatal slices. Cell counting revealed that up to 25.3% (average 16.1%) of the total number of cells in these areas were TH-positive, contrasting a few TH-positive cells (

  9. Circumventricular organs: a novel site of neural stem cells in the adult brain.

    Science.gov (United States)

    Bennett, Lori; Yang, Ming; Enikolopov, Grigori; Iacovitti, Lorraine

    2009-07-01

    Neurogenesis in the adult mammalian nervous system is now well established in the subventricular zone of the anterolateral ventricle and subgranular zone of the hippocampus. In these regions, neurons are thought to arise from neural stem cells, identified by their expression of specific intermediate filament proteins (nestin, vimentin, GFAP) and transcription factors (Sox2). In the present study, we show that in adult rat and mouse, the circumventricular organs (CVOs) are rich in nestin+, GFAP+, vimentin+ cells which express Sox2 and the cell cycle-regulating protein Ki67. In culture, these cells proliferate as neurospheres and express neuronal (doublecortin+, beta-tubulin III+) and glial (S100beta+, GFAP+, RIP+) phenotypic traits. Further, our in vivo studies using bromodeoxyuridine show that CVO cells proliferate and undergo constitutive neurogenesis and gliogenesis. These findings suggest that CVOs may constitute a heretofore unknown source of stem/progenitor cells, capable of giving rise to new neurons and/or glia in the adult brain.

  10. The extracellular matrix niche microenvironment of neural and cancer stem cells in the brain.

    Science.gov (United States)

    Reinhard, Jacqueline; Brösicke, Nicole; Theocharidis, Ursula; Faissner, Andreas

    2016-12-01

    Numerous studies demonstrated that neural stem cells and cancer stem cells (NSCs/CSCs) share several overlapping characteristics such as self-renewal, multipotency and a comparable molecular repertoire. In addition to the intrinsic cellular properties, NSCs/CSCs favor a similar environment to acquire and maintain their characteristics. In the present review, we highlight the shared properties of NSCs and CSCs in regard to their extracellular microenvironment called the NSC/CSC niche. Moreover, we point out that extracellular matrix (ECM) molecules and their complementary receptors influence the behavior of NSCs/CSCs as well as brain tumor progression. Here, we focus on the expression profile and functional importance of the ECM glycoprotein tenascin-C, the chondroitin sulfate proteoglycan DSD-1-PG/phosphacan but also on other important glycoprotein/proteoglycan constituents. Within this review, we specifically concentrate on glioblastoma multiforme (GBM). GBM is the most common malignant brain tumor in adults and is associated with poor prognosis despite intense and aggressive surgical and therapeutic treatment. Recent studies indicate that GBM onset is driven by a subpopulation of CSCs that display self-renewal and recapitulate tumor heterogeneity. Based on the CSC hypothesis the cancer arises just from a small subpopulation of self-sustaining cancer cells with the exclusive ability to self-renew and maintain the tumor. Besides the fundamental stem cell properties of self-renewal and multipotency, GBM stem cells share further molecular characteristics with NSCs, which we would like to review in this article. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Dosimetric analysis of trigeminal nerve, brain stem doses in CyberKnife radiosurgery of trigeminal neuralgia.

    Science.gov (United States)

    Sudahar, H; Kurup, P G G; Murali, V; Velmurugan, J

    2012-07-01

    CyberKnife radiosurgery treatment of Trigeminal neuralgia (TN) is performed as a non-invasive image guided procedure. The prescription dose for TN is very high. The brainstem is the adjacent critical organ at risk (OAR) which is prone to receive the very high target dose of TN. The present study is to analyze the dose distribution inside the tiny trigeminal nerve target and also to analyze the dose fall off in the brain stem. Seven TN cases treated between November 2010 and January 2012 were taken for this study retrospectively. The treatment plans were analyzed for target dose conformity, homogeneity and dose coverage. In the brainstem the volume doses D(1%), D(2%) were taken for analyzing the higher doses in the brain stem. The dose fall off was analyzed in terms of D(5%) and D(10%). The mean value of maximum dose within the trigeminal nerve target was 73.5±2.1Gy (P=0.0007) and the minimum dose was 50.0±4.1Gy (P=0.1315). The mean conformity index was 2.19 and the probable reason could be the smallest CyberKnife collimator of 5mm used in the treatment plan. The mean D(1%), of the brainstem was 10.5± 2.1Gy (P=0.5316) and the mean value of the maximum point dose within the brainstem was 35.6±3.8Gy. This shows the degree of dose fall off within the brainstem. Though the results of the present study are showing superior sparing of brain stem and reasonable of target coverage, it is necessary to execute the treatment plan with greater accuracy in CyberKnife as the immobilization is noninvasive and frameless.

  12. MRI Visual Ratings of Brain Atrophy and White Matter Hyperintensities across the Spectrum of Cognitive Decline Are Differently Affected by Age and Diagnosis

    Directory of Open Access Journals (Sweden)

    Hanneke F. M. Rhodius-Meester

    2017-05-01

    Full Text Available Aim: To assess the associations of age and diagnosis with visual ratings of medial temporal lobe atrophy (MTA, parietal atrophy (PA, global cortical atrophy (GCA, and white matter hyperintensities (WMH and to investigate their clinical value in a large memory clinic cohort.Methods: We included 2,934 patients (age 67 ± 9 years; 1,391 [47%] female; MMSE 24 ± 5 from the Amsterdam Dementia Cohort (1,347 dementia due to Alzheimer's disease [AD]; 681 mild cognitive impairment [MCI]; 906 controls with subjective cognitive decline. We analyzed the effect of age, APOE e4 and diagnosis on visual ratings using linear regression analyses. Subsequently, we compared diagnostic and predictive value in three age-groups (<65 years, 65–75 years, and >75 years.Results: Linear regression analyses showed main effects of age and diagnosis and an interaction age*diagnosis for MTA, PA, and GCA. For MTA the interaction effect indicated steeper age effects in MCI and AD than in controls. PA and GCA increased with age in MCI and controls, while AD patients have a high score, regardless of age. For WMH we found a main effect of age, but not of diagnosis. For MTA, GCA and PA, diagnostic value was best in patients <65 years (optimal cut-off: ≥1. PA and GCA only discriminated in patients <65 years and MTA in patients <75 years. WMH did not discriminate at all. Taking into account APOE did not affect the identified optimal cut-offs. When we used these scales to predict progression in MCI using Cox proportional hazard models, only MTA (cut-off ≥2 had any predictive value, restricted to patients >75 years.Conclusion: Visual ratings of atrophy and WMH were differently affected by age and diagnosis, requiring an age-specific approach in clinical practice. Their diagnostic value seems strongest in younger patients.

  13. Neural Stem Cell Transplantation Promotes Functional Recovery from Traumatic Brain Injury via Brain Derived Neurotrophic Factor-Mediated Neuroplasticity.

    Science.gov (United States)

    Xiong, Liu-Lin; Hu, Yue; Zhang, Piao; Zhang, Zhuo; Li, Li-Hong; Gao, Guo-Dong; Zhou, Xin-Fu; Wang, Ting-Hua

    2017-04-18

    Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral deficits. Previous evidences have suggested that neural stem cell (NSC) transplantation could facilitate functional recovery from brain insults, but their underlying mechanisms remains to be elucidated. Here, we established TBI model by an electromagnetic-controlled cortical impact device in the rats. Then, 5 μl NSCs (5.0 × 10 5 /μl), derived from green fluorescent protein (GFP) transgenic mouse, was transplanted into the traumatic brain regions of rats at 24 h after injury. After differentiation of the NSCs was determined using immunohistochemistry, neurological severity scores (NSS) and rotarod test were conducted to detect the neurological behavior. Western blot and RT-PCR as well as ELASA were used to evaluate the expression of synaptophysin and brain-derived neurotrophic factor (BDNF). In order to elucidate the role of BDNF on the neural recovery after NSC transplantation, BDNF knockdown in NSC was performed and transplanted into the rats with TBI, and potential mechanism for BDNF knockdown in the NSC was analyzed using microassay analysis. Meanwhile, BDNF antibody blockade was conducted to further confirm the effect of BDNF on neural activity. As a result, an increasing neurological function improvement was seen in NSC transplanted rats, which was associated with the upregulation of synaptophysin and BDNF expression. Moreover, transplantation of BDNF knockdown NSCs and BDNF antibody block reduced not only the level of synaptophysin but also exacerbated neurological function deficits. Microassay analysis showed that 14 genes such as Wnt and Gsk3-β were downregulated after BDNF knockdown. The present data therefore showed that BDNF-mediated neuroplasticity underlie the mechanism of NSC transplantation for the treatment of TBI in adult rats.

  14. Music modulation of pain perception and pain-related activity in the brain, brain stem, and spinal cord: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Dobek, Christine E; Beynon, Michaela E; Bosma, Rachael L; Stroman, Patrick W

    2014-10-01

    The oldest known method for relieving pain is music, and yet, to date, the underlying neural mechanisms have not been studied. Here, we investigate these neural mechanisms by applying a well-defined painful stimulus while participants listened to their favorite music or to no music. Neural responses in the brain, brain stem, and spinal cord were mapped with functional magnetic resonance imaging spanning the cortex, brain stem, and spinal cord. Subjective pain ratings were observed to be significantly lower when pain was administered with music than without music. The pain stimulus without music elicited neural activity in brain regions that are consistent with previous studies. Brain regions associated with pleasurable music listening included limbic, frontal, and auditory regions, when comparing music to non-music pain conditions. In addition, regions demonstrated activity indicative of descending pain modulation when contrasting the 2 conditions. These regions include the dorsolateral prefrontal cortex, periaqueductal gray matter, rostral ventromedial medulla, and dorsal gray matter of the spinal cord. This is the first imaging study to characterize the neural response of pain and how pain is mitigated by music, and it provides new insights into the neural mechanism of music-induced analgesia within the central nervous system. This article presents the first investigation of neural processes underlying music analgesia in human participants. Music modulates pain responses in the brain, brain stem, and spinal cord, and neural activity changes are consistent with engagement of the descending analgesia system. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  15. Neural stem cells sustain natural killer cells that dictate recovery from brain inflammation

    Science.gov (United States)

    Liu, Qiang; Sanai, Nader; Jin, Wei-Na; La Cava, Antonio; Van Kaer, Luc; Shi, Fu-Dong

    2017-01-01

    Recovery from organ-specific autoimmune diseases largely relies on the mobilization of endogenous repair mechanisms and local factors that control them. Natural killer (NK) cells are swiftly mobilized to organs targeted by autoimmunity and typically undergo numerical contraction when inflammation wanes. We report the unexpected finding that NK cells are retained in the brain subventricular zone (SVZ) during the chronic phase of multiple sclerosis in humans and its animal model in mice. These NK cells were found preferentially in close proximity to SVZ neural stem cells (NSCs) that produce interleukin-15 and sustain functionally competent NK cells. Moreover, NK cells limited the reparative capacity of NSCs following brain inflammation. These findings reveal that reciprocal interactions between NSCs and NK cells regulate neurorepair. PMID:26752157

  16. Hallmarks of Alzheimer's Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain.

    Science.gov (United States)

    Espuny-Camacho, Ira; Arranz, Amaia M; Fiers, Mark; Snellinx, An; Ando, Kunie; Munck, Sebastian; Bonnefont, Jerome; Lambot, Laurie; Corthout, Nikky; Omodho, Lorna; Vanden Eynden, Elke; Radaelli, Enrico; Tesseur, Ina; Wray, Selina; Ebneth, Andreas; Hardy, John; Leroy, Karelle; Brion, Jean-Pierre; Vanderhaeghen, Pierre; De Strooper, Bart

    2017-03-08

    Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of their natural environment. Here we transplanted human PSC-derived cortical neuronal precursors into the brain of a murine AD model. Human neurons differentiate and integrate into the brain, express 3R/4R Tau splice forms, show abnormal phosphorylation and conformational Tau changes, and undergo neurodegeneration. Remarkably, cell death was dissociated from tangle formation in this natural 3D model of AD. Using genome-wide expression analysis, we observed upregulation of genes involved in myelination and downregulation of genes related to memory and cognition, synaptic transmission, and neuron projection. This novel chimeric model for AD displays human-specific pathological features and allows the analysis of different genetic backgrounds and mutations during the course of the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Reelin signaling in the migration of ventral brain stem and spinal cord neurons

    Directory of Open Access Journals (Sweden)

    Sandra eBlaess

    2016-03-01

    Full Text Available The extracellular matrix protein Reelin is an important orchestrator of neuronal migration during the development of the central nervous system. While its role and mechanism of action have been extensively studied and reviewed in the formation of dorsal laminar brain structures like the cerebral cortex, hippocampus, and cerebellum, its functions during the neuronal migration events that result in the nuclear organization of the ventral central nervous system are less well understood. In an attempt to delineate an underlying pattern of Reelin action in the formation of neuronal cell clusters, this review highlights the role of Reelin signaling in the migration of neuronal populations that originate in the ventral brain stem and the spinal cord.

  18. Ethanol alters cell fate of fetal human brain-derived stem and progenitor cells.

    Science.gov (United States)

    Vangipuram, Sharada D; Lyman, William D

    2010-09-01

    Prenatal ethanol (ETOH) exposure can lead to fetal alcohol spectrum disorder (FASD). We previously showed that ETOH alters cell adhesion molecule gene expression and increases neurosphere size in fetal brain-derived neural stem cells (NSC). Here, our aim was to determine the effect of ETOH on the cell fate of NSC, premature glial-committed precursor cells (GCP), and premature neuron-committed progenitor cells (NCP). NSC, GCP, and NCP were isolated from normal second-trimester fetal human brains (n = 3) by positive selection using magnetic microbeads labeled with antibodies to CD133 (NSC), A2B5 (GCP), or PSA-NCAM (NCP). As a result of the small percentage in each brain, NSC were cultured in mitogenic media for 72 hours to produce neurospheres. The neurospheres from NSC and primary isolates of GCP and NCP were used for all experiments. Equal numbers of the 3 cell types were treated either with mitogenic media or with differentiating media, each containing 0 or 100 mM ETOH, for 120 hours. Expression of Map2a, GFAP, and O4 was determined by immunoflourescence microscopy and western blot analysis. Fluorescence intensities were quantified using Metamorph software by Molecular Devices, and the bands of western blots were quantified using densitometry. ETOH in mitogenic media promoted formation of neurospheres by NSC, GCP, and NCP. Under control conditions, GCP attached and differentiated, NSC and NCP formed neurospheres that were significantly smaller in size than those in ETOH. Under differentiating conditions, Map2a expression increased significantly in NSC and GCP and reduced significantly in NCP, and GFAP expression reduced significantly in GCP and NCP, and Gal-C expression reduced significantly in all 3 cell types in the presence of ETOH compared to controls. This study shows that ETOH alters the cell fate of neuronal stem and progenitor cells. These alterations could contribute to the mechanism for the abnormal brain development in FASD.

  19. Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.

    Science.gov (United States)

    Abou-Antoun, Tamara J; Hale, James S; Lathia, Justin D; Dombrowski, Stephen M

    2017-04-01

    Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.

  20. Individual Assessment of Brain Tissue Changes in MS and the Effect of Focal Lesions on Short-Term Focal Atrophy Development in MS: A Voxel-Guided Morphometry Study

    Directory of Open Access Journals (Sweden)

    Jan Fox

    2016-04-01

    Full Text Available We performed voxel-guided morphometry (VGM investigating the mechanisms of brain atrophy in multiple sclerosis (MS related to focal lesions. VGM maps detect regional brain changes when comparing 2 time points on high resolution T1-weighted (T1w magnetic resonace imaging (MRI. Two T1w MR datasets from 92 relapsing-remitting MS patients obtained 12 months apart were analysed with VGM. New lesions and volume changes of focal MS lesions as well as in the surrounding tissue were identified by visual inspection on colour coded VGM maps. Lesions were dichotomized in active and inactive lesions. Active lesions, defined by either new lesions (NL (volume increase > 5% in VGM, chronic enlarging lesions (CEL (pre-existent T1w lesions with volume increase > 5%, or chronic shrinking lesions (CSL (pre-existent T1w lesions with volume reduction > 5% in VGM, were accompanied by tissue shrinkage in surrounding and/or functionally related regions. Volume loss within the corpus callosum was highly correlated with the number of lesions in its close proximity. Volume loss in the lateral geniculate nucleus was correlated with lesions along the optic radiation. VGM analysis provides strong evidence that all active lesion types (NL, CEL, and CSL contribute to brain volume reduction in the vicinity of lesions and/or in anatomically and functionally related areas of the brain.

  1. Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Janel E. Le Belle

    2014-11-01

    Full Text Available A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  2. Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells.

    Science.gov (United States)

    Kraft, Anna; Jubal, Eduardo Rosales; von Laer, Ruth; Döring, Claudia; Rocha, Adriana; Grebbin, Moyo; Zenke, Martin; Kettenmann, Helmut; Stroh, Albrecht; Momma, Stefan

    2017-03-14

    Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ) to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia. Using a newly established in vitro system we show that calcium waves induced in an astrocytic monolayer spread to neural stem and progenitor cells and increase their self-renewal as well as migratory behavior. These changes are due to an upregulation of the Notch signaling pathway. This introduces the concept of propagating astrocytic calcium waves transmitting brain injury signals over long distances. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Morphological and histochemical changes in the brain stem in case of experimental hemispheric intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    S. I. Tertishniy

    2015-10-01

    Full Text Available Aim. Investigation of the extent of morphological changes and activity of biogenic amines (according to the intensity of luminescence in the neurons of the brain stem in intracerebral hemorrhage (ICH. Methods and results. ICH was designed on 29 white rats of Vistar line by the administration of autologous blood in the cerebral hemisphere. It was revealed that increased luminescence intensity by 18.4±5.5% was registered in monoaminergic neurons in 1–6 hours after experimental ICH. After 12 hours – 1 day development of dislocation syndrome leads to mosaic focal ischemic neuronal injuries with maximum reduction in the level of catecholamines by 29.5±5.0% compared with control cases. Three–6 days after ICH on a background of selective neuronal necrosis in substantial number of neurons in the nuclei of the brainstem the level of catecholamines is significantly reduced. Conclusion. Disclosed observations reflect significant functional pathology of neurons responsible for the regulation of cardiorespiratory function and may underlie disturbances of integrative activity in the brain stem in general.

  4. Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.

    Science.gov (United States)

    Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

    2015-10-01

    Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation

  5. Optic Nerve Atrophy

    Science.gov (United States)

    ... cord (hydrocephalus) may prevent further optic nerve damage. Spectacles may be prescribed to correct refractive error. When optic atrophy is unilateral protection of the good eye is essential and wearing of protective lenses should ...

  6. Targeted activation of primitive neural stem cells in the mouse brain.

    Science.gov (United States)

    Reeve, Rachel L; Yammine, Samantha Z; DeVeale, Brian; van der Kooy, Derek

    2016-06-01

    Primitive neural stem cells (pNSCs) are the earliest NSCs to appear in the developing forebrain. They persist into the adult forebrain where they can generate all cells in the neural lineage and therefore hold great potential for brain regeneration. Thus, pNSCs are an ideal population to target to promote endogenous NSC activation. pNSCs can be isolated from the periventricular region as leukaemia inhibitory factor-responsive cells, and comprise a rare population in the adult mouse brain. We hypothesized that the pup periventricular region gives rise to more clonal pNSC-derived neurospheres but that pup-derived pNSCs are otherwise comparable to adult-derived pNSCs, and can be used to identify selective markers and activators of endogenous pNSCs. We tested the self-renewal ability, differentiation capacity and gene expression profile of pup-derived pNSCs and found them each to be comparable to adult-derived pNSCs, including being GFAP(-) , nestin(mid) , Oct4(+) . Next, we used pup pNSCs to test pharmacological compounds to activate pNSCs to promote endogenous brain repair. We hypothesized that pNSCs could be activated by targeting the cell surface proteins C-Kit and ErbB2, which were enriched in pNSCs relative to definitive NSCs (dNSCs) in an in vitro screen. C-Kit and ErbB2 signalling inhibition had distinct effects on pNSCs and dNSCs in vitro, and when infused directly into the adult brain in vivo. Targeted activation of pNSCs with C-Kit and ErbB2 modulation is a valuable strategy to activate the earliest cell in the neural lineage to contribute to endogenous brain regeneration. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  7. Physical weight loading induces expression of tryptophan hydroxylase 2 in the brain stem.

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    Joon W Shim

    Full Text Available Sustaining brain serotonin is essential in mental health. Physical activities can attenuate mental problems by enhancing serotonin signaling. However, such activity is not always possible in disabled individuals or patients with dementia. Knee loading, a form of physical activity, has been found to mimic effects of voluntary exercise. Focusing on serotonergic signaling, we addressed a question: Does local mechanical loading to the skeleton elevate expression of tryptophan hydroxylase 2 (tph2 that is a rate-limiting enzyme for brain serotonin? A 5 min knee loading was applied to mice using 1 N force at 5 Hz for 1,500 cycles. A 5-min treadmill running was used as an exercise (positive control, and a 90-min tail suspension was used as a stress (negative control. Expression of tph2 was determined 30 min - 2 h in three brain regions --frontal cortex (FC, ventromedial hypothalamus (VMH, and brain stem (BS. We demonstrated for the first time that knee loading and treadmill exercise upregulated the mRNA level of tph2 in the BS, while tail suspension downregulated it. The protein level of tph2 in the BS was also upregulated by knee loading and downregulated by tail suspension. Furthermore, the downregulation of tph2 mRNA by tail suspension can be partially suppressed by pre-application of knee loading. The expression of tph2 in the FC and VMH was not significantly altered with knee loading. In this study we provided evidence that peripheral mechanical loading can activate central tph2 expression, suggesting that physical cues may mediate tph2-cathalyzed serotonergic signaling in the brain.

  8. Clinical application of human adipose tissue-derived mesenchymal stem cells in progressive hemifacial atrophy (Parry-Romberg disease) with microfat grafting techniques using 3-dimensional computed tomography and 3-dimensional camera.

    Science.gov (United States)

    Koh, Kyung Suk; Oh, Tae Suk; Kim, Hoon; Chung, In Wook; Lee, Kang Woo; Lee, Hyo Bo; Park, Eun Jung; Jung, Jae Seob; Shin, Il Seob; Ra, Jeong Chan; Choi, Jong Woo

    2012-09-01

    Parry-Romberg disease is a rare condition that results in progressive hemifacial atrophy, involving the skin, dermis, subcutaneous fat, muscle, and, finally, cartilage and bone. Patients have been treated with dermofat or fat grafts or by microvascular free flap transfer. We hypothesized that adipose-derived stem cells (ASCs) may improve the results of microfat grafting through enhancing angiogenesis. We evaluated the utility of ASC in microfat grafting of patients with Parry-Romberg disease by measuring the change in the hemifacial volumes after injection of ASCs with microfat grafts or microfat grafts alone. In April 2008, this investigation was approved by the Korean Food and Drug Administration and the institutional review board of the Asan Medical Center (Seoul, Korea) that monitor investigator-initiated trials. Between May 2008 and January 2009, 10 volunteers with Parry-Romberg disease (5 men and 5 women; mean age, 28 y) were recruited; 5 received ASC and microfat grafts and 5 received microfat grafts only. The mean follow-up period was 15 months. Adipose-derived stem cells were obtained from abdominal fat by liposuction and were cultured for 2 weeks. On day 14, patients were injected with fat grafts alone or plus (in the test group) 1 × 10 ASCs. Patients were evaluated postoperatively using a 3-dimensional camera and 3-dimensional CT scans, and grafted fat volumes were objectively calculated. Successful outcomes were evident in all 5 patients receiving microfat grafts and ASCs, and the survival of grafted fat was better than in patients receiving microfat grafts alone. Before surgery, the mean difference between ipsilateral and contralateral hemiface volume in patients receiving microfat grafts and ASCs was 21.71 mL decreasing to 4.47 mL after surgery. Overall resorption in this ASC group was 20.59%. The mean preoperative difference in hemiface volume in those receiving microfat grafts alone was 8.32 mL decreasing to 3.89 mL after surgery. Overall

  9. Exposure to 835 MHz radiofrequency electromagnetic field induces autophagy in hippocampus but not in brain stem of mice.

    Science.gov (United States)

    Kim, Ju Hwan; Yu, Da-Hyeon; Kim, Hyo-Jeong; Huh, Yang Hoon; Cho, Seong-Wan; Lee, Jin-Koo; Kim, Hyung-Gun; Kim, Hak Rim

    2017-01-01

    The exploding popularity of mobile phones and their close proximity to the brain when in use has raised public concern regarding possible adverse effects from exposure to radiofrequency electromagnetic fields (RF-EMF) on the central nervous system. Numerous studies have suggested that RF-EMF emitted by mobile phones can influence neuronal functions in the brain. Currently, there is still very limited information on what biological mechanisms influence neuronal cells of the brain. In the present study, we explored whether autophagy is triggered in the hippocampus or brain stem after RF-EMF exposure. C57BL/6 mice were exposed to 835 MHz RF-EMF with specific absorption rates (SAR) of 4.0 W/kg for 12 weeks; afterward, the hippocampus and brain stem of mice were dissected and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that several autophagic genes, which play key roles in autophagy regulation, were significantly upregulated only in the hippocampus and not in the brain stem. Expression levels of LC3B-II protein and p62, crucial autophagic regulatory proteins, were significantly changed only in the hippocampus. In parallel, transmission electron microscopy (TEM) revealed an increase in the number of autophagosomes and autolysosomes in the hippocampal neurons of RF-EMF-exposed mice. The present study revealed that autophagy was induced in the hippocampus, not in the brain stem, in 835 MHz RF-EMF with an SAR of 4.0 W/kg for 12 weeks. These results could suggest that among the various adaptation processes to the RF-EMF exposure environment, autophagic degradation is one possible mechanism in specific brain regions.

  10. Differentiation and characterization of human pluripotent stem cell-derived brain microvascular endothelial cells.

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    Stebbins, Matthew J; Wilson, Hannah K; Canfield, Scott G; Qian, Tongcheng; Palecek, Sean P; Shusta, Eric V

    2016-05-15

    The blood-brain barrier (BBB) is a critical component of the central nervous system (CNS) that regulates the flux of material between the blood and the brain. Because of its barrier properties, the BBB creates a bottleneck to CNS drug delivery. Human in vitro BBB models offer a potential tool to screen pharmaceutical libraries for CNS penetration as well as for BBB modulators in development and disease, yet primary and immortalized models respectively lack scalability and robust phenotypes. Recently, in vitro BBB models derived from human pluripotent stem cells (hPSCs) have helped overcome these challenges by providing a scalable and renewable source of human brain microvascular endothelial cells (BMECs). We have demonstrated that hPSC-derived BMECs exhibit robust structural and functional characteristics reminiscent of the in vivo BBB. Here, we provide a detailed description of the methods required to differentiate and functionally characterize hPSC-derived BMECs to facilitate their widespread use in downstream applications. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

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    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  12. Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury.

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    Drommelschmidt, Karla; Serdar, Meray; Bendix, Ivo; Herz, Josephine; Bertling, Frederik; Prager, Sebastian; Keller, Matthias; Ludwig, Anna-Kristin; Duhan, Vikas; Radtke, Stefan; de Miroschedji, Kyra; Horn, Peter A; van de Looij, Yohan; Giebel, Bernd; Felderhoff-Müser, Ursula

    2017-02-01

    Preterm brain injury is a major cause of disability in later life, and may result in motor, cognitive and behavioural impairment for which no treatment is currently available. The aetiology is considered as multifactorial, and one underlying key player is inflammation leading to white and grey matter injury. Extracellular vesicles secreted by mesenchymal stem/stromal cells (MSC-EVs) have shown therapeutic potential in regenerative medicine. Here, we investigated the effects of MSC-EV treatment on brain microstructure and maturation, inflammatory processes and long-time outcome in a rodent model of inflammation-induced brain injury. 3-Day-old Wistar rats (P3) were intraperitoneally injected with 0.25mg/kg lipopolysaccharide or saline and treated with two repetitive doses of 1×10 8 cell equivalents of MSC-EVs per kg bodyweight. Cellular degeneration and reactive gliosis at P5 and myelination at P11 were evaluated by immunohistochemistry and western blot. Long-term cognitive and motor function was assessed by behavioural testing. Diffusion tensor imaging at P125 evaluated long-term microstructural white matter alterations. MSC-EV treatment significantly ameliorated inflammation-induced neuronal cellular degeneration reduced microgliosis and prevented reactive astrogliosis. Short-term myelination deficits and long-term microstructural abnormalities of the white matter were restored by MSC-EV administration. Morphological effects of MSC-EV treatment resulted in improved long-lasting cognitive functions INTERPRETATION: MSC-EVs ameliorate inflammation-induced cellular damage in a rat model of preterm brain injury. MSC-EVs may serve as a novel therapeutic option by prevention of neuronal cell death, restoration of white matter microstructure, reduction of gliosis and long-term functional improvement. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Exogenous stem cells pioneer a biobridge to the advantage of host brain cells following stroke: New insights for clinical applications

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    Marci G Crowley

    2017-01-01

    Full Text Available Stroke continues to maintain its status as one of the top causes of mortality within the United States. Currently, the only Food and Drug Administration (FDA-approved drug in place for stroke patients, tissue plasminogen activator (tPA, has a rigid therapeutic window, closing at approximately 4.5 h after stroke onset. Due to this short time frame and other restrictions, such as any condition that increases a patient's risk for hemorrhaging, it has been predicted that <5% of ischemic stroke patients benefit from tPA. Given that rehabilitation therapy remains the only other option for stroke victims, there is a clear unmet clinical need for treatment available for the remaining 95%. While still considered an experimental treatment, the utilization of stem cell therapies for stroke holds consistent promise. Copious preclinical studies report the capacity for transplanted stem cells to rescue the brain parenchyma surrounding the stroke-induced infarct core. At present, the exact mechanisms in which stem cells contribute a robust therapeutic benefit remains unclear. Following stem cell administration, researchers have observed cell replacement, an increase in growth factors, and a reduction in inflammation. With a deeper understanding of the precise mechanism of stem cells, these therapies can be optimized in the clinic to afford the greatest therapeutic benefit. Recent studies have depicted a unique method of endogenous stem cell activation as a result of stem cell therapy. In both traumatic brain injury and stroke models, transplanted mesenchymal stromal cells (MSCs facilitated a pathway between the neurogenic niches of the brain and the damaged area through extracellular matrix remodeling. The biobridge pioneered by the MSCs was utilized by the endogenous stem cells, and these cells were able to travel to the damaged areas distal to the neurogenic niches, a feat unachievable without prior remodeling. These studies broaden our understanding of stem

  14. Severe Spastic Trismus without Generalized Spasticity after Unilateral Brain Stem Stroke

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    Seo, Jong-Hyun; Kang, Si Hyun; Seo, Kyung-Mook; Seok, Ju Won

    2012-01-01

    A 62-year-old female patient diagnosed with left brain stem stroke 2 months ago was admitted to our clinic for rehabilitation. She had no generalized spasticity on both extremities, but could open her mouth only approximately 2 mm between her upper and lower teeth due to severe trismus. On needle electromyography, the left masseter muscle showed paradoxically increased muscle activity during mouth opening. We injected 50 units of type A botulinum toxin (Botox®) into the left masseter muscle, and 20 units into the left temporalis muscle with guidance of ultrasonography. The interincisal distance increased to 8 mm on the 3rd day after injection, and 9 mm on the 4th day. One month later, the interincisal distance increased to 14 mm. The increased interincisal distance was maintained for 13 months after injection, and the quality of hygienic care and compliance of oral stimulation therapy also improved. PMID:22506250

  15. Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity

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    Quinn, K. J.; Didier, A. J.; Baker, J. F.; Peterson, B. W.

    1998-01-01

    A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

  16. Overlap of saccadic and pursuit eye movement systems in the brain stem reticular formation.

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    Yan, Y J; Cui, D M; Lynch, J C

    2001-12-01

    Recent physiological studies have suggested that there are several sites of interaction between the neural pathways that control saccadic eye movements and those that control visual pursuit movements. To address the question of saccade/pursuit interaction from a neuroanatomical point of view, we have studied the connections from the smooth and saccadic eye movement subregions of the frontal eye field (FEFsem and FEFsac, respectively) to the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) in four Cebus apella monkeys. The riMLF has traditionally been considered to be a premotor center for vertical saccadic eye movements on the basis of single neuron recording experiments, microstimulation experiments, and surgical or chemical lesion experiments. We localized the functional subregions of the FEF with the use of low-threshold (smooth pursuit eye movements and supports the hypothesis that there is interaction between the saccadic and pursuit subsystems at the brain stem level.

  17. Brain stem death as the vital determinant for resumption of spontaneous circulation after cardiac arrest in rats.

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    Alice Y W Chang

    Full Text Available BACKGROUND: Spontaneous circulation returns to less than half of adult cardiac arrest victims who received in-hospital resuscitation. One clue for this disheartening outcome arises from the prognosis that asystole invariably takes place, after a time lag, on diagnosis of brain stem death. The designation of brain stem death as the point of no return further suggests that permanent impairment of the brain stem cardiovascular regulatory machinery precedes death. It follows that a crucial determinant for successful revival of an arrested heart is that spontaneous circulation must resume before brain stem death commences. Here, we evaluated the hypothesis that maintained functional integrity of the rostral ventrolateral medulla (RVLM, a neural substrate that is intimately related to brain stem death and central circulatory regulation, holds the key to the vital time-window between cardiac arrest and resumption of spontaneous circulation. METHODOLOGY/PRINCIPAL FINDINGS: An animal model of brain stem death employing the pesticide mevinphos as the experimental insult in Sprague-Dawley rats was used. Intravenous administration of lethal doses of mevinphos elicited an abrupt cardiac arrest, accompanied by elevated systemic arterial pressure and anoxia, augmented neuronal excitability and enhanced microvascular perfusion in RVLM. This period represents the vital time-window between cardiac arrest and resumption of spontaneous circulation in our experimental model. Animals with restored spontaneous circulation exhibited maintained neuronal functionality in RVLM beyond this critical time-window, alongside resumption of baseline tissue oxygen and enhancement of local blood flow. Intriguingly, animals that subsequently died manifested sustained anoxia, diminished local blood flow, depressed mitochondrial electron transport activities and reduced ATP production, leading to necrotic cell death in RVLM. That amelioration of mitochondrial dysfunction and

  18. Human Adipose Tissue-Derived Mesenchymal Stem Cells Target Brain Tumor-Initiating Cells.

    Science.gov (United States)

    Choi, Seung Ah; Lee, Ji Yeoun; Kwon, Sung Eun; Wang, Kyu-Chang; Phi, Ji Hoon; Choi, Jung Won; Jin, Xiong; Lim, Ja Yun; Kim, Hyunggee; Kim, Seung-Ki

    2015-01-01

    In neuro-oncology, the biology of neural stem cells (NSCs) has been pursued in two ways: as tumor-initiating cells (TICs) and as a potential cell-based vehicle for gene therapy. NSCs as well as mesenchymal stem cells (MSCs) have been reported to possess tumor tropism capacities. However, there is little data on the migratory capacity of MSCs toward brain tumor-initiating cells (BTICs). This study focuses on the ability of human adipose tissue derived MSCs (hAT-MSCs) to target BTICs and their crosstalk in the microenvironment. BTICs were isolated from three different types of brain tumors. The migration capacities of hAT-MSCs toward BTICs were examined using an in vitro migration assay and in vivo bioluminescence imaging analysis. To investigate the crosstalk between hAT-MSCs and BTICs, we analyzed the mRNA expression patterns of cyto-chemokine receptors by RT-qPCR and the protein level of their ligands in co-cultured medium. The candidate cyto-chemokine receptors were selectively inhibited using siRNAs. Both in vitro and in vivo experiments showed that hAT-MSCs possess migratory abilities to target BTICs isolated from medulloblastoma, atypical teratoid/rhabdoid tumors (AT/RT) and glioblastoma. Different types of cyto-chemokines are involved in the crosstalk between hAT-MSCs and BTICs (medulloblastoma and AT/RT: CXCR4/SDF-1, CCR5/RANTES, IL6R/IL-6 and IL8R/IL8; glioblastoma: CXCR4/SDF-1, IL6R/IL-6, IL8R/IL-8 and IGF1R/IGF-1). Our findings demonstrated the migratory ability of hAT-MSCs for BTICs, implying the potential use of MSCs as a delivery vehicle for gene therapy. This study also confirmed the expression of hAT-MSCs cytokine receptors and the BTIC ligands that play roles in their crosstalk.

  19. Bioenergetics failure and oxidative stress in brain stem mediates cardiovascular collapse associated with fatal methamphetamine intoxication.

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    Faith C H Li

    Full Text Available BACKGROUND: Whereas sudden death, most often associated with cardiovascular collapse, occurs in abusers of the psychostimulant methamphetamine (METH, the underlying mechanism is much less understood. The demonstration that successful resuscitation of an arrested heart depends on maintained functionality of the rostral ventrolateral medulla (RVLM, which is responsible for the maintenance of stable blood pressure, suggests that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse. We tested the hypothesis that cessation of brain stem cardiovascular regulation because of a loss of functionality in RVLM mediated by bioenergetics failure and oxidative stress underlies the cardiovascular collapse elicited by lethal doses of METH. METHODOLOGY/PRINCIPAL FINDINGS: Survival rate, cardiovascular responses and biochemical or morphological changes in RVLM induced by intravenous administration of METH in Sprague-Dawley rats were investigated. High doses of METH induced significant mortality within 20 min that paralleled concomitant the collapse of arterial pressure or heart rate and loss of functionality in RVLM. There were concurrent increases in the concentration of METH in serum and ventrolateral medulla, along with tissue anoxia, cessation of microvascular perfusion and necrotic cell death in RVLM. Furthermore, mitochondrial respiratory chain enzyme activity or electron transport capacity and ATP production in RVLM were reduced, and mitochondria-derived superoxide anion level was augmented. All those detrimental physiological and biochemical events were reversed on microinjection into RVLM of a mobile electron carrier in the mitochondrial respiratory chain, coenzyme Q10; a mitochondria-targeted antioxidant and superoxide anion scavenger, Mito-TEMPO; or an oxidative stress-induced necrotic cell death inhibitor, IM-54. CONCLUSION: We conclude that sustained anoxia and cessation of local blood flow

  20. Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain.

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    Amort, Thomas; Rieder, Dietmar; Wille, Alexandra; Khokhlova-Cubberley, Daria; Riml, Christian; Trixl, Lukas; Jia, Xi-Yu; Micura, Ronald; Lusser, Alexandra

    2017-01-05

    Recent work has identified and mapped a range of posttranscriptional modifications in mRNA, including methylation of the N6 and N1 positions in adenine, pseudouridylation, and methylation of carbon 5 in cytosine (m5C). However, knowledge about the prevalence and transcriptome-wide distribution of m5C is still extremely limited; thus, studies in different cell types, tissues, and organisms are needed to gain insight into possible functions of this modification and implications for other regulatory processes. We have carried out an unbiased global analysis of m5C in total and nuclear poly(A) RNA of mouse embryonic stem cells and murine brain. We show that there are intriguing differences in these samples and cell compartments with respect to the degree of methylation, functional classification of methylated transcripts, and position bias within the transcript. Specifically, we observe a pronounced accumulation of m5C sites in the vicinity of the translational start codon, depletion in coding sequences, and mixed patterns of enrichment in the 3' UTR. Degree and pattern of methylation distinguish transcripts modified in both embryonic stem cells and brain from those methylated in either one of the samples. We also analyze potential correlations between m5C and micro RNA target sites, binding sites of RNA binding proteins, and N6-methyladenosine. Our study presents the first comprehensive picture of cytosine methylation in the epitranscriptome of pluripotent and differentiated stages in the mouse. These data provide an invaluable resource for future studies of function and biological significance of m5C in mRNA in mammals.

  1. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

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    Erica L. McGrath

    2017-03-01

    Full Text Available Zika virus (ZIKV infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7, to infect primary human neural stem cells (hNSCs originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

  2. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection.

    Science.gov (United States)

    McGrath, Erica L; Rossi, Shannan L; Gao, Junling; Widen, Steven G; Grant, Auston C; Dunn, Tiffany J; Azar, Sasha R; Roundy, Christopher M; Xiong, Ying; Prusak, Deborah J; Loucas, Bradford D; Wood, Thomas G; Yu, Yongjia; Fernández-Salas, Ildefonso; Weaver, Scott C; Vasilakis, Nikos; Wu, Ping

    2017-03-14

    Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Recovery from a possible cytomegalovirus meningoencephalitis-induced apparent brain stem death in an immunocompetent man: a case report.

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    Rahardjo, Theresia Monica; Maskoen, Tinni Trihartini; Redjeki, Ike Sri

    2016-08-26

    Recovery from cytomegalovirus meningoencephalitis with brain stem death in an immunocompetent patient is almost impossible. We present a remarkable recovery from a possible cytomegalovirus infection in an immunocompetent man who had severe neurological syndromes, suggesting brain stem death complicated by pneumonia and pleural effusion. A 19-year-old Asian man presented at our hospital's emergency department with reduced consciousness and seizures following high fever, headache, confusion, and vomitus within a week before arrival. He was intubated and sent to our intensive care unit. He had nuchal rigidity and tetraparesis with accentuated tendon reflexes. Electroencephalography findings suggested an acute structural lesion at his right temporal area or an epileptic state. A cerebral spinal fluid examination suggested viral infection. A computed tomography scan was normal at the early stage of disease. Immunoglobulin M, immunoglobulin G anti-herpes simplex virus, and immunoglobulin M anti-cytomegalovirus were negative. However, immunoglobulin G anti-cytomegalovirus was positive, which supported a diagnosis of cytomegalovirus meningoencephalitis. His clinical condition deteriorated, spontaneous respiration disappeared, cranial reflexes became negative, and brain stem death was suspected. Therapy included antivirals, corticosteroids, antibiotics, anticonvulsant, antipyretics, antifungal agents, and a vasopressor to maintain hemodynamic stability. After 1 month, he showed a vague response to painful stimuli at his supraorbital nerve and respiration started to appear the following week. After pneumonia and pleural effusion were resolved, he was weaned from the ventilator and moved from the intensive care unit on day 90. This case highlights several important issues that should be considered. First, the diagnosis of brain stem death must be confirmed with caution even if there are negative results of brain stem death test for a long period. Second, cytomegalovirus

  4. Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers.

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    Farace, Paolo; Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

    2014-01-06

    Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step-and-shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose < 45 Gy to spinal cord and < 50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5 ± 2.2 Gy and 36.7 ± 14.0 Gy), without significant changes on the other OARs. A marked difference (-15.9 ± 1.9 Gy and -10.1 ± 5.7 Gy) was obtained at the expense of a small difference (-1.3% ± 0.9%) from initial PTV195% coverage (96.6% ± 0.9%). Similar difference (-15.7 ± 2.2 Gy and -10.2 ± 6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (-0.3% ± 0.3% from the initial 98.3% ± 0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer.

  5. Progesterone promotes neuronal differentiation of human umbilical cord mesenchymal stem cells in culture conditions that mimic the brain microenvironment★

    Science.gov (United States)

    Wang, Xianying; Wu, Honghai; Xue, Gai; Hou, Yanning

    2012-01-01

    In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vaginal delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats (to mimic the brain microenvironment). Immunocytochemical analysis demonstrated that the cells differentiated into neuron-like cells. To evaluate the effects of progesterone as a neurosteroid on the neuronal differentiation of human umbilical cord mesenchymal stem cells, we cultured the cells in medium containing progesterone (0.1, 1, 10 μM) in addition to brain tissue extracts. Reverse transcription-PCR and flow cytometric analysis of neuron specific enolase-positive cells revealed that the percentages of these cells increased significantly following progesterone treatment, with the optimal progesterone concentration for neuron-like differentiation being 1 μM. These results suggest that progesterone can enhance the neuronal differentiation of human umbilical cord mesenchymal stem cells in culture medium containing brain tissue extracts to mimic the brain microenvironment. PMID:25624820

  6. [Deep-seated (corpus callosum, intraventricular, basal ganglia and insula) and brain stem cavernous angiomas. Experience in Brazil].

    Science.gov (United States)

    Alves de Sousa, A

    2007-06-01

    With a review of the literature, we report our experience with surgical treatment of deep-seated cavernomas (intraventricular, of the corpus callosum, the capsula interna, the insula and the brain stem). Outcome was good in all nine patients after surgery for deep-seated brain cavernomas. There we also 13 cases of the brain stem cavernomas treated surgically. Of them, nine patients were stabilized or improved, one patient worsened, one patient died and two were lost to follow-up. Whatever the location, surgery should only concern symptomatic or hemorrhagic lesions close to the pia-matter or the ependyma as well as those covered by a thin layer of parenchyma. Neuronavigation and microsurgical procedures are essential in the treatment of deep-seated cavernomas.

  7. 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.)

  8. High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

    Energy Technology Data Exchange (ETDEWEB)

    Gizewski, Elke R. [Medical University Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Maderwald, Stefan [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Linn, Jennifer; Bochmann, Katja [LMU Munich, Department of Neuroradiology, Munich (Germany); Dassinger, Benjamin [Medical University Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Justus-Liebig-University Giessen, Department of Neuroradiology, Giessen (Germany); Forsting, Michael [University Hospital, University Duisburg-Essen, Departments of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Ladd, Mark E. [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital, University Duisburg-Essen, Departments of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany)

    2014-03-15

    The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures. (orig.)

  9. Gold nanoparticle-cell labeling methodology for tracking stem cells within the brain

    Science.gov (United States)

    Betzer, Oshra; Meir, Rinat; Motiei, Menachem; Yadid, Gal; Popovtzer, Rachela

    2017-02-01

    Cell therapy provides a promising approach for diseases and injuries that conventional therapies cannot cure effectively. Mesenchymal stem cells (MSCs) can be used as effective targeted therapy, as they exhibit homing capabilities to sites of injury and inflammation, exert anti-inflammatory effects, and can differentiate in order to regenerate damaged tissue. Despite the potential efficacy of cell therapy, applying cell-based therapy in clinical practice is very challenging; there is a need to uncover the mystery regarding the fate of the transplanted cells. Therefore, in this study, we developed a method for longitudinal and quantitative in vivo cell tracking, based on the superior visualization abilities of classical X-ray computed tomography (CT), and combined with gold nanoparticles as labeling agents. We applied this technique for non-invasive imaging of MSCs transplanted in a rat model for depression, a highly prevalent and disabling neuropsychiatric disorder lacking effective treatment. Our results, which demonstrate that cell migration could be detected as early as 24 hours and up to one month post-transplantation, revealed that MSCs specifically navigated and homed to distinct depression related brain regions. This research further reveals that cell therapy is a beneficial approach for treating neuropsychiatric disorders; Behavioral manifestations of core symptoms of depressive behavior, were significantly attenuated following treatment. We expect This CT-based technique to lead to a significant enhancement in cellular therapy both for basic research and clinical applications of brain pathologies.

  10. Entracking as a Brain Stem Code for Pitch: The Butte Hypothesis.

    Science.gov (United States)

    Joris, Philip X

    2016-01-01

    The basic nature of pitch is much debated. A robust code for pitch exists in the auditory nerve in the form of an across-fiber pooled interspike interval (ISI) distribution, which resembles the stimulus autocorrelation. An unsolved question is how this representation can be "read out" by the brain. A new view is proposed in which a known brain-stem property plays a key role in the coding of periodicity, which I refer to as "entracking", a contraction of "entrained phase-locking". It is proposed that a scalar rather than vector code of periodicity exists by virtue of coincidence detectors that code the dominant ISI directly into spike rate through entracking. Perfect entracking means that a neuron fires one spike per stimulus-waveform repetition period, so that firing rate equals the repetition frequency. Key properties are invariance with SPL and generalization across stimuli. The main limitation in this code is the upper limit of firing (~ 500 Hz). It is proposed that entracking provides a periodicity tag which is superimposed on a tonotopic analysis: at low SPLs and fundamental frequencies > 500 Hz, a spectral or place mechanism codes for pitch. With increasing SPL the place code degrades but entracking improves and first occurs in neurons with low thresholds for the spectral components present. The prediction is that populations of entracking neurons, extended across characteristic frequency, form plateaus ("buttes") of firing rate tied to periodicity.

  11. Mesenchymal Stem Cells Attenuate Radiation-Induced Brain Injury by Inhibiting Microglia Pyroptosis

    Directory of Open Access Journals (Sweden)

    Huan Liao

    2017-01-01

    Full Text Available Radiation-induced brain injury (RI commonly occurs in patients who received head and neck radiotherapy. However, the mechanism of RI remains unclear. We aimed to evaluate whether pyroptosis was involved in RI and the impact of mesenchymal stem cells (MSCs on it. BALB/c male mice (6–8 weeks were cranially irradiated (15 Gy, and MSCs were transplanted into the bilateral cortex 2 days later; then mice were sacrificed 1 month later. Meanwhile, irradiated BV-2 microglia cells (10 Gy were cocultured with MSCs for 24 hours. We observed that irradiated mice brains presented NLRP3 and caspase-1 activation. RT-PCR then indicated that it mainly occurred in microglia cells but not in neurons. Further, irradiated BV-2 cells showed pyroptosis and increased production of IL-18 and IL-1β. RT-PCR also demonstrated an increased expression of several inflammasome genes in irradiated BV-2 cells, including NLRP3 and AIM2. Particularly, NLRP3 was activated. Knockdown of NLRP3 resulted in decreased LDH release. Noteworthily, in vivo, MSCs transplantation alleviated radiation-induced NLRP3 and caspase-1 activation. Moreover, in vitro, MSCs could decrease caspase-1 dependent pyroptosis, NLRP3 inflammasome activation, and ROS production induced by radiation. Thus, our findings proved that microglia pyroptosis occurred in RI. MSCs may act as a potent therapeutic tool in attenuating pyroptosis.

  12. Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons

    Science.gov (United States)

    Brown, Maile R.; El-Hassar, Lynda; Zhang, Yalan; Alvaro, Giuseppe; Large, Charles H.

    2016-01-01

    Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express “high threshold” voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3.1 channels. Using Chinese hamster ovary cells stably expressing rat Kv3.1 channels, we found that lower concentrations of these compounds shift the voltage of activation of Kv3.1 currents toward negative potentials, increasing currents evoked by depolarization from typical neuronal resting potentials. Single-channel recordings also showed that AUT1 shifted the open probability of Kv3.1 to more negative potentials. Higher concentrations of AUT2 also shifted inactivation to negative potentials. The effects of lower and higher concentrations could be mimicked in numerical simulations by increasing rates of activation and inactivation respectively, with no change in intrinsic voltage dependence. In brain slice recordings of mouse MNTB neurons, both AUT1 and AUT2 modulated firing rate at high rates of stimulation, a result predicted by numerical simulations. Our results suggest that pharmaceutical modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability and has the potential for therapeutic benefit in the treatment of hearing disorders. PMID:27052580

  13. 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....

  14. Imaging of olfactory bulb and gray matter volumes in brain areas associated with olfactory function in patients with Parkinson's disease and multiple system atrophy.

    Science.gov (United States)

    Chen, Shun; Tan, Hong-yu; Wu, Zhuo-hua; Sun, Chong-peng; He, Jian-xun; Li, Xin-chun; Shao, Ming

    2014-03-01

    We explored if magnetic resonance imaging sequences might aid in the clinical differential diagnosis of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA). We measured the volumes of the olfactory bulb, the olfactory tract, and olfaction-associated cortical gray matter in 20 IPD patients, 14 MSA patients, and 12 normal subjects, using high-resolution magnetic resonance imaging sequences in combination with voxel-based statistical analysis. We found that, compared to normal subjects and MSA patients, the volumes of the olfactory bulb and tract were significantly reduced in IPD patients. The gray matter volume of IPD patients decreased in the following order: the olfactory area to the right of the piriform cortex, the right amygdala, the left entorhinal cortex, and the left occipital lobe. Further, the total olfactory bulb volume of IPD patients was associated with the duration of disease. The entorhinal cortical gray matter volume was negatively associated with the UPDRS III score. Structural volumes measured by high-resolution magnetic resonance imaging may potentially be used for differential diagnosis of IPD from MSA. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Bilateral cortical atrophy after severe brain trauma and extradural homatoma Atrofia cortical bilateral após traumatismo cranioencefálico grave e hematoma extradural

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Louzada

    2007-12-01

    Full Text Available We report the case of a severe head injured 43-year old male patient with a large extradural hematoma, Glasgow Coma Scale 3 and dilated fixed pupils. Patient was promptly submitted to surgical evacuation of the lesion, but remained in persistent vegetative state in the post-operative time. Head computed tomography scans performed before surgery, and at early and late post-operative periods comparatively revealed extreme bilateral cortical atrophy. Late consequences of severe head trauma drastically affect the prognosis of patients, being its prevention, and neuroprotection against secondary injury still a therapeutical challenge for neurosurgeons.Relatamos o caso de um paciente de 43 anos, com traumatismo cranioencefálico grave, com grande hematoma extradural, Escala de Coma de Glasgow 3 e pupilas fixas e dilatadas. O paciente foi prontamente submetido à evacuação cirúrgica da lesão mas permaneceu em estado vegetativo persistente no período pós-operatório. As TC de crânio realizadas antes da cirurgia e nos períodos pós-operatórios precoce e tardio revelaram comparativamente extrema atrofia cerebral bilateral. As conseqüências tardias do traumatismo craniano grave afetam drasticamente o prognóstico dos pacientes, sendo sua prevenção, e a neuroproteção contra a injúria secundária ainda um desafio terapêutico para os neurocirurgiões.

  16. Imaging of olfactory bulb and gray matter volumes in brain areas associated with olfactory function in patients with Parkinson's disease and multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shun, E-mail: shchen_2013@163.com [Department of Neurology, The First Affiliated Hospital of Guangzhou Medical College (China); Tan, Hong-yu, E-mail: honhyutan@21cn.com [Department of Neurology, The First Affiliated Hospital of Guangzhou Medical College (China); Wu, Zhuo-hua, E-mail: zhh88@126.com [Department of Neurology, The First Affiliated Hospital of Guangzhou Medical College (China); Sun, Chong-peng, E-mail: Suncp2002@gmail.com [Imaging Center, The First Affiliated Hospital of Guangzhou Medical College (China); He, Jian-xun, E-mail: xundog@163.com [Imaging Center, The First Affiliated Hospital of Guangzhou Medical College (China); Li, Xin-chun, E-mail: xinchunli@163.com [Imaging Center, The First Affiliated Hospital of Guangzhou Medical College (China); Shao, Ming, E-mail: yimshao@126.com [Department of Neurology, The First Affiliated Hospital of Guangzhou Medical College (China)

    2014-03-15

    We explored if magnetic resonance imaging sequences might aid in the clinical differential diagnosis of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA). We measured the volumes of the olfactory bulb, the olfactory tract, and olfaction-associated cortical gray matter in 20 IPD patients, 14 MSA patients, and 12 normal subjects, using high-resolution magnetic resonance imaging sequences in combination with voxel-based statistical analysis. We found that, compared to normal subjects and MSA patients, the volumes of the olfactory bulb and tract were significantly reduced in IPD patients. The gray matter volume of IPD patients decreased in the following order: the olfactory area to the right of the piriform cortex, the right amygdala, the left entorhinal cortex, and the left occipital lobe. Further, the total olfactory bulb volume of IPD patients was associated with the duration of disease. The entorhinal cortical gray matter volume was negatively associated with the UPDRS III score. Conclusion: Structural volumes measured by high-resolution magnetic resonance imaging may potentially be used for differential diagnosis of IPD from MSA.

  17. The Pattern of Brain Amyloid Load in Posterior Cortical Atrophy Using 18F-AV45: Is Amyloid the Principal Actor in the Disease

    Directory of Open Access Journals (Sweden)

    Emilie Beaufils

    2014-11-01

    Full Text Available Background: Posterior cortical atrophy (PCA is characterized by progressive higher-order visuoperceptual dysfunction and praxis declines. This syndrome is related to a number of underlying diseases, including, in most cases, Alzheimer's disease (AD. The aim of this study was to compare the amyloid load with 18F-AV45 positron emission tomography (PET between PCA and AD subjects. Methods: We performed 18F-AV45 PET, cerebrospinal fluid (CSF biomarker analysis and a neuropsychological assessment in 11 PCA patients and 12 AD patients. Results: The global and regional 18F-AV45 uptake was similar in the PCA and AD groups. No significant correlation was observed between global 18F-AV45 uptake and CSF biomarkers or between regional 18F-AV45 uptake and cognitive and affective symptoms. Conclusion: This 18F-AV45 PET amyloid imaging study showed no specific regional pattern of cortical 18F-AV45 binding in PCA patients. These results confirm that a distinct clinical phenotype in amnestic AD and PCA is not related to amyloid distribution.

  18. Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

    Science.gov (United States)

    Tornero, Daniel; Tsupykov, Oleg; Granmo, Marcus; Rodriguez, Cristina; Grønning-Hansen, Marita; Thelin, Jonas; Smozhanik, Ekaterina; Laterza, Cecilia; Wattananit, Somsak; Ge, Ruimin; Tatarishvili, Jemal; Grealish, Shane; Brüstle, Oliver; Skibo, Galina; Parmar, Malin; Schouenborg, Jens; Lindvall, Olle; Kokaia, Zaal

    2017-03-01

    Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone.

    Science.gov (United States)

    Domenichini, Florence; Terrié, Elodie; Arnault, Patricia; Harnois, Thomas; Magaud, Christophe; Bois, Patrick; Constantin, Bruno; Coronas, Valérie

    2018-01-23

    The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult NSC. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in NSC whose cellular activities are continuously adapted to physiological signals from the microenvironment. By Reverse Transcription Polymerase Chain Reaction (RT-PCR), Western blotting and immunocytochemistry experiments, we demonstrate that SVZ cells express molecular actors known to build up SOC, namely transient receptor potential canonical 1 (TRPC1) and Orai1, as well as their activator stromal interaction molecule 1 (STIM1). Calcium imaging reveals that SVZ cells display store-operated calcium entries. Pharmacological blockade of SOC with SKF-96365 or YM-58483 (also called BTP2) decreases proliferation, impairs self-renewal by shifting the type of SVZ stem cell division from symmetric proliferative to asymmetric, thereby reducing the stem cell population. Brain section immunostainings show that TRPC1, Orai1, and STIM1 are expressed in vivo, in SOX2-positive SVZ NSC. Injection of SKF-96365 in brain lateral ventricle diminishes SVZ cell proliferation and reduces the ability of SVZ cells to form neurospheres in vitro. The present study combining in vitro and in vivo approaches uncovers a major role for SOC in the control of SVZ NSC population and opens new fields of investigation for stem cell biology in health and disease. Stem Cells 2018. © AlphaMed Press 2018.

  20. Prostaglandin E2 Indicates Therapeutic Efficacy of Mesenchymal Stem Cells in Experimental Traumatic Brain Injury.

    Science.gov (United States)

    Kota, Daniel J; Prabhakara, Karthik S; Toledano-Furman, Naama; Bhattarai, Deepa; Chen, Qingzheng; DiCarlo, Bryan; Smith, Philippa; Triolo, Fabio; Wenzel, Pamela L; Cox, Charles S; Olson, Scott D

    2017-05-01

    Traumatic brain injury (TBI) is soon predicted to become the third leading cause of death and disability worldwide. After the primary injury, a complex set of secondary injuries develops hours and days later with prolonged neuroinflammation playing a key role. TBI and other inflammatory conditions are currently being treated in preclinical and clinical trials by a number of cellular therapies. Mesenchymal stem cells (MSC) are of great interest due to their widespread usage, safety, and relative ease to isolate and culture. However, there has been a wide range in efficacy reported using MSC clinically and in preclinical models, likely due to differences in cell preparations and a significant amount of donor variability. In this study, we seek to find a correlation between in vitro activity and in vivo efficacy. We designed assays to explore the responsiveness of MSC to immunological cues to address the immunomodulatory properties of MSC, one of their primary modes of therapeutic activity in TBI. Our results showed intrinsic differences in the immunomodulatory capacity of MSC preparations from different bone marrow and amniotic fluid donors. This difference mirrored the therapeutic capacity of the MSC in an experimental model of TBI, an effect confirmed using siRNA knockdown of COX2 followed by overexpressing COX2. Among the immunomodulatory factors assessed, the therapeutic benefit correlated with the secretion of prostaglandin E2 (PGE2 ) by MSC prior to treatment, suggesting that measurement of PGE2 could be a very useful potency marker to create an index of predicted efficacy for preparations of MSC to treat TBI. Stem Cells 2017;35:1416-1430. © 2017 AlphaMed Press.

  1. A cGMP-applicable expansion method for aggregates of human neural stem and progenitor cells derived from pluripotent stem cells or fetal brain tissue.

    Science.gov (United States)

    Shelley, Brandon C; Gowing, Geneviève; Svendsen, Clive N

    2014-06-15

    A cell expansion technique to amass large numbers of cells from a single specimen for research experiments and clinical trials would greatly benefit the stem cell community. Many current expansion methods are laborious and costly, and those involving complete dissociation may cause several stem and progenitor cell types to undergo differentiation or early senescence. To overcome these problems, we have developed an automated mechanical passaging method referred to as "chopping" that is simple and inexpensive. This technique avoids chemical or enzymatic dissociation into single cells and instead allows for the large-scale expansion of suspended, spheroid cultures that maintain constant cell/cell contact. The chopping method has primarily been used for fetal brain-derived neural progenitor cells or neurospheres, and has recently been published for use with neural stem cells derived from embryonic and induced pluripotent stem cells. The procedure involves seeding neurospheres onto a tissue culture Petri dish and subsequently passing a sharp, sterile blade through the cells effectively automating the tedious process of manually mechanically dissociating each sphere. Suspending cells in culture provides a favorable surface area-to-volume ratio; as over 500,000 cells can be grown within a single neurosphere of less than 0.5 mm in diameter. In one T175 flask, over 50 million cells can grow in suspension cultures compared to only 15 million in adherent cultures. Importantly, the chopping procedure has been used under current good manufacturing practice (cGMP), permitting mass quantity production of clinical-grade cell products.

  2. Corpus callosum atrophy in Wernicke's encephalopathy.

    Science.gov (United States)

    Lee, Soon-Tae; Jung, Young-Min; Na, Duk L; Park, Seong Ho; Kim, Manho

    2005-10-01

    Neuropathologic changes in Wernicke's encephalopathy (WE) involve variable brain structures. Corpus callosum involvement in WE, however, is largely unknown. The authors investigated the degree and the pattern of corpus callosum changes in WE according to the etiologies. Nineteen patients with WE (between 34 and 81 years) and 19 age- and sex-matched control participants were included. The total cross-sectional callosal area and 5 callosal subregions (C1-C5) were measured by tracing outer margins in the midsagittal sections. Subregions were determined by placing radial dividers with 10 rays. The pixel numbers for corpus callosums were calculated, and the values obtained were adjusted for head size variations. The causes of WE were alcoholism (10), intestinal surgery (5), anorexia (3), and hyperemesis gravidarum (1). The mean size of the total corpus callosum was significantly reduced in alcoholic WE (P< .001; 527.8 +/- 70.8 mm2 for alcoholic WE; 664.6 +/- 58.1 mm2 for the corresponding controls), but not in nonalcoholic WE. In subregion analysis, prefrontal callosum (C2) atrophy was the most prominent in alcoholic WE. In contrast, only splenium (C5) was atrophied in nonalcoholic WE. The degree of atrophy did not change throughout the follow-up period (mean 5.3 weeks). This study suggests that the extent and location of corpus callosum atrophy differs between alcoholic WE and nonalcoholic WE, implying separate contribution of alcohol neurotoxicity and nutritional deficiency.

  3. STEM?!?!

    Science.gov (United States)

    Merrill, Jen

    2012-01-01

    The author's son has been an engineer since birth. He never asked "why" as a toddler, it was always "how's it work?" So that he wanted a STEM-based home education was no big surprise. In this article, the author considers what kind of curricula would work best for her complex kid.

  4. Intra-Arterially Delivered Mesenchymal Stem Cells Are Not Detected in the Brain Parenchyma in an Alzheimer's Disease Mouse Model.

    Directory of Open Access Journals (Sweden)

    Na Kyung Lee

    Full Text Available Mesenchymal stem cells (MSCs have a promising role as a therapeutic agent for neurodegenerative diseases such as Alzheimer's disease (AD. Prior studies suggested that intra-arterially administered MSCs are engrafted into the brain in stroke or traumatic brain injury (TBI animal models. However, a controversial standpoint exists in terms of the integrity of the blood brain barrier (BBB in transgenic AD mice. The primary goal of this study was to explore the feasibility of delivering human umbilical cord-blood derived mesenchymal stem cells (hUCB-MSCs into the brains of non-transgenic WT (C3H/C57 and transgenic AD (APP/PS1 mice through the intra-arterial (IA route. Through two experiments, mice were infused with hUCB-MSCs via the right internal carotid artery and were sacrificed at two different time points: 6 hours (experiment 1 or 5 minutes (experiment 2 after infusion. In both experiments, no cells were detected in the brain parenchyma while MSCs were detected in the cerebrovasculature in experiment 2. The results from this study highlight that intra-arterial delivery of MSCs is not the most favorable route to be implemented as a potential therapeutic approach for AD.

  5. Presenilins are required for maintenance of neural stem cells in the developing brain

    Directory of Open Access Journals (Sweden)

    Kim Woo-Young

    2008-01-01

    Full Text Available Abstract The early embryonic lethality of mutant mice bearing germ-line deletions of both presenilin genes precluded the study of their functions in neural development. We therefore employed the Cre-loxP technology to generate presenilin conditional double knockout (PS cDKO mice, in which expression of both presenilins is inactivated in neural progenitor cells (NPC or neural stem cells and their derivative neurons and glia beginning at embryonic day 11 (E11. In PS cDKO mice, dividing NPCs labeled by BrdU are decreased in number beginning at E13.5. By E15.5, fewer than 20% of NPCs remain in PS cDKO mice. The depletion of NPCs is accompanied by severe morphological defects and hemorrhages in the PS cDKO embryonic brain. Interkinetic nuclear migration of NPCs is also disrupted in PS cDKO embryos, as evidenced by displacement of S-phase and M-phase nuclei in the ventricular zone of the telencephalon. Furthermore, the depletion of neural progenitor cells in PS cDKO embryos is due to NPCs exiting cell cycle and differentiating into neurons rather than reentering cell cycle between E13.5 and E14.5 following PS inactivation in most NPCs. The length of cell cycle, however, is unchanged in PS cDKO embryos. Expression of Notch target genes, Hes1 and Hes5, is significantly decreased in PS cDKO brains, whereas Dll1 expression is up-regulated, indicating that Notch signaling is effectively blocked by PS inactivation. These findings demonstrate that presenilins are essential for neural progenitor cells to re-enter cell cycle and thus ensure proper expansion of neural progenitor pool during embryonic neural development.

  6. Robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery from stroke: updates and advances.

    Science.gov (United States)

    Boninger, Michael L; Wechsler, Lawrence R; Stein, Joel

    2014-11-01

    The aim of this study was to describe the current state and latest advances in robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery for stroke. The authors of this summary recently reviewed this work as part of a national presentation. The article represents the information included in each area. Each area has seen great advances and challenges as products move to market and experiments are ongoing. Robotics, stem cells, and brain-computer interfaces all have tremendous potential to reduce disability and lead to better outcomes for patients with stroke. Continued research and investment will be needed as the field moves forward. With this investment, the potential for recovery of function is likely substantial.

  7. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  8. Curved reformat of the paediatric brain MRI into a 'flat-earth map' - standardised method for demonstrating cortical surface atrophy resulting from hypoxic-ischaemic encephalopathy.

    Science.gov (United States)

    Simpson, Ewan; Andronikou, Savvas; Vedajallam, Schadie; Chacko, Anith; Thai, Ngoc Jade

    2016-09-01

    Hypoxic-ischaemic encephalopathy is optimally imaged with brain MRI in the neonatal period. However neuroimaging is often also performed later in childhood (e.g., when parents seek compensation in cases of alleged birth asphyxia). We describe a standardised technique for creating two curved reconstructions of the cortical surface to show the characteristic surface changes of hypoxic-ischaemic encephalopathy in children imaged after the neonatal period. The technique was applied for 10 cases of hypoxic-ischaemic encephalopathy and also for age-matched healthy children to assess the visibility of characteristic features of hypoxic-ischaemic encephalopathy. In the abnormal brains, fissural or sulcal widening was seen in all cases and ulegyria was identifiable in 7/10. These images could be used as a visual aid for communicating MRI findings to clinicians and other interested parties.

  9. Brain plasticity, cognitive functions and neural stem cells: a pivotal role for the brain-specific neural master gene |-SRGAP2-FAM72-|.

    Science.gov (United States)

    Ho, Nguyen Thi Thanh; Kutzner, Arne; Heese, Klaus

    2017-12-20

    Due to an aging society with an increased dementia-induced threat to higher cognitive functions, it has become imperative to understand the molecular and cellular events controlling the memory and learning processes in the brain. Here, we suggest that the novel master gene pair |-SRGAP2-FAM72-| (SLIT-ROBO Rho GTPase activating the protein 2, family with sequence similarity to 72) reveals a new dogma for the regulation of neural stem cell (NSC) gene expression and is a distinctive player in the control of human brain plasticity. Insight into the specific regulation of the brain-specific neural master gene |-SRGAP2-FAM72-| may essentially contribute to novel therapeutic approaches to restore or improve higher cognitive functions.

  10. Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

    Science.gov (United States)

    Tajiri, Naoki; Kaneko, Yuji; Shinozuka, Kazutaka; Ishikawa, Hiroto; Yankee, Ernest; McGrogan, Michael; Case, Casey; Borlongan, Cesar V

    2013-01-01

    Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

  11. Brain stem activity changes associated with restored sympathetic drive following CPAP treatment in OSA subjects: a longitudinal investigation.

    Science.gov (United States)

    Lundblad, Linda C; Fatouleh, Rania H; McKenzie, David K; Macefield, Vaughan G; Henderson, Luke A

    2015-08-01

    Obstructive sleep apnea (OSA) is associated with significantly elevated muscle sympathetic nerve activity (MSNA), leading to hypertension and increased cardiovascular morbidity. Although little is known about the mechanisms responsible for the sympathoexcitation, we have recently shown that the elevated MSNA in OSA is associated with altered neural processing in various brain stem sites, including the dorsolateral pons, rostral ventrolateral medulla, medullary raphe, and midbrain. Given the risk associated with elevated MSNA, we aimed to determine if treatment of OSA with continuous positive airway pressure (CPAP) would reduce the elevated MSNA and reverse the brain stem functional changes associated with the elevated MSNA. We performed concurrent recordings of MSNA and blood oxygen level-dependent (BOLD) signal intensity of the brain stem, using high-resolution functional magnetic resonance imaging, in 15 controls and 13 subjects with OSA, before and after 6 mo CPAP treatment. As expected, 6 mo of CPAP treatment significantly reduced MSNA in subjects with OSA, from 54 ± 4 to 23 ± 3 bursts/min and from 77 ± 7 to 36 ± 3 bursts/100 heart beats. Importantly, we found that MSNA-coupled changes in BOLD signal intensity within the dorsolateral pons, medullary raphe, and rostral ventrolateral medulla returned to control levels. That is, CPAP treatment completely reversed brain stem functional changes associated with elevated MSNA in untreated OSA subjects. These data highlight the effectiveness of CPAP treatment in reducing one of the most significant health issues associated with OSA, that is, elevated MSNA and its associated elevated morbidity. Copyright © 2015 the American Physiological Society.

  12. Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brain stem preparation of rat.

    Science.gov (United States)

    Jones, Sarah E; Dutschmann, Mathias

    2016-05-01

    Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex (n = 5), at obex (n = 5), and 1.5 (n = 7) and 3 mm (n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Bötzinger complex (pre-BötC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high-amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high-amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation. Copyright © 2016 the American Physiological Society.

  13. Neuroanesthesia management of neurosurgery of brain stem tumor requiring neurophysiology monitoring in an iMRI OT setting

    Directory of Open Access Journals (Sweden)

    Sabbagh Abdulrahman

    2009-01-01

    Full Text Available This report describes a rare case of ventrally exophytic pontine glioma describing operative and neuroanesthesia management. The combination of intraoperative neuromonitoring was used. It constituted: Brain stem evoked responses/potentials, Motor EP: recording from cranial nerve supplied muscle, and Sensory EP: Medial/tibial. Excision of the tumor was done with intra-operative magnatic resonance imaging (iMRI, which is considered a new modality.

  14. CRISPR/Cas9-induced disruption of gene expression in mouse embryonic brain and single neural stem cells in vivo.

    Science.gov (United States)

    Kalebic, Nereo; Taverna, Elena; Tavano, Stefania; Wong, Fong Kuan; Suchold, Dana; Winkler, Sylke; Huttner, Wieland B; Sarov, Mihail

    2016-03-01

    We have applied the CRISPR/Cas9 system in vivo to disrupt gene expression in neural stem cells in the developing mammalian brain. Two days after in utero electroporation of a single plasmid encoding Cas9 and an appropriate guide RNA (gRNA) into the embryonic neocortex of Tis21::GFP knock-in mice, expression of GFP, which occurs specifically in neural stem cells committed to neurogenesis, was found to be nearly completely (≈ 90%) abolished in the progeny of the targeted cells. Importantly, upon in utero electroporation directly of recombinant Cas9/gRNA complex, near-maximal efficiency of disruption of GFP expression was achieved already after 24 h. Furthermore, by using microinjection of the Cas9 protein/gRNA complex into neural stem cells in organotypic slice culture, we obtained disruption of GFP expression within a single cell cycle. Finally, we used either Cas9 plasmid in utero electroporation or Cas9 protein complex microinjection to disrupt the expression of Eomes/Tbr2, a gene fundamental for neocortical neurogenesis. This resulted in a reduction in basal progenitors and an increase in neuronal differentiation. Thus, the present in vivo application of the CRISPR/Cas9 system in neural stem cells provides a rapid, efficient and enduring disruption of expression of specific genes to dissect their role in mammalian brain development. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  15. Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier.

    Science.gov (United States)

    Biancardi, Vinicia Campana; Son, Sook Jin; Ahmadi, Sahra; Filosa, Jessica A; Stern, Javier E

    2014-03-01

    Angiotensin II-mediated vascular brain inflammation emerged as a novel pathophysiological mechanism in neurogenic hypertension. However, the precise underlying mechanisms and functional consequences in relation to blood-brain barrier (BBB) integrity and central angiotensin II actions mediating neurohumoral activation in hypertension are poorly understood. Here, we aimed to determine whether BBB permeability within critical hypothalamic and brain stem regions involved in neurohumoral regulation was altered during hypertension. Using digital imaging quantification after intravascularly injected fluorescent dyes and immunohistochemistry, we found increased BBB permeability, along with altered key BBB protein constituents, in spontaneously hypertensive rats within the hypothalamic paraventricular nucleus, the nucleus of the solitary tract, and the rostral ventrolateral medulla, all critical brain regions known to contribute to neurohumoral activation during hypertension. BBB disruption, including increased permeability and downregulation of constituent proteins, was prevented in spontaneously hypertensive rats treated with the AT1 receptor antagonist losartan, but not with hydralazine, a direct vasodilator. Importantly, we found circulating angiotensin II to extravasate into these brain regions, colocalizing with neurons and microglial cells. Taken together, our studies reveal a novel angiotensin II-mediated feed-forward mechanism during hypertension, by which circulating angiotensin II evokes increased BBB permeability, facilitating in turn its access to critical brain regions known to participate in blood pressure regulation.

  16. Susceptibility-weighted imaging of the venous networks around the brain stem

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Ming; Lin, Zhong-Xiao; Zhang, Nu [Wenzhou Medical University, Department of Neurosurgery, The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou (China); Zhang, Xiao-Fen; Qiao, Hui-Huang; Chen, Cheng-Chun [Wenzhou Medical University, Department of Human Anatomy, Wenzhou (China); Ren, Chuan-Gen; Li, Jian-Ce [Wenzhou Medical University, Department of Radiology, The 1nd Affiliated Hospital of Wenzhou Medical University, Wenzhou (China)

    2014-10-18

    The venous network of the brainstem is complex and significant. Susceptibility-weighted imaging (SWI) is a practical technique which is sensitive to veins, especially tiny veins. Our purpose of this study was to evaluate the visualization of the venous network of brainstem by using SWI at 3.0 T. The occurrence rate of each superficial veins of brainstem was evaluated by using SWI on a 3 T MR imaging system in 60 volunteers. The diameter of the lateral mesencephalic vein and peduncular vein were measured by SWI using the reconstructed mIP images in the sagittal view. And the outflow of the veins of brainstem were studied and described according to the reconstructed images. The median anterior pontomesencephalic vein, median anterior medullary vein, peduncular vein, right vein of the pontomesencephalic sulcus, and right lateral anterior pontomesencephalic vein were detected in all the subjects (100 %). The outer diameter of peduncular vein was 1.38 ± 0.26 mm (range 0.8-1.8 mm). The lateral mesencephalic vein was found in 75 % of the subjects and the mean outer diameter was 0.81 ± 0.2 mm (range 0.5-1.2 mm). The inner veins of mesencephalon were found by using SWI. The venous networks around the brain stem can be visualized by SWI clearly. This result can not only provide data for anatomical study, but also may be available for the surgical planning in the infratentorial region. (orig.)

  17. Subacute sclerosing panencephalitis presenting as acute cerebellar ataxia and brain stem hyperintensities.

    Science.gov (United States)

    Saini, Arushi Gahlot; Sankhyan, Naveen; Padmanabh, Hansashree; Sahu, Jitendra Kumar; Vyas, Sameer; Singhi, Pratibha

    2016-05-01

    Subacute sclerosing panencephalitis is a devastating neurodegenerative disease with a characteristic clinical course. Atypical presentations may be seen in 10% of the cases. To describe the atypical clinical and radiological features of SSPE in a child form endemic country. A 5-year-old boy presented with acute-onset cerebellar ataxia without associated encephalopathy, focal motor deficits, seizures or cognitive decline. He had varicella-like illness with vesicular, itchy truncal rash erupting one month prior to the onset of these symptoms. He underwent detailed neurological assessment, relevant laboratory and radiological investigations. Neuroimaging revealed peculiar brain stem lesions involving the pons and cerebellum suggestive of demyelination. With a presumptive diagnosis of clinically isolated syndrome of demyelination, he was administered pulse methylprednisolone (30 mg/kg/day for 5 days). Four weeks later he developed myoclonic jerks. Electroencephalogram showed characteristic periodic complexes time-locked with myoclonus. CSF and serum anti-measles antibody titres were elevated (1:625). Our report highlights that subacute sclerosing panencephalitis can present atypically as isolated acute cerebellar ataxia and peculiar involvement of longitudinal and sparing of transverse pontine fibres. The predominant brainstem abnormalities in the clinical setting may mimick acute demyelinating syndrome. Hence, it is important to recognize these features of subacute sclerosing panencephalitis in children, especially in the endemic countries. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  18. [Muscle fiber atrophy].

    Science.gov (United States)

    Nonaka, Ikuya

    2012-01-01

    Muscle fibers have been classified into two major forms of red (slow twitch) and white (fast twitch) muscles. The red muscle utilizes lipid as energy source through mitochondrial metabolism and function to sustain the position against gravity (sometimes called as antigravity muscle). Under microgravity the red muscle is selectively involved. In our unloading study by hindlimb suspension experiment on rats, the one of the representative red muscle of soleus muscle underwent rapid atrophy; they reduced their weights about 50% after 2 week-unloading. In addition, myofibrils were occasionally markedly disorganized with selective thin filament loss. Mitochondria in the degenerated area were decreased in number. The white muscle fibers in the soleus muscle had mostly transformed to the red ones. It took about 1 month to recover morphologically. The satellite cell playing a major role in muscle regeneration was not activated. There still remained unsolved what are the mechanosensors to keep muscle function under normal gravity. Dr Nikawa's group proposed that one of ubiquitin ligases, Cbl-b is activated under microgravity and induces muscle fiber degeneration. There might be many factors to induce muscle atrophy and degeneration under microgravity. Further study is necessary to explore the pathomechanism of muscle atrophy in disused and under immobility conditions.

  19. Non-virally engineered human adipose mesenchymal stem cells produce BMP4, target brain tumors, and extend survival.

    Science.gov (United States)

    Mangraviti, Antonella; Tzeng, Stephany Y; Gullotti, David; Kozielski, Kristen L; Kim, Jennifer E; Seng, Michael; Abbadi, Sara; Schiapparelli, Paula; Sarabia-Estrada, Rachel; Vescovi, Angelo; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Green, Jordan J; Quinones-Hinojosa, Alfredo

    2016-09-01

    There is a need for enabling non-viral nanobiotechnology to allow safe and effective gene therapy and cell therapy, which can be utilized to treat devastating diseases such as brain cancer. Human adipose-derived mesenchymal stem cells (hAMSCs) display high anti-glioma tropism and represent a promising delivery vehicle for targeted brain tumor therapy. In this study, we demonstrate that non-viral, biodegradable polymeric nanoparticles (NPs) can be used to engineer hAMSCs with higher efficacy (75% of cells) than leading commercially available reagents and high cell viability. To accomplish this, we engineered a poly(beta-amino ester) (PBAE) polymer structure to transfect hAMSCs with significantly higher efficacy than Lipofectamine™ 2000. We then assessed the ability of NP-engineered hAMSCs to deliver bone morphogenetic protein 4 (BMP4), which has been shown to have a novel therapeutic effect by targeting human brain tumor initiating cells (BTIC), a source of cancer recurrence, in a human primary malignant glioma model. We demonstrated that hAMSCs genetically engineered with polymeric nanoparticles containing BMP4 plasmid DNA (BMP4/NP-hAMSCs) secrete BMP4 growth factor while maintaining their multipotency and preserving their migration and invasion capacities. We also showed that this approach can overcome a central challenge for brain therapeutics, overcoming the blood brain barrier, by demonstrating that NP-engineered hAMSCs can migrate to the brain and penetrate the brain tumor after both intranasal and systemic intravenous administration. Critically, athymic rats bearing human primary BTIC-derived tumors and treated intranasally with BMP4/NP-hAMSCs showed significantly improved survival compared to those treated with control GFP/NP-hAMCSs. This study demonstrates that synthetic polymeric nanoparticles are a safe and effective approach for stem cell-based cancer-targeting therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  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. [Posterior cortical atrophy with progressive visual agnosia].

    Science.gov (United States)

    Zarranz, J J; Lasa, A; Fernández, M; Lezcano, E; Pérez Bas, M; Varona, L; Ruiz, J; Beristain, X

    1995-03-01

    Interest in progressive focal cerebral syndromes associated with classical degenerative diseases has increased in recent years. Descriptions of posterior cortical atrophy with progressive visual agnosia are relatively rare. We present 5 patients (2 women) ranging in age between 57 and 72 years old. In all cases symptoms began and progressed with no known etiology. All cases were sporadic. The main clinical signs are difficulty in recognizing objects, colors, persons or places; topographical disorientation and visual memory alterations; alexia, simultagnosia, loss of ocular fixing and optic ataxia. Some patients presented other disturbances of praxis or memory and 2 progressed to global dementia. Language function was preserved and behavioral disturbances did not develop. The amplitude of the P100 visual evoked potential was low but latency was normal in 4 patients and prolonged in 1. Brain images showed atrophy and hypoperfusion in the parieto-occipital area. The neuropathology status of these patients is unknown.

  2. PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes.

    Science.gov (United States)

    Choi, Insup; Choi, Dong-Joo; Yang, Haijie; Woo, Joo Hong; Chang, Mi-Yoon; Kim, Joo Yeon; Sun, Woong; Park, Sang-Myun; Jou, Ilo; Lee, Sang-Hun; Lee, Sang Hoon; Joe, Eun-Hye

    2016-01-08

    Mutation of PTEN-induced putative kinase 1 (PINK1) causes autosomal recessive early-onset Parkinson's disease (PD). Despite of its ubiquitous expression in brain, its roles in non-neuronal cells such as neural stem cells (NSCs) and astrocytes were poorly unknown. We show that PINK1 expression increases from embryonic day 12 to postnatal day 1 in mice, which represents the main period of brain development. PINK1 expression also increases during neural stem cell (NSC) differentiation. Interestingly, expression of GFAP (a marker of astrocytes) was lower in PINK1 knockout (KO) mouse brain lysates compared to wild-type (WT) lysates at postnatal days 1-8, whereas there was little difference in the expression of markers for other brain cell types (e.g., neurons and oligodendrocytes). Further experiments showed that PINK1-KO NSCs were defective in their differentiation to astrocytes, producing fewer GFAP-positive cells compared to WT NSCs. However, the KO and WT NSCs did not differ in their self-renewal capabilities or ability to differentiate to neurons and oligodendrocytes. Interestingly, during differentiation of KO NSCs there were no defects in mitochondrial function, and there were not changes in signaling molecules such as SMAD1/5/8, STAT3, and HES1 involved in differentiation of NSCs into astrocytes. In brain sections, GFAP-positive astrocytes were more sparsely distributed in the corpus callosum and substantia nigra of KO animals compared with WT. Our study suggests that PINK1 deficiency causes defects in GFAP-positive astrogliogenesis during brain development and NSC differentiation, which may be a factor to increase risk for PD.

  3. The role of CXC chemokine ligand (CXCL)12-CXC chemokine receptor (CXCR)4 signalling in the migration of neural stem cells towards a brain tumour

    NARCIS (Netherlands)

    van der Meulen, A. A. E.; Biber, K.; Lukovac, S.; Balasubramaniyan, V.; den Dunnen, W. F. A.; Boddeke, H. W. G. M.; Mooij, J. J. A.

    2009-01-01

    Aims: It has been shown that neural stem cells (NSCs) migrate towards areas of brain injury or brain tumours and that NSCs have the capacity to track infiltrating tumour cells. The possible mechanism behind the migratory behaviour of NSCs is not yet completely understood. As chemokines are involved

  4. Multipotent neural stem cells generate glial cells of the central complex through transit amplifying intermediate progenitors in Drosophila brain development.

    Science.gov (United States)

    Viktorin, Gudrun; Riebli, Nadia; Popkova, Anna; Giangrande, Angela; Reichert, Heinrich

    2011-08-15

    The neural stem cells that give rise to the neural lineages of the brain can generate their progeny directly or through transit amplifying intermediate neural progenitor cells (INPs). The INP-producing neural stem cells in Drosophila are called type II neuroblasts, and their neural progeny innervate the central complex, a prominent integrative brain center. Here we use genetic lineage tracing and clonal analysis to show that the INPs of these type II neuroblast lineages give rise to glial cells as well as neurons during postembryonic brain development. Our data indicate that two main types of INP lineages are generated, namely mixed neuronal/glial lineages and neuronal lineages. Genetic loss-of-function and gain-of-function experiments show that the gcm gene is necessary and sufficient for gliogenesis in these lineages. The INP-derived glial cells, like the INP-derived neuronal cells, make major contributions to the central complex. In postembryonic development, these INP-derived glial cells surround the entire developing central complex neuropile, and once the major compartments of the central complex are formed, they also delimit each of these compartments. During this process, the number of these glial cells in the central complex is increased markedly through local proliferation based on glial cell mitosis. Taken together, these findings uncover a novel and complex form of neurogliogenesis in Drosophila involving transit amplifying intermediate progenitors. Moreover, they indicate that type II neuroblasts are remarkably multipotent neural stem cells that can generate both the neuronal and the glial progeny that make major contributions to one and the same complex brain structure. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation.

    Science.gov (United States)

    St John, James A; Walkden, Heidi; Nazareth, Lynn; Beagley, Kenneth W; Ulett, Glen C; Batzloff, Michael R; Beacham, Ifor R; Ekberg, Jenny A K

    2016-09-01

    Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 μm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. Study of brain-derived neurotrophic factor gene transgenic neural stem cells in the rat retina.

    Science.gov (United States)

    Zhou, Xue-mei; Yuan, Hui-ping; Wu, Dong-lai; Zhou, Xin-rong; Sun, Da-wei; Li, Hong-yi; Shao, Zheng-bo

    2009-07-20

    Neural stem cells (NSCs) transplantation and gene therapy have been widely investigated for treating the cerebullar and myelonic injuries, however, studies on the ophthalmology are rare. The aim of this study was to investigate the migration and differentiation of brain-derived neurotrophic factor (BDNF) gene transgenic NSCs transplanted into the normal rat retinas. NSCs were cultured and purified in vitro and infected with recombinant retrovirus pLXSN-BDNF and pLXSN respectively, to obtain the BDNF overexpressed NSCs (BDNF-NSCs) and control cells (p-NSCs). The expression of BDNF genes in two transgenic NSCs and untreated NSCs were measured by fluorescent quantitative polymerase chain reaction (FQ-PCR) and enzyme-linked immunosorbent assay (ELISA). BDNF-NSCs and NSCs were infected with adeno-associated viruses-enhanced green fluorescent protein (AAV-EGFP) to track them in vivo and served as donor cells for transplantation into the subretinal space of normal rat retinas, phosphated buffer solution (PBS) served as pseudo transplantation for a negative control. Survival, migration, and differentiation of donor cells in host retinas were observed and analyzed with Heidelberg retina angiograph (HRA) and immunohistochemistry, respectively. NSCs were purified successfully by limiting dilution assay. The expression of BDNF gene in BDNF-NSCs was the highest among three groups both at mRNA level tested by FQ-PCR (P neuron more efficiently compared with the control NSCs 2 months after transplantation. The seed cells of NSCs highly secreting BDNF were established. BDNF can promote NSCs to migrate and differentiate into neural cells in the normal host retinas.

  7. Gamma knife radiosurgery of the symptomatic brain stem cavernous angioma with low marginal dose.

    Science.gov (United States)

    Kim, Byung Sup; Yeon, Je Young; Kim, Jong-Soo; Hong, Seung-Chyul; Lee, Jung-Il

    2014-11-01

    To analyze the outcome of gamma knife radiosurgery (GKS) using low marginal dose for the symptomatic brain stem cavernous angioma (BSCA). 39 patients (16 males, 23 females) were treated with GKS for BSCA from January 1997 to September 2012. Clinical data were analyzed retrospectively. The mean age was 41.5 years. All patients had a history of symptomatic bleeding once or more before performing GKS. Mean volume of BSCA was 1095.3mm(3) and median prescribed marginal dose was 13 Gy. Mean follow-up period since diagnosis was 4.1 years. The number of hemorrhagic events between initial diagnosis and GKS was 5 over a total of 14.9 patients-years with annual hemorrhagic rate of 33.6%. Following GKS, there were five hemorrhagic events within the first 2 years (8.1%/year) and two after the first 2 years (2.4%/year). The difference was not statistically significant. Neurologic status improved in 24 patients (61.5%), and stationary in eleven (28.2%). 4 patients (10.3%) experienced the exacerbation of symptoms at the last follow-up and none of them were related to the radiation injury. Significant volume reduction after GKS was observed in 24 patients (61.5%). Surgical excision was performed in one patient due to swelling and rebleeding after GKS. Age at presentation, sex, mass size of BSCA, and location, GKS dose did not affect post-GKS hemorrhage. GKS for BSCA using relatively low marginal dose is safe and effective. Long-term prospective study is needed to confirm the optimal dose for BSCA. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Mitochondria modify exercise-induced development of stem cell-derived neurons in the adult brain

    National Research Council Canada - National Science Library

    Steib, Kathrin; Schäffner, Iris; Jagasia, Ravi; Ebert, Birgit; Lie, D Chichung

    2014-01-01

    Neural stem cells in the adult mammalian hippocampus continuously generate new functional neurons, which modify the hippocampal network and significantly contribute to cognitive processes and mood regulation...

  9. Induction of Perivascular Neural Stem Cells and Possible Contribution to Neurogenesis Following Transient Brain Ischemia/Reperfusion Injury.

    Science.gov (United States)

    Nakata, Masayo; Nakagomi, Takayuki; Maeda, Mitsuyo; Nakano-Doi, Akiko; Momota, Yoshihiro; Matsuyama, Tomohiro

    2017-04-01

    Recent therapeutic advances have increased the likelihood of recanalizing the obstructed brain arteries in patients with stroke. Therefore, it is important to understand the fate of neural cells under transient ischemia/reperfusion injury. Accumulating evidence shows that neurogenesis occurs in perivascular regions following brain injury, although the precise mechanism and origin of these newborn neurons under transient ischemia/reperfusion injury remain unclear. Using a mouse model of transient brain ischemia/reperfusion injury, we found that neural stem cells (NSCs) develop within injured areas. This induction of NSCs following ischemia/reperfusion injury was observed even in response to nonlethal ischemia, although massive numbers of NSCs were induced by lethal ischemia. Immunohistochemical and immunoelectron microscopic studies indicated that platelet-derived growth factor receptor beta-positive (PDGFRβ+) pericytes within injured areas following nonlethal ischemia began to express the NSC marker nestin as early as 3 days after transient ischemia/reperfusion. Some PDGFRβ+ pericytes expressed the immature neuronal marker doublecortin at day 7. These findings indicate that brain pericytes are a potential source of the perivascular NSCs that generate neuronal cells under lethal and nonlethal ischemic conditions following transient ischemia/reperfusion. Thus, brain pericytes might be a target for neurogenesis mediation in patients with nonlethal and lethal ischemia following transient ischemia/reperfusion injury.

  10. CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway.

    Directory of Open Access Journals (Sweden)

    Mayumi Jijiwa

    Full Text Available Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6 in BTSC of a subset of glioblastoma multiforme (GBM. Patients with CD44(high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44(high GBM but not from CD44(low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN, increased expression of phosphorylated AKT in CD44(high GBM, but not in CD44(low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKT pathway.

  11. Efferents from the optic tectum to the brain stem in the Japanese quail (Coturnix japonica). Anterogradely biocytin method.

    Science.gov (United States)

    Sugita, S; Fujikake, N; Sugahara, K; Fujiwara, K; Wada, N

    1996-05-01

    Efferents from the optic tectum to the brain stem in the Japanese quail (Coturnix japonica) were studied with the anterogradely biocytin method. After injection of biocytin into the ipsilateral optic tectum, labeled terminals were seen in the rotund nucleus (Rt), neuropil part of the ventral lateral geniculate nucleus (GLnv), principal part of the dorsal lateral geniculate nucleus, lateral part of the dorsolateral thalamic nucleus, triangular nucleus (T), superficial parvocellular nucleus (SPC), pretectal nucleus, pretectal area (PA), subpretectal nucleus, central gray matter (GC), isthimo optic nucleus (ION), magnocellular and parvocellular parts of the isthimo nuclei (Imc and Ipc), semilunar nucleus (SLu), lateral and medial pontine nuclei and reticular formation (FRM) of the medulla, ipsilaterally. Labeled fibers were seen in the septomesencephalic tract nucleus, FRM, interstitio-paraetecto-subpraetectal nucleus, and the dorsal and ventral tectoreticular tracts (TRd and TRv). In the contralateral brain stem, labeled terminals were seen in the Rt, T. FRM, PA and paramedian nucleus. The contralateral terminals were remarkably fewer than those of the ipsilateral side. The present findings of the labeled terminals of the SPC and the GC at the level of the mesencephalic nucleus of the trigeminal nerve (MnT), and the topographic projection from optic tectum to the Rt in the thalamus, were original observations in the avian. The labeled terminals in the GLnv, Ipc, Imc and ION showed topographical projections from the optic tectum. Pathways to the contralateral brain stem were via the commissure posterior, ventral supraoptic decussation, and the predorsal bundle. The present results suggest that tectofugal impulses in the quail relate to various functions with special relation to the function of the GC at the level of the MnT as well as a visual function.

  12. Effects of the pyrethroid insecticide, deltamethrin, on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice

    DEFF Research Database (Denmark)

    Rekling, J C; Theophilidis, G

    1995-01-01

    We have studied the action of deltamethrin on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice. Deltamethrin depolarized the hypoglossal motoneurons, increased the background synaptic noise and reduced the frequency and amplitude of current elicited action...... potentials. Deltamethrin transiently increased the frequency of the respiratory rhythm. Inspiratory potentials in hypoglossal motoneurons were decreased in amplitude and increased in duration. In conclusion, deltamethrin perturbs the respiratory output from the hypoglossal nucleus through postsynaptic...... actions on hypoglossal motoneurons and by affecting the inspiratory synaptic drive....

  13. Atrophy of the parietal lobe in preclinical dementia

    NARCIS (Netherlands)

    Jacobs, H.I.L.; van Boxtel, M.P.J.; Uylings, H.B.M.; Gronenschild, E.H.B.M.; Verhey, F.R.; Jolles, J.

    2011-01-01

    Cortical grey matter atrophy patterns have been reported in healthy ageing and Alzheimer disease (AD), but less consistently in the parietal regions of the brain. We investigated cortical grey matter volume patterns in parietal areas. The grey matter of the somatosensory cortex, superior and

  14. Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

    Directory of Open Access Journals (Sweden)

    Dong-Kyu Jang

    2011-01-01

    Full Text Available This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (<.05. MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway.

  15. Hind brain agenesis a rare imaging findings in cerebro cerebellar lissencephalic syndrome.

    Science.gov (United States)

    Mundaganur, Praveen M; Solwalkar, Pradeep; Nimbal, Vishal

    2014-01-01

    A case report of cerebro cerebellar lissencephaly shows complete agenesis of cerebellum and brainstem which is rare imaging finding of group lissencephaly (type I lissencephaly). Though agenesis of cerebellum and brainstem were included in literature, in most of the cases we saw a hypoplasia or atrophy of cerebellum in lissencephaly syndrome. The CT scan findings of this patient shows features of lissencephaly with complete agenesis of brain stem and cerebellum associated with multiple congenital abnormalities.

  16. Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells.

    Science.gov (United States)

    Suzuki, Ikuo K; Vanderhaeghen, Pierre

    2015-09-15

    The human brain is arguably the most complex structure among living organisms. However, the specific mechanisms leading to this complexity remain incompletely understood, primarily because of the poor experimental accessibility of the human embryonic brain. Over recent years, technologies based on pluripotent stem cells (PSCs) have been developed to generate neural cells of various types. While the translational potential of PSC technologies for disease modeling and/or cell replacement therapies is usually put forward as a rationale for their utility, they are also opening novel windows for direct observation and experimentation of the basic mechanisms of human brain development. PSC-based studies have revealed that a number of cardinal features of neural ontogenesis are remarkably conserved in human models, which can be studied in a reductionist fashion. They have also revealed species-specific features, which constitute attractive lines of investigation to elucidate the mechanisms underlying the development of the human brain, and its link with evolution. © 2015. Published by The Company of Biologists Ltd.

  17. Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients

    OpenAIRE

    Schottlaender, Lucia V.; Conceição Bettencourt; Kiely, Aoife P; Annapurna Chalasani; Viruna Neergheen; Holton, Janice L.; Iain Hargreaves; Henry Houlden

    2016-01-01

    Background The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10) in brain tissue of multiple system atrophy (MSA) patients differ from those in elderly controls and in patients with other neurodegenerative diseases. Methods Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA) type, 6 striatonigral degeneration (SND) type, and 5 mixed type] was used for this study. Elderly controls (n = 37) as ...

  18. Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain.

    Directory of Open Access Journals (Sweden)

    Daria Namestnikova

    Full Text Available In vivo tracking of transplanted mesenchymal stem cells (MSCs migration and homing is vital for understanding the mechanisms of beneficial effects of MSCs transplantation in animal models of diseases and in clinical trials. Transplanted cells can be labeled with superparamagnetic iron oxide (SPIO particles and visualized in vivo using a number of iron sensitive MRI techniques. However, the applicability of those techniques for SPIO-labeled MSCs tracking in live brain has not been sufficiently investigated. The goal of this study was to estimate the efficiency of various MRI techniques of SPIO-labeled cell tracing in the brain. To achieve that goal, the precision and specificity of T2WI, T2*WI and SWI (Susceptibility-Weighted Imaging techniques of SPIO-labeled MSCs tracing in vitro and in live rat brain were for the first time compared in the same experiment. We have shown that SWI presents the most sensitive pulse sequence for SPIO-labeled MSCs MR visualization. After intracerebral administration due to limitations caused by local micro-hemorrhages the visualization threshold was 102 cells, while after intra-arterial transplantation SWI permitted detection of several cells or even single cells. There is just one publication claiming detection of individual SPIO-labeled MSCs in live brain, while the other state much lower sensitivity, describe detection of different cell types or high resolution tracing of MSCs in other tissues. This study confirms the possibility of single cell tracing in live brain and outlines the necessary conditions. SWI is a method convenient for the detection of single SPIO labeled MSCs and small groups of SPIO labeled MSCs in brain tissue and can be appropriate for monitoring migration and homing of transplanted cells in basic and translational neuroscience.

  19. Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain.

    Science.gov (United States)

    Namestnikova, Daria; Gubskiy, Ilya; Kholodenko, Irina; Melnikov, Pavel; Sukhinich, Kirill; Gabashvili, Anna; Vishnevskiy, Daniil; Soloveva, Anastasia; Abakumov, Maxim; Vakhrushev, Igor; Lupatov, Alexei; Chekhonin, Vladimir; Gubsky, Leonid; Yarygin, Konstantin

    2017-01-01

    In vivo tracking of transplanted mesenchymal stem cells (MSCs) migration and homing is vital for understanding the mechanisms of beneficial effects of MSCs transplantation in animal models of diseases and in clinical trials. Transplanted cells can be labeled with superparamagnetic iron oxide (SPIO) particles and visualized in vivo using a number of iron sensitive MRI techniques. However, the applicability of those techniques for SPIO-labeled MSCs tracking in live brain has not been sufficiently investigated. The goal of this study was to estimate the efficiency of various MRI techniques of SPIO-labeled cell tracing in the brain. To achieve that goal, the precision and specificity of T2WI, T2*WI and SWI (Susceptibility-Weighted Imaging) techniques of SPIO-labeled MSCs tracing in vitro and in live rat brain were for the first time compared in the same experiment. We have shown that SWI presents the most sensitive pulse sequence for SPIO-labeled MSCs MR visualization. After intracerebral administration due to limitations caused by local micro-hemorrhages the visualization threshold was 102 cells, while after intra-arterial transplantation SWI permitted detection of several cells or even single cells. There is just one publication claiming detection of individual SPIO-labeled MSCs in live brain, while the other state much lower sensitivity, describe detection of different cell types or high resolution tracing of MSCs in other tissues. This study confirms the possibility of single cell tracing in live brain and outlines the necessary conditions. SWI is a method convenient for the detection of single SPIO labeled MSCs and small groups of SPIO labeled MSCs in brain tissue and can be appropriate for monitoring migration and homing of transplanted cells in basic and translational neuroscience.

  20. Melatonin-induced methylation of the ABCG2/BCRP promoter as a novel mechanism to overcome multidrug resistance in brain tumour stem cells

    OpenAIRE

    Martín, V.; Sanchez-Sanchez, A M; Herrera, F.; Gomez-Manzano, C; Fueyo, J; Alvarez-Vega, M A; Antolín, I; Rodriguez, C.

    2013-01-01

    Background: Current evidence indicates that a stem cell-like sub-population within malignant glioblastomas, that overexpress members of the adenosine triphosphate-binding cassette (ABC) family transporters, is responsible for multidrug resistance and tumour relapse. Eradication of the brain tumour stem cell (BTSC) compartment is therefore essential to achieve a stable and long-lasting remission. Methods: Melatonin actions were analysed by viability cell assays, flow cytometry, quantitative PC...

  1. Activation of RARα, RARγ, or RXRα Increases Barrier Tightness in Human Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells.

    Science.gov (United States)

    Stebbins, Matthew J; Lippmann, Ethan S; Faubion, Madeline G; Daneman, Richard; Palecek, Sean P; Shusta, Eric V

    2017-09-28

    The blood-brain barrier (BBB) is critical to central nervous system (CNS) health. Brain microvascular endothelial cells (BMECs) are often used as in vitro BBB models for studying BBB dysfunction and therapeutic screening applications. Human pluripotent stem cells (hPSCs) can be differentiated to cells having key BMEC barrier and transporter properties, offering a renewable, scalable source of human BMECs. hPSC-derived BMECs have previously been shown to respond to all-trans retinoic acid (RA), and the goal of this study was to identify the stages at which differentiating human induced pluripotent stem cells (iPSCs) respond to activation of RA receptors (RARs) to impart BBB phenotypes. Here the authors identified that RA application to iPSC-derived BMECs at days 6-8 of differentiation led to a substantial elevation in transendothelial electrical resistance and induction of VE-cadherin expression. Specific RAR agonists identified RARα, RARγ, and RXRα as receptors capable of inducing barrier phenotypes. Moreover, RAR/RXRα costimulation elevated VE-cadherin expression and improved barrier fidelity to levels that recapitulated the effects of RA. This study elucidates the roles of RA signaling in iPSC-derived BMEC differentiation, and identifies directed agonist approaches that can improve BMEC fidelity for drug screening studies while also distinguishing potential nuclear receptor targets to explore in BBB dysfunction and therapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Heterotopically transplanted CVO neural stem cells generate neurons and migrate with SVZ cells in the adult mouse brain.

    Science.gov (United States)

    Bennett, Lori B; Cai, Jingli; Enikolopov, Grigori; Iacovitti, Lorraine

    2010-05-07

    Production of new neurons throughout adulthood has been well characterized in two brain regions, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus. The neurons produced from these regions arise from neural stem cells (NSCs) found in highly regulated stem cell niches. We recently showed that midline structures called circumventricular organs (CVOs) also contain NSCs capable of neurogenesis and/or astrogliogenesis in vitro and in situ (Bennett et al.). The present study demonstrates that NSCs derived from two astrogliogenic CVOs, the median eminence and organum vasculosum of the lamina terminalis of the nestin-GFP mouse, possess the potential to integrate into the SVZ and differentiate into cells with a neuronal phenotype. These NSCs, following expansion and BrdU-labeling in culture and heterotopic transplantation into a region proximal to the SVZ in adult mice, migrate caudally to the SVZ and express early neuronal markers (TUC-4, PSA-NCAM) as they migrate along the rostral migratory stream. CVO-derived BrdU(+) cells ultimately reach the olfactory bulb where they express early (PSA-NCAM) and mature (NeuN) neuronal markers. Collectively, these data suggest that although NSCs derived from the ME and OVLT CVOs are astrogliogenic in situ, they produce cells phenotypic of neurons in vivo when placed in a neurogenic environment. These findings may have implications for neural repair in the adult brain. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  4. Human skin-derived stem cells migrate throughout forebrain and differentiate into astrocytes after injection into adult mouse brain.

    Science.gov (United States)

    Belicchi, Marzia; Pisati, Federica; Lopa, Raffaella; Porretti, Laura; Fortunato, Francesco; Sironi, Manuela; Scalamogna, Mario; Parati, Eugenio A; Bresolin, Nereo; Torrente, Yvan

    2004-08-15

    Recent evidence indicates that neural stem cell properties can be found among a mammalian skin-derived multipotent population. A major barrier in the further characterization of the human skin-derived neural progenitors is the inability to isolate this population based on expression of cell surface markers. Our work has been devoted to purified human skin-derived stem cells that are capable of neural differentiation, based on the presence or absence of the AC133 cell surface marker. The enriched skin-derived AC133(+) cells express the CD34 and Thy-1 antigens. These cells cultured in a growth medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) proliferate, forming spheres, and differentiate in vitro into neurons, astrocytes, and rarely into oligodendrocytes. Single cells from sphere cultures initiated from human purified AC133(+) cells were replated as single cells and were able to generate new spheres, demonstrating the self-renewing ability of these stem cell populations. Brain engraftment of cells obtained from human purified AC133(+)-derived spheres generated different neural phenotypes: immature neurons and a most abundant population of well differentiated astrocytes. The AC133-derived astrocytes assumed perivascular locations in the frontal cortex. No donor-derived oligodendrocytes were found in the transplanted mouse brains. Several donor small, rounded cells that expressed endothelial markers were found close to the host vessel and near the subventricular zone. Thus, mammalian skin AC133-derived cells behave as a multipotent population with the capacity to differentiate into neural lineages in vitro and, prevalently, endothelium and astrocytes in vivo, demonstrating the great plasticity of these cells and suggesting potential clinical application. Copyright 2004 Wiley-Liss, Inc.

  5. Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach.

    Science.gov (United States)

    Nih, Lina R; Moshayedi, Pouria; Llorente, Irene L; Berg, Andrew R; Cinkornpumin, Jessica; Lowry, William E; Segura, Tatiana; Carmichael, S Thomas

    2017-02-01

    This article presents data related to the research article "Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain" (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016) [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA)-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs) after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1) Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2) the use of a design of Experiment (DOE) approach (M.W. 2 Weible and T. Chan-Ling, 2007) [2] to select multi-factorial experimental conditions, and (3) Inflammatory response and cell survival after transplantation.

  6. Bringing CLARITY to Gray Matter Atrophy

    Science.gov (United States)

    Spence, Rory D.; Kurth, Florian; Itoh, Noriko; Mongerson, Chandler R.L.; Wailes, Shannon H.; Peng, Mavis S.; MacKenzie-Graham, Allan J.

    2015-01-01

    Gray matter atrophy has been shown to be a strong correlate to clinical disability in multiple sclerosis (MS) and its most commonly used animal model, experimental autoimmune encephalomyelitis (EAE). However, the relationship between gray mater atrophy and the spinal cord pathology often observed in EAE has never been established. Here EAE was induced in Thy1.1-YFP mice and their brains imaged using in vivo magnetic resonance imaging (MRI). The brains and spinal cords were subsequently optically cleared using Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging-compatible Tissue-hYdrogel (CLARITY). Axons were followed 5 mm longitudinally in three dimensions in intact spinal cords revealing that 61% of the axons exhibited a mean of 22 axonal ovoids and 8% of the axons terminating in axonal end bulbs. In the cerebral cortex, we observed a decrease in the mean number of layer V pyramidal neurons and a decrease in the mean length of the apical dendrites of the remaining neurons, compared to healthy controls. MRI analysis demonstrated decreased cortical volumes in EAE. Cross-modality correlations revealed a direct relationship between cortical volume loss and axonal end bulb number in the spinal cord, but not ovoid number. This is the first report of the use of CLARITY in an animal model of disease and the first report of the use of both CLARITY and MRI. PMID:25038439

  7. Persistent facial myokymia: a rare pathognomic physical sign of intrinsic brain-stem lesions: report of 2 cases and review of literature.

    Directory of Open Access Journals (Sweden)

    Sharma R

    1992-01-01

    Full Text Available Characteristically continuous facial myokymia is a pathognomonic, exceedingly rare physical sign of intrinsic brain-stem lesions e.g. multiple sclerosis (where the myokymia lasts only for a few months, pontine glioma (where it is unremitting for years. The physiopathogenesis is unclear. Electromyographic patterns are characteristic. Therapy and prognosis are related to the basic aetio-pathological process. Only two out of 132 cases of intrinsic brain-stem lesions in the department of Neurosurgery, Seth G.s. Medical College, Bombay over a period of 3 decades, exemplify its rarity. These two cases are reported here and the relevant literature is reviewed.

  8. Spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    D'Amico Adele

    2011-11-01

    Full Text Available Abstract Spinal muscular atrophy (SMA is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Estimated incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 1/40-1/60. This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV based on age of onset and motor function achieved. This disease is caused by homozygous mutations of the survival motor neuron 1 (SMN1 gene, and the diagnostic test demonstrates in most patients the homozygous deletion of the SMN1 gene, generally showing the absence of SMN1 exon 7. The test achieves up to 95% sensitivity and nearly 100% specificity. Differential diagnosis should be considered with other neuromuscular disorders which are not associated with increased CK manifesting as infantile hypotonia or as limb girdle weakness starting later in life. Considering the high carrier frequency, carrier testing is requested by siblings of patients or of parents of SMA children and are aimed at gaining information that may help with reproductive planning. Individuals at risk should be tested first and, in case of testing positive, the partner should be then analyzed. It is recommended that in case of a request on carrier testing on siblings of an affected SMA infant, a detailed neurological examination should be done and consideration given doing the direct test to exclude SMA. Prenatal diagnosis should be offered to couples who have previously had a child affected with SMA (recurrence risk 25%. The role of follow-up coordination has to be managed by an expert in neuromuscular disorders and in SMA who is able to plan a multidisciplinary intervention that includes pulmonary, gastroenterology/nutrition, and orthopedic care. Prognosis

  9. Magnetic Resonance Imaging of Ferumoxytol-Labeled Human Mesenchymal Stem Cells in the Mouse Brain.

    Science.gov (United States)

    Lee, Na Kyung; Kim, Hyeong Seop; Yoo, Dongkyeom; Hwang, Jung Won; Choi, Soo Jin; Oh, Wonil; Chang, Jong Wook; Na, Duk L

    2017-02-01

    The success of stem cell therapy is highly dependent on accurate delivery of stem cells to the target site of interest. Possible ways to track the distribution of MSCs in vivo include the use of reporter genes or nanoparticles. The U.S. Food and Drug Administration (FDA) has approved ferumoxytol (Feraheme® [USA], Rienso® [UK]) as a treatment for iron deficiency anemia. Ferumoxytol is an ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) that has recently been used to track the fate of transplanted cells using magnetic resonance imaging (MRI). The major objectives of this study were to demonstrate the feasibility of labeling hUCB-MSCs with ferumoxytol and to observe, through MRI, the engraftment of ferumoxytol-labeled human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) delivered via stereotactic injection into the hippocampi of a transgenic mouse model of familial Alzheimer's disease (5XFAD). Ferumoxytol had no toxic effects on the viability or stemness of hUCB-MSCs when assessed in vitro. Through MRI, hypointense signals were discernible at the site where ferumoxytol-labeled human MSCs were injected. Iron-positive areas were also observed in the engrafted hippocampi. The results from this study support the use of nanoparticle labeling to monitor transplanted MSCs in real time as a follow-up for AD stem cell therapy in the clinical field.

  10. An isogenic blood-brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells.

    Science.gov (United States)

    Canfield, Scott G; Stebbins, Matthew J; Morales, Bethsymarie Soto; Asai, Shusaku W; Vatine, Gad D; Svendsen, Clive N; Palecek, Sean P; Shusta, Eric V

    2017-03-01

    The blood-brain barrier (BBB) is critical in maintaining a physical and metabolic barrier between the blood and the brain. The BBB consists of brain microvascular endothelial cells (BMECs) that line the brain vasculature and combine with astrocytes, neurons and pericytes to form the neurovascular unit. We hypothesized that astrocytes and neurons generated from human-induced pluripotent stem cells (iPSCs) could induce BBB phenotypes in iPSC-derived BMECs, creating a robust multicellular human BBB model. To this end, iPSCs were used to form neural progenitor-like EZ-spheres, which were in turn differentiated to neurons and astrocytes, enabling facile neural cell generation. The iPSC-derived astrocytes and neurons induced barrier tightening in primary rat BMECs indicating their BBB inductive capacity. When co-cultured with human iPSC-derived BMECs, the iPSC-derived neurons and astrocytes significantly elevated trans-endothelial electrical resistance, reduced passive permeability, and improved tight junction continuity in the BMEC cell population, while p-glycoprotein efflux transporter activity was unchanged. A physiologically relevant neural cell mixture of one neuron: three astrocytes yielded optimal BMEC induction properties. Finally, an isogenic multicellular BBB model was successfully demonstrated employing BMECs, astrocytes, and neurons from the same donor iPSC source. It is anticipated that such an isogenic facsimile of the human BBB could have applications in furthering understanding the cellular interplay of the neurovascular unit in both healthy and diseased humans. Read the Editorial Highlight for this article on page 843. © 2016 International Society for Neurochemistry.

  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......-neuropathic patients and in 16 individually matched control subjects. In the neuropathic patients the muscle strength of the ankle dorsal and plantar flexors was reduced by 41 % as compared to the non-neuropathic patients (p ... 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. Multiple system atrophy.

    Science.gov (United States)

    Peeraully, Tasneem

    2014-04-01

    Multiple system atrophy (MSA) is a rare adult-onset synucleinopathy associated with dysautonomia and the variable presence of poorly levodopa-responsive parkinsonism and/or cerebellar ataxia. Other clinical symptoms that can be associated with MSA include hyperreflexia, stridor, sleep apnea, and rapid eye movement sleep behavior disorder (RBD). Mean survival from time of diagnosis ranges between 6 to 10 years, and definitive diagnosis is made on autopsy with demonstration of oligodendroglial cytoplasmic inclusions consisting of fibrillar α-synuclein. Magnetic resonance imaging (MRI) may be positive for cruciform T2 hyperintensity within the pons (the "hot cross bun sign"), volume loss in the pons and cerebellum, and T2 signal loss in the dorsolateral putamen with hyperintense rim on fluid attenuated inversion recovery (FLAIR) sequencing. Although most cases are sporadic, genetic polymorphisms have been identified both in familial and sporadic cases of MSA, and influence observed phenotypes. Treatment is symptomatic, with both pharmacological and nonpharmacological strategies. There are currently no consensus guidelines on management. Current and future research is aimed at identifying biomarkers and developing disease-modifying therapies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Posterior cortical atrophy.

    Science.gov (United States)

    Zakzanis, K K; Boulos, M I

    2001-11-01

    The term posterior cortical atrophy (PCA) was introduced in 1988 to describe five patients with fairly homogeneous, but otherwise unclassified, symptoms. These patients showed signs of a slowly progressive dementia bearing behavioral and physiologic similarities to Alzheimer's disease, but with notable distinctions. Specifically, PCA is characterized by an early onset of visual agnosia, followed by some or all components of Balint's syndrome, Gerstmann's syndrome, and transcortical sensory aphasia. In this review, the history, epidemiology, pathophysiology, neurobehavioral aspects, assessment (including neurologic and neuropsychologic), differential diagnosis, and treatment recommendations for this disorder are reviewed. As originally defined, PCA appears to be a clinically homogeneous syndrome. The cluster of symptoms that are common to virtually all examined cases evidences this. Although the behavioral and cognitive properties of the disorder are well established, many aspects of PCA remain unclear. Specifically, available research and understanding of PCA epidemiology and treatment are highly inadequate. In fact, the majority of such information regarding PCA is derived from studies of Alzheimer's disease. To a lesser extent, Pick's disease and Creutzfeldt-Jakob disease research have also provided insight into the underpinnings of PCA. Until PCA is categorically defined as a variant or subgroup of these other neurodegenerative disorders, however, such derivations are merely speculations.

  14. [Macular atrophy in Terson's syndrome].

    Science.gov (United States)

    Sánchez-Vicente, J L; Frau-Aguilera, L; Sánchez-Vicente, P; Herrador-Montiel, A; Rueda-Rueda, T; Castilla-Lázpita, A; Romera-Piñero, A; Medina-Tapia, A

    2015-01-01

    The case is presented on a 63-year-old patient with Terson's syndrome who complained of loss of visual acuity. The optical coherence tomography showed macular atrophy. The patient developed macular atrophy probably secondary to macular hemorrhage caused by the rupture of a cerebral aneurysm. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  15. c-myc and N-myc promote active stem cell metabolism and cycling as architects of the developing brain.

    Science.gov (United States)

    Wey, Alice; Knoepfler, Paul S

    2010-06-01

    myc genes are associated with a wide variety of human cancers including most types of nervous system tumors. While the mechanisms by which myc overexpression causes tumorigenesis are multifaceted and have yet to be clearly elucidated, they are at least in part related to endogenous myc function in normal cells. Knockout (KO) of either c-myc or N-myc genes in neural stem and precursor cells (NSC) driven by nestin-cre impairs mouse brain growth and mutation of N-myc also causes microcephaly in humans in Feingold Syndrome. To further define myc function in NSC and nervous system development, we created a double KO (DKO) for c- and N-myc using nestin-cre. The DKO mice display profoundly impaired overall brain growth associated with decreased cell cycling and migration of NSC, which are strikingly decreased in number. The DKO brain also exhibits specific changes in gene expression including downregulation of genes involved in protein and nucleotide metabolism, mitosis, and chromatin structure as well as upregulation of genes associated with differentiation. Together these data support a model of nervous system tumorigenesis in which excess myc aberrantly locks in a developmentally active chromatin state characterized by overactive cell cycling, and metabolism as well as blocked differentiation.

  16. 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.

  17. Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain.

    Science.gov (United States)

    Yamaguchi, Masahiro; Seki, Tatsunori; Imayoshi, Itaru; Tamamaki, Nobuaki; Hayashi, Yoshitaka; Tatebayashi, Yoshitaka; Hitoshi, Seiji

    2016-05-01

    Neurons and glia in the central nervous system (CNS) originate from neural stem cells (NSCs). Knowledge of the mechanisms of neuro/gliogenesis from NSCs is fundamental to our understanding of how complex brain architecture and function develop. NSCs are present not only in the developing brain but also in the mature brain in adults. Adult neurogenesis likely provides remarkable plasticity to the mature brain. In addition, recent progress in basic research in mental disorders suggests an etiological link with impaired neuro/gliogenesis in particular brain regions. Here, we review the recent progress and discuss future directions in stem cell and neuro/gliogenesis biology by introducing several topics presented at a joint meeting of the Japanese Association of Anatomists and the Physiological Society of Japan in 2015. Collectively, these topics indicated that neuro/gliogenesis from NSCs is a common event occurring in many brain regions at various ages in animals. Given that significant structural and functional changes in cells and neural networks are accompanied by neuro/gliogenesis from NSCs and the integration of newly generated cells into the network, stem cell and neuro/gliogenesis biology provides a good platform from which to develop an integrated understanding of the structural and functional plasticity that underlies the development of the CNS, its remodeling in adulthood, and the recovery from diseases that affect it.

  18. Paving the way towards complex blood-brain barrier models using pluripotent stem cells

    DEFF Research Database (Denmark)

    Lauschke, Karin; Frederiksen, Lise; Hall, Vanessa Jane

    2017-01-01

    A tissue with great need to be modelled in vitro is the blood-brain barrier (BBB). The BBB is a tight barrier that covers all blood vessels in the brain and separates the brain microenvironment from the blood system. It consists of three cell types (neurovascular unit (NVU)) that contribute......, it is now possible to produce many cell types from the BBB and even partially recapitulate this complex tissue in vitro. In this review, we summarize the most recent developments in PSC differentiation and modelling of the BBB. We also suggest how patient-specific human induced PSCs could be used to model...

  19. Development and Characterization of a Brain Endothelial Cell Phenotype using Human Induced Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Holst, Bjørn

    be used to investigate drug transport in vitro, and screen candidates for permeation properties. One recent approach is to develop in vitro models of the BBB using human induced pluripotent stem cells (hIPSCs) as described by Stebbins et al. (2015).The aim of the present study was to investigate whether...

  20. Assessment of long-term safety and efficacy of intranasal mesenchymal stem cell treatment for neonatal brain injury in the mouse

    NARCIS (Netherlands)

    Donega, Vanessa; Nijboer, Cora H.A.; Van Velthoven, Cindy T J; Youssef, Sameh A.; De Bruin, Alain; Van Bel, Frank; Kavelaars, Annemieke; Heijnen, Cobi J.; Nijboer, CHA

    2015-01-01

    Background:For clinical translation, we assessed whether intranasal mesenchymal stem cell (MSC) treatment after hypoxia-ischemia (HI) induces neoplasia in the brain or periphery at 14 mo. Furthermore, the long-term effects of MSCs on behavior and lesion size were determined.Method:HI was induced in

  1. In vivo Brain Delivery of v-myc Overproduced Human Neural Stem Cells via the Intranasal Pathway: Tumor Characteristics in the Lung of a Nude Mouse

    Directory of Open Access Journals (Sweden)

    Eun Seong Lee

    2015-01-01

    Full Text Available We aimed to monitor the successful brain delivery of stem cells via the intranasal route and to observe the long-term consequence of the immortalized human neural stem cells in the lungs of a nude mouse model. Stably immortalized HB1.F3 human neural stem cells with firefly luciferase gene (F3-effluc were intranasally delivered to BALB/c nude mice. Bioluminescence images were serially acquired until 41 days in vivo and at 4 hours and 41 days ex vivo after intranasal delivery. Lungs were evaluated by histopathology. After intranasal delivery of F3-effluc cells, the intense in vivo signals were detected in the nasal area, migrated toward the brain areas at 4 hours (4 of 13, 30.8%, and gradually decreased for 2 days. The brain signals were confirmed by ex vivo imaging (2 of 4, 50%. In the mice with initial lung signals (4 of 9, 44.4%, the lung signals disappeared for 5 days but reappeared 2 weeks later. The intense lung signals were confirmed to originate from the tumors in the lungs formed by F3-effluc cells by ex vivo imaging and histopathology. We propose that intranasal delivery of immortalized stem cells should be monitored for their successful delivery to the brain and their tumorigenicity longitudinally.

  2. Quiescence and activation of stem and precursor cell populations in the subependymal zone of the mammalian brain are associated with distinct cellular and extracellular matrix signals

    Science.gov (United States)

    The subependymal zone (SEZ) of the lateral ventricles is one of the areas of the adult brain where new neurons are continuously generated from neural stem cells (NSCs), via rapidly dividing precursors. This neurogenic niche is a complex cellular and extracellular microenvironment, highly vascularize...

  3. Nop2 is expressed during proliferation of neural stem cells and in adult mouse and human brain.

    Science.gov (United States)

    Kosi, Nina; Alić, Ivan; Kolačević, Matea; Vrsaljko, Nina; Jovanov Milošević, Nataša; Sobol, Margarita; Philimonenko, Anatoly; Hozák, Pavel; Gajović, Srećko; Pochet, Roland; Mitrečić, Dinko

    2015-02-09

    The nucleolar protein 2 gene encodes a protein specific for the nucleolus. It is assumed that it plays a role in the synthesis of ribosomes and regulation of the cell cycle. Due to its link to cell proliferation, higher expression of Nop2 indicates a worse tumor prognosis. In this work we used Nop2(gt1gaj) gene trap mouse strain. While lethality of homozygous animals suggested a vital role of this gene, heterozygous animals allowed the detection of expression of Nop2 in various tissues, including mouse brain. Histochemistry, immunohistochemistry and immunoelectron microscopy techniques, applied to a mature mouse brain, human brain and on mouse neural stem cells revealed expression of Nop2 in differentiating cells, including astrocytes, as well as in mature neurons. Nop2 was detected in various regions of mouse and human brain, mostly in large pyramidal neurons. In the human, Nop2 was strongly expressed in supragranular and infragranular layers of the somatosensory cortex and in layer III of the cingulate cortex. Also, Nop2 was detected in CA1 and the subiculum of the hippocampus. Subcellular analyses revealed predominant location of Nop2 within the dense fibrillar component of the nucleolus. To test if Nop2 expression correlates to cell proliferation occurring during tissue regeneration, we induced strokes in mice by middle cerebral artery occlusion. Two weeks after stroke, the number of Nop2/nestin double positive cells in the region affected by ischemia and the periventricular zone substantially increased. Our findings suggest a newly discovered role of Nop2 in both mature neurons and in cells possibly involved in the regeneration of nervous tissue. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Mesenchymal stem cells induce T-cell tolerance and protect the preterm brain after global hypoxia-ischemia.

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    Reint K Jellema

    Full Text Available Hypoxic-ischemic encephalopathy (HIE in preterm infants is a severe disease for which no curative treatment is available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play a pivotal role in the etiology of white matter injury, which is the clinical hallmark of HIE in preterm infants. The objective of this study was to assess the neuroprotective and anti-inflammatory effects of intravenously delivered mesenchymal stem cells (MSC in an ovine model of HIE. In this translational animal model, global hypoxia-ischemia (HI was induced in instrumented preterm sheep by transient umbilical cord occlusion, which closely mimics the clinical insult. Intravenous administration of 2 x 10(6 MSC/kg reduced microglial proliferation, diminished loss of oligodendrocytes and reduced demyelination, as determined by histology and Diffusion Tensor Imaging (DTI, in the preterm brain after global HI. These anti-inflammatory and neuroprotective effects of MSC were paralleled by reduced electrographic seizure activity in the ischemic preterm brain. Furthermore, we showed that MSC induced persistent peripheral T-cell tolerance in vivo and reduced invasion of T-cells into the preterm brain following global HI. These findings show in a preclinical animal model that intravenously administered MSC reduced cerebral inflammation, protected against white matter injury and established functional improvement in the preterm brain following global HI. Moreover, we provide evidence that induction of T-cell tolerance by MSC might play an important role in the neuroprotective effects of MSC in HIE. This is the first study to describe a marked neuroprotective effect of MSC in a translational animal model of HIE.

  5. [Homonymous hemianopia and posterior cortical atrophy].

    Science.gov (United States)

    Formaglio, M; Krolak-Salmon, P; Tilikete, C; Bernard, M; Croisile, B; Vighetto, A

    2009-03-01

    Posterior cortical atrophy (PCA) is a clinically and radiologically defined syndrome, in which predominant symptoms focus on higher visual dysfunction with progressive course and association with cortical atrophy or hypometabolism that predominates in the posterior part of the hemispheres. Homonymous hemianopia (HH) has rarely been described in this syndrome. We report on six patients (four females, two males, aged 63 to 80) referred for visual disorder which led to demonstration of HH using perimetry testing. These patients were followed for 1 to 5 years after discovery of HH. Brain imaging with MRI or CT scan was obtained in the six cases and a SPECT scan was performed in four cases. HH was left-sided in four cases and right-sided in two cases. Associated symptoms related to higher visual dysfunction were simultagnosia, alone or as part of a full Balint's syndrome, alexia, constructional apraxia, dressing apraxia, visual form agnosia, prosopagnosia and hemispatial neglect. These symptoms were mild at onset but invariably worsened with disease progression. Dementia eventually developed in all cases. The clinical diagnosis was probable Alzheimer's disease in five cases and corticobasal degeneration in one case. Radiology showed posterior cortex atrophy in all cases as well as reduced cerebral blood flow in the same region, with an asymmetrical pattern compatible with the side of HH. Elementary cortical lesions in PCA can develop mainly in the associative visual areas and even in the primary visual area, resulting in HH. HH has rarely been documented in PCA, but its prevalence would probably be higher if systematic search was conducted. Apparently isolated HH of insidious onset should suggest PCA and lead to neuropsychological testing and search for discrete atrophic changes of the posterior cortex on MRI as well as for metabolic alterations with SPECT or PET.

  6. Electroresponsive properties and membrane potential trajectories of three types of inspiratory neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Champagnat, J; Denavit-Saubié, M

    1996-01-01

    with the aim of extending the classification of inspiratory neurons to include analysis of active membrane properties. 2. The slice generated a regular rhythmic motor output recorded as burst of action potentials on a XII nerve root with a peak to peak time of 11.5 +/- 3.4 s and a duration of 483 +/- 54 ms......1. The electrophysiological properties of inspiratory neurons were studied in a rhythmically active thick-slice preparation of the newborn mouse brain stem maintained in vitro. Whole cell patch recordings were performed from 60 inspiratory neurons within the rostral ventrolateral part of the slice...... (means +/- SD, n = 50). Based on the electroresponsive properties and membrane potential trajectories throughout the respiratory cycle, three types of inspiratory neurons could be distinguished. 3. Type-1 neurons were spiking in the interval between the inspiratory potentials (n = 9) or silent...

  7. Blindness, dancing extremities, and corpus callosum and brain stem involvement: an unusual presentation of fulminant subacute sclerosing panencephalitis.

    Science.gov (United States)

    Singhi, Pratibha; Saini, Arushi Gahlot; Sankhyan, Naveen; Gupta, Pankaj; Vyas, Sameer

    2015-01-01

    A 4-year-old girl presented with acute visual loss followed 2 weeks later with loss of speech and audition, fulminant neuroregression, and choreo-athetoid movements of extremities. Fundus showed bilateral chorioretinitis. Electroencephalography showed periodic complexes. Measles antibody titers were elevated in both serum and cerebrospinal fluid, consistent with subacute sclerosing panencephalitis. Neuroimaging showed discontiguous involvement of splenium of the corpus callosum and ventral pons with sparing of cortical white matter. Our case highlights the atypical clinical and radiologic presentations of subacute sclerosing panencephalitis. Pediatricians need to be aware that necrotizing chorioretinitis in a child and/or atypical brain stem changes could be the heralding feature of this condition in endemic countries. © The Author(s) 2014.

  8. Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Feldman, J L

    1997-01-01

    Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro. J. Neurophysiol. 78: 2483-2492, 1997. The nucleus ambiguus contains vagal and glossopharyngeal motoneurons and preganglionic neurons involved in respiration, swallowing, vocalization......, and control of heart beat. Here we show that the rostral compact formation's ambiguus neurons, which control the esophageal phase of swallowing, display calcium-dependent plateau potentials in response to tetanic orthodromic stimulation or current injection. Whole cell recordings were made from visualized...... neurons in the rostral nucleus ambiguus using a slice preparation from the newborn mouse. Biocytin-labeling revealed dendritic trees with pronounced rostrocaudal orientations confined to the nucleus ambiguus, a morphological profile matching that of vagal motoneurons projecting to the esophagus. Single...

  9. Assessment of Electrically Evoked Auditory Brain Stem Response of 30 Implanted Patients With Nucleus Multichannel Cochlear Implant

    Directory of Open Access Journals (Sweden)

    Dr. Soqrat Faghihzadeh

    2001-05-01

    Full Text Available Methods and Materials: Investigation of electrically evoked auditory brain stem response (EABR is a new issue, especially in implanted patients. Experiments were performed in C.I Center of Iranian Institute for Science and research expansion,1996 on 30 implanted patients with 22 spectra and MSP cochlear implant system and 30 normal subjects with the range of 3-33 years. Findings: I- EABR was obtained in the implanted patients. 2- Absolute latency of EABR waves is 1-1.5 ms shorter than ABR waves ‘P<0.05. 3-Absolute latency of wave V decreases as a function of electric stimulus magnitude (P<0.05. 4- No significant difference was observed in IPL Ill-V between ABR and EABR.

  10. Heme oxygenase-1 plays a pro-life role in experimental brain stem death via nitric oxide synthase I/protein kinase G signaling at rostral ventrolateral medulla

    Directory of Open Access Journals (Sweden)

    Dai Kuang-Yu

    2010-09-01

    Full Text Available Abstract Background Despite its clinical importance, a dearth of information exists on the cellular and molecular mechanisms that underpin brain stem death. A suitable neural substrate for mechanistic delineation on brain stem death resides in the rostral ventrolateral medulla (RVLM because it is the origin of a life-and-death signal that sequentially increases (pro-life and decreases (pro-death to reflect the advancing central cardiovascular regulatory dysfunction during the progression towards brain stem death in critically ill patients. The present study evaluated the hypothesis that heme oxygnase-1 (HO-1 may play a pro-life role as an interposing signal between hypoxia-inducible factor-1 (HIF-1 and nitric oxide synthase I (NOS I/protein kinase G (PKG cascade in RVLM, which sustains central cardiovascular regulatory functions during brain stem death. Methods We performed cardiovascular, pharmacological, biochemical and confocal microscopy experiments in conjunction with an experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol bilaterally into RVLM of adult male Sprague-Dawley rats. Results Western blot analysis coupled with laser scanning confocal microscopy revealed that augmented HO-1 expression that was confined to the cytoplasm of RVLM neurons occurred preferentially during the pro-life phase of experimental brain stem death and was antagonized by immunoneutralization of HIF-1α or HIF-1β in RVLM. On the other hand, the cytoplasmic presence of HO-2 in RVLM neurons manifested insignificant changes during both phases. Furthermore, immunoneutralization of HO-1 or knockdown of ho-1 gene in RVLM blunted the augmented life-and-death signals exhibited during the pro-life phase. Those pretreatments also blocked the upregulated pro-life NOS I/PKG signaling without affecting the pro-death NOS II/peroxynitrite cascade in RVLM. Conclusions We conclude that transcriptional

  11. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

    2015-10-01

    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  12. Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach

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    Lina R. Nih

    2017-02-01

    Full Text Available This article presents data related to the research article “Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain” (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016 [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1 Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2 the use of a design of Experiment (DOE approach (M.W. 2 Weible and T. Chan-Ling, 2007 [2] to select multi-factorial experimental conditions, and (3 Inflammatory response and cell survival after transplantation.

  13. Distribution and localization of fibroblast growth factor-8 in rat brain and nerve cells during neural stem/progenitor cell differentiation.

    Science.gov (United States)

    Lu, Jiang; Li, Dongsheng; Lu, Kehuan

    2012-07-05

    The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor, fibroblast growth factor receptor-3, in adult rat brain in vivo and in nerve cells during differentiation of neural stem/progenitor cells in vitro. Immunohistochemistry was used to examine the distribution of fibroblast growth factor-8 in adult rat brain in vivo. Localization of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in cells during neural stem/progenitor cell differentiation in vitro was detected by immunofluorescence. Flow cytometry and immunofluorescence were used to evaluate the effect of an anti-fibroblast growth factor-8 antibody on neural stem/progenitor cell differentiation and expansion in vitro. Results from this study confirmed that fibroblast growth factor-8 was mainly distributed in adult midbrain, namely the substantia nigra, compact part, dorsal tier, substantia nigra and reticular part, but was not detected in the forebrain comprising the caudate putamen and striatum. Unusual results were obtained in retrosplenial locations of adult rat brain. We found that fibroblast growth factor-8 and fibroblast growth factor receptor-3 were distributed on the cell membrane and in the cytoplasm of nerve cells using immunohistochemistry and immunofluorescence analyses. We considered that the distribution of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in neural cells corresponded to the characteristics of fibroblast growth factor-8, a secretory factor. Addition of an anti-fibroblast growth factor-8 antibody to cultures significantly affected the rate of expansion and differentiation of neural stem/progenitor cells. In contrast, addition of recombinant fibroblast growth factor-8 to differentiation medium promoted neural stem/progenitor cell differentiation and increased the final yields of dopaminergic neurons and total neurons. Our study may help delineate the important roles of fibroblast growth

  14. Neural stem cell transplantation in an animal model of traumatic brain injury.

    Science.gov (United States)

    Thomaidou, Dimitra

    2014-01-01

    The central nervous system (CNS) can be damaged by a wide range of conditions resulting in loss of specific populations of neurons and/or glial cells and in the development of defined psychiatric or neurological symptoms of varying severity. As the CNS has limited inherent capacity to regenerate lost tissue and self-repair, the development of therapeutic strategies for the treatment of CNS insults remains a serious scientific challenge with potential important clinical applications. In this context, strategies involving transplantation of specific cell populations, such as stem cells and neural stem cells (NSCs), to replace damaged cells offers an opportunity for the development of cell-based therapies. Along these lines, in this review we describe a protocol which involves transplantation of NPCs, genetically engineered to overexpress the neurogenic molecule Cend1 and have thus the potency to differentiate with higher frequency towards the neuronal lineage in a rodent model of stab wound cortical injury.

  15. Optimization of the magnetic labeling of human neural stem cells and MRI visualization in the hemiparkinsonian rat brain.

    Science.gov (United States)

    Ramos-Gómez, Milagros; Seiz, Emma G; Martínez-Serrano, Alberto

    2015-03-05

    Magnetic resonance imaging is the ideal modality for non-invasive in vivo cell tracking allowing for longitudinal studies over time. Cells labeled with superparamagnetic iron oxide nanoparticles have been shown to induce sufficient contrast for in vivo magnetic resonance imaging enabling the in vivo analysis of the final location of the transplanted cells. For magnetic nanoparticles to be useful, a high internalization efficiency of the particles is required without compromising cell function, as well as validation of the magnetic nanoparticles behaviour inside the cells. In this work, we report the development, optimization and validation of an efficient procedure to label human neural stem cells with commercial nanoparticles in the absence of transfection agents. Magnetic nanoparticles used here do not affect cell viability, cell morphology, cell differentiation or cell cycle dynamics. Moreover, human neural stem cells progeny labeled with magnetic nanoparticles are easily and non-invasively detected long time after transplantation in a rat model of Parkinson's disease (up to 5 months post-grafting) by magnetic resonance imaging. These findings support the use of commercial MNPs to track cells for short- and mid-term periods after transplantation for studies of brain cell replacement therapy. Nevertheless, long-term MR images should be interpreted with caution due to the possibility that some MNPs may be expelled from the transplanted cells and internalized by host microglial cells.

  16. Cord atrophy separates early primary progressive and relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Bieniek, M; Altmann, D R; Davies, G R; Ingle, G T; Rashid, W; Sastre-Garriga, J; Thompson, A J; Miller, D H

    2006-09-01

    The onset of multiple sclerosis is relapsing remitting or primary progressive. An improved understanding of the causes of early progressive disability in primary progressive multiple sclerosis (PPMS) could provide mechanistic targets for therapeutic intervention. Five magnetic resonance imaging (MRI) parameters that could potentially cause progressive disability were investigated in 43 patients with early PPMS and in 37 patients with early relapsing remitting multiple sclerosis (RRMS): atrophy in brain, both grey matter and white matter; intrinsic abnormality in brain, both grey matter and white matter (measured by the magnetisation transfer ratio (MTR)); and atrophy of the upper cervical spinal cord. Both groups were also compared with controls. Patients with PPMS were older and more likely to be men. Both patient groups had atrophy of brain grey matter and white matter, and intrinsic abnormality in MTR of normal-appearing grey matter and white matter. Cord atrophy was present only in the PPMS (mean cord area: PPMS, 67.8 mm2; RRMS, 72.7 mm2; controls, 73.4 mm2; p = 0.007). This was confirmed by multivariate analysis of all five MRI parameters, age and sex. Grey matter and white matter of the brain are abnormal in both early RRMS and PPMS, but cord atrophy is present only in PPMS. This is concordant with myelopathy being the usual clinical presentation of PPMS. Measurement of cord atrophy seems to be clinically relevant in PPMS treatment trials.

  17. Controlling micro- and nano-environment of tumor and stem cells for novel research and therapy of brain cancer

    Science.gov (United States)

    Smith, Christopher Lloyd

    The use of modern technologies in cancer research has engendered a great deal of excitement. Many of these advanced approaches involve in-depth mathematical analyses of the inner working of cells, via genomic and proteomic analyses. However these techniques may not be ideal for the study of complex cell phenotypes and behaviors. This dissertation explores cancer and potential therapies through phenotypic analysis of cell behaviors, an alternative approach. We employ this experimental framework to study brain cancer (glioma), a particularly formidable example of this diverse ailment. Through the application of micro- and nanotechnology, we carefully control the surrounding environments of cells to understand their responses to various cues and to manipulate their behaviors. Subsequently we obtain clinically relevant information that allows better understanding of glioma, and enhancement of potential therapies. We first aim to address brain tumor dispersal, through analysis of cell migration. Utilizing nanometer-scale topographic models of the extracellular matrix, we study the migratory response of glioma cells to various stimuli in vitro. Second, we implement knowledge gained from these investigations to define characteristics of tumor progression in patients, and to develop treatments inhibiting cell migration. Next we use microfluidic and nanotopographic models to study the behaviors of stem cells in vitro. Here we attempt to improve their abilities to deliver therapeutic proteins to cancer, an innovative treatment approach. We analyze the multi-step process by which adipose-derived stem cells naturally home to tumor sites, and identify numerous environmental perturbations to enhance this behavior. Finally, we attempt to demonstrate that these cell culture-based manipulations can enhance the localization of adipose stem cells to glioma in vivo using animal models. Throughout this work we utilize environmental cues to analyze and induce particular behaviors in

  18. Changes in host blood factors and brain glia accompanying the functional recovery after systemic administration of bone marrow stem cells in ischemic stroke rats.

    Science.gov (United States)

    Yang, Ming; Wei, Xiaotao; Li, Jing; Heine, Lynn A; Rosenwasser, Robert; Iacovitti, Lorraine

    2010-01-01

    In this study, we examined the effects of systemic administration of rat or human bone marrow stromal stem cells (MSC) at early and later times following middle cerebral artery occlusion (MCAO) on blood cytokines/growth factors, brain glia, and motor behavior in rats. Rats were tail vein injected with rat (r) and human (h) MSCs at 1 or 7 days post-MCAO. In some rats (N = 4) MSCs isolated from transgenic GFP rats were used to track the migration of cells peripherally and centrally at 2.5 and 28 days. Motor behavior was assessed using the modified Neurological Severity Score/climbing test at various time points before and after MCAO and transplantation. Prior to sacrifice at 1, 7, or 28 days post-MCAO, blood serum was collected for cytokine array analysis. Brains were analyzed for markers of activated microglia (CD11) and reactive astrocytes (GFAP). Administration of either allogeneic (rMSCs) or xenogeneic (hMSCs) stem cells produced a significant recovery of motor behavior after MCAO, with cells delivered at 1 day having greater effect than those at 7 days. Correlated with recovery was an amplification in activated microglia, reactive astrocytes, and new blood vessels in the infarct region, resulting in greater preservation in brain integrity. Concomitantly, expression of blood cytokines/chemokines (IL-13, MMP2, MIP) and growth factors/receptors (VEGF, neuropilin, EPOR, TROY, NGFR, RAGE) were modified following MSC administration. Because only rare GFP-labeled MSCs were observed in the brain, these effects did not depend on the central incorporation of stem cells. The early systemic administration of allogeneic or xenogeneic MSCs soon after experimental stroke produces a structural/functional recovery in the brain which is correlated with an increase in activated brain glia and changes in circulating cytokines and growth factors. Stem cells therefore induce an important neuroprotective and/or regenerative response in the host organism.

  19. Reduced 5-HT(1B) receptor binding in the dorsal brain stem after cognitive behavioural therapy of major depressive disorder.

    Science.gov (United States)

    Tiger, Mikael; Rück, Christian; Forsberg, Anton; Varrone, Andrea; Lindefors, Nils; Halldin, Christer; Farde, Lars; Lundberg, Johan

    2014-08-30

    Major depression is a significant contributor to the global burden of disease, and its pathophysiology is largely unknown. The serotonin hypothesis is, however, the model with most supporting data, although the details are only worked out to some extent. Recent clinical imaging measurements indeed imply a role in major depressive disorder (MDD) for the inhibitory serotonin autoreceptor 5-hydroxytryptamine1B (5-HT1B). The aim of the current study was to examine 5-HT1B receptor binding in the brain of MDD patients before and after psychotherapy. Ten patients with an ongoing untreated moderate depressive episode were examined with positron emission tomography (PET) and the 5-HT1B receptor selective radioligand [(11)C]AZ10419369, before and after treatment with internet-based cognitive behavioural therapy. All of the patients examined responded to treatment, and 70% were in remission by the time of the second PET measurement. A statistically significant 33% reduction of binding potential (BPND) was found in the dorsal brain stem (DBS) after treatment. No other significant changes in BPND were found. The DBS contains the raphe nuclei, which regulate the serotonin system. This study gives support for the importance of serotonin and the 5-HT1B receptor in the biological response to psychological treatment of MDD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Neural Stem Cell Delivery of Therapeutic Antibodies to Treat Breast Cancer Brain Metastases

    Science.gov (United States)

    2009-10-01

    conditions is promising ( 1 ) . Furthermore, it has previously 1. Introduction John S. Yu (ed.), Cancer Stem Cells, Methods in Molecular Biology, vol...D, Aucoin R, Blust J, Murry B, Greiter‐ Wilke  A: p75 neurotrophin receptor functions as a survival receptor in brain‐metastatic melanoma cells, J...domains. Nat Biotechnol 23(9): 1126-1136. (39) Colcher D, Pavlinkova G, Beresford G, Booth BJ, Choudhury A, Batra SK (1998) Pharmacokinetics and

  1. Effect of all-trans retinoic acid on the proliferation and differentiation of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Niu Chao

    2010-08-01

    Full Text Available Abstract Objective To investigate the effect of all-trans retinoic acid(ATRA on the proliferation and differentiation of brain tumor stem cells(BTSCs in vitro. Methods Limiting dilution and clonogenic assay were used to isolate and screen BTSCs from the fresh specimen of human brain glioblastoma. The obtained BTSCs, which were cultured in serum-free medium, were classified into four groups in accordance with the composition of the different treatments. The proliferation of the BTSCs was evaluated by MTT assay. The BTSCs were induced to differentiate in serum-containing medium, and classified into the ATRA group and control group. On the 10th day of induction, the expressions of CD133 and glial fibrillary acidic protein (GFAP in the differentiated BTSCs were detected by immunofluorescence. The differentiated BTSCs were cultured in serum-free medium, the percentage and the time required for formation of brain tumor spheres (BTS were observed. Results BTSCs obtained by limiting dilution were all identified as CD133-positive by immunofluorescence. In serum-free medium, the proliferation of BTSCs in the ATRA group was observed significantly faster than that in the control group, but slower than that in the growth factor group and ATRA/growth factor group, and the size of the BTS in the ATRA group was smaller than that in the latter two groups(P P P P Conclusion ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiation is incomplete, terminal differentiation cannot be achieved and BTSs can be formed again.

  2. Biological and clinical implications of cancer stem cells in primary brain tumors

    Directory of Open Access Journals (Sweden)

    Marcello eMaugeri-Saccà

    2013-01-01

    Full Text Available Despite therapeutic advances, glioblastoma multiforme (GBM remains a lethal disease. The infiltrative nature of this disease and the presence of a cellular population resistant to current medical treatments account for the poor prognosis of these patients. Growing evidence indicates the existence of a fraction of cancer cells sharing the functional properties of adult stem cells, including self-renewal and a greater ability to escape chemo-radiotherapy-induced death stimuli. Therefore, these cells are commonly defined as cancer stem cells (GBM-SCs. The initial GBM-SC concept has been challenged, and refined according to the emerging molecular taxonomy of GBM. This allowed to postulate the existence of multiple CSC types, each one driving a given molecular entity. Furthermore, it is becoming increasingly clear that GBM-SCs thrive through a dynamic and bidirectional interaction with the surrounding microenvironment. In this article, we discuss recent advances in GBM-SC biology, mechanisms through which these cells adapt to hostile conditions, pharmacological strategies for selectively killing GBM-SCs, and how novel CSC-associated endpoints have been investigated in the clinical setting.

  3. [Nocturnal stridor in multiple system atrophy

    NARCIS (Netherlands)

    Louter, M.; Pelleboer, R.H.; Broek, G.B. van den; Post, B.; Pevernagie, D.A.; Overeem, S.

    2011-01-01

    BACKGROUND: Multiple system atrophy is a neurodegenerative disorder with parkinsonism, cerebellar ataxia and autonomic dysfunction. The occurrence of nocturnal stridor in patients with multiple system atrophy is associated with a decreased life expectancy. This is what makes adequate treatment so

  4. A functional study of EGFR and Notch signaling in brain cancer stem-like cells from glioblastoma multiforme (Ph.d.)

    DEFF Research Database (Denmark)

    Kristoffersen, Karina

    2013-01-01

    for new molecular and cellular targets that can improve the prognosis for GBM patients. One such target is the brain cancer stem-like cells (bCSC) that are believed to be responsible for tumor initiation, progression, treatment resistance and ultimately relapse. bCSC are identified based...... treatment. The overall aim of the present PhD project has been to study the functional role of EGFR and Notch activity in bCSCs stem cell-like features and tumorigenic potential with the purpose of deepen our knowledge about the significance of these pathways in the bCSC population in GBM. By establishing...

  5. Autoimmune antibody decline in Parkinson's disease and Multiple System Atrophy; a step towards immunotherapeutic strategies

    DEFF Research Database (Denmark)

    Brudek, Tomasz; Winge, Kristian; Folke, Jonas

    2017-01-01

    BACKGROUND: Parkinson's' disease (PD) and Multiple System Atrophy (MSA) are progressive brain disorders characterized by intracellular accumulations of α-synuclein and nerve cell loss in specific brain areas. This loss causes problems with movement, balance and/or autonomic functions. Naturally...

  6. Evaluation of 18F-FDG PET and MRI associations in pediatric diffuse intrinsic brain stem glioma: a report from the Pediatric Brain Tumor Consortium.

    Science.gov (United States)

    Zukotynski, Katherine A; Fahey, Frederic H; Kocak, Mehmet; Alavi, Abass; Wong, Terence Z; Treves, S Ted; Shulkin, Barry L; Haas-Kogan, Daphne A; Geyer, Jeffrey R; Vajapeyam, Sridhar; Boyett, James M; Kun, Larry E; Poussaint, Tina Young

    2011-02-01

    The purpose of this study was to assess (18)F-FDG uptake in children with a newly diagnosed diffuse intrinsic brain stem glioma (BSG) and to investigate associations with progression-free survival (PFS), overall survival (OS), and MRI indices. Two Pediatric Brain Tumor Consortium (PBTC) therapeutic trials in children with newly diagnosed BSG were designed to test radiation therapy combined with molecularly targeted agents (PBTC-007: phase I/II study of gefitinib; PBTC-014: phase I/II study of tipifarnib). Baseline brain (18)F-FDG PET scans were obtained in 40 children in these trials. Images were evaluated by consensus between 2 PET experts for intensity and uniformity of tracer uptake. Associations of (18)F-FDG uptake intensity and uniformity with both PFS and OS, as well as associations with tumor MRI indices at baseline (tumor volume on fluid-attenuated inversion recovery, baseline intratumoral enhancement, diffusion and perfusion values), were evaluated. In most of the children, BSG (18)F-FDG uptake was less than gray-matter uptake. Survival was poor, irrespective of intensity of (18)F-FDG uptake, with no association between intensity of (18)F-FDG uptake and PFS or OS. However, hyperintense (18)F-FDG uptake in the tumor, compared with gray matter, suggested poorer survival rates. Patients with (18)F-FDG uptake in 50% or more of the tumor had shorter PFS and OS than did patients with (18)F-FDG uptake in less than 50% of the tumor. There was some evidence that tumors with higher (18)F-FDG uptake were more likely to show enhancement, and when the diffusion ratio was lower, the uniformity of (18)F-FDG uptake appeared higher. Children with BSG for which (18)F-FDG uptake involves at least half the tumor appear to have poorer survival than children with uptake in less than 50% of the tumor. A larger independent study is needed to verify this hypothesis. Intense tracer uptake in the tumors, compared with gray matter, suggests decreased survival. Higher (18)F-FDG uptake

  7. Long-term survival of human neural stem cells in the ischemic rat brain upon transient immunosuppression.

    Directory of Open Access Journals (Sweden)

    Laura Rota Nodari

    Full Text Available Understanding the physiology of human neural stem cells (hNSCs in the context of cell therapy for neurodegenerative disorders is of paramount importance, yet large-scale studies are hampered by the slow-expansion rate of these cells. To overcome this issue, we previously established immortal, non-transformed, telencephalic-diencephalic hNSCs (IhNSCs from the fetal brain. Here, we investigated the fate of these IhNSC's immediate progeny (i.e. neural progenitors; IhNSC-Ps upon unilateral implantation into the corpus callosum or the hippocampal fissure of adult rat brain, 3 days after global ischemic injury. One month after grafting, approximately one fifth of the IhNSC-Ps had survived and migrated through the corpus callosum, into the cortex or throughout the dentate gyrus of the hippocampus. By the fourth month, they had reached the ipsilateral subventricular zone, CA1-3 hippocampal layers and the controlateral hemisphere. Notably, these results could be accomplished using transient immunosuppression, i.e administering cyclosporine for 15 days following the ischemic event. Furthermore, a concomitant reduction of reactive microglia (Iba1+ cells and of glial, GFAP+ cells was also observed in the ipsilateral hemisphere as compared to the controlateral one. IhNSC-Ps were not tumorigenic and, upon in vivo engraftment, underwent differentiation into GFAP+ astrocytes, and β-tubulinIII+ or MAP2+ neurons, which displayed GABAergic and GLUTAmatergic markers. Electron microscopy analysis pointed to the formation of mature synaptic contacts between host and donor-derived neurons, showing the full maturation of the IhNSC-P-derived neurons and their likely functional integration into the host tissue. Thus, IhNSC-Ps possess long-term survival and engraftment capacity upon transplantation into the globally injured ischemic brain, into which they can integrate and mature into neurons, even under mild, transient immunosuppressive conditions. Most notably

  8. Co-transplantation of syngeneic mesenchymal stem cells improves survival of allogeneic glial-restricted precursors in mouse brain.

    Science.gov (United States)

    Srivastava, Amit K; Bulte, Camille A; Shats, Irina; Walczak, Piotr; Bulte, Jeff W M

    2016-01-01

    Loss of functional cells from immunorejection during the early post-transplantation period is an important factor that reduces the efficacy of stem cell-based therapies. Recent studies have shown that transplanted mesenchymal stem cells (MSCs) can exert therapeutic effects by secreting anti-inflammatory and pro-survival trophic factors. We investigated whether co-transplantation of MSCs could improve the survival of other transplanted therapeutic cells. Allogeneic glial-restricted precursors (GRPs) were isolated from the brain of a firefly luciferase transgenic FVB mouse (at E13.5 stage) and intracerebrally transplanted, either alone, or together with syngeneic MSCs in immunocompetent BALB/c mice (n=20) or immunodeficient Rag2(-/-) mice as survival control (n=8). No immunosuppressive drug was given to any animal. Using bioluminescence imaging (BLI) as a non-invasive readout of cell survival, we found that co-transplantation of MSCs significantly improved (ptransplanted cells surviving in both the GRP only and the GRP+MSC group. In contrast, on day 21 post-transplantation, we observed a 94.2% decrease in BLI signal intensity in immunocompetent mice transplanted with GRPs alone versus 68.1% in immunocompetent mice co-transplanted with MSCs and GRPs (pcells, reduced astrogliosis, and a higher number of FoxP3(+) cells at the site of transplantation for the immunocompetent mice receiving MSCs. The present study demonstrates that co-transplantation of MSCs can be used to create a microenvironment that is more conducive to the survival of allogeneic GRPs. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury.

    Science.gov (United States)

    Haus, Daniel L; López-Velázquez, Luci; Gold, Eric M; Cunningham, Kelly M; Perez, Harvey; Anderson, Aileen J; Cummings, Brian J

    2016-07-01

    Traumatic brain injury (TBI) in humans can result in permanent tissue damage and has been linked to cognitive impairment that lasts years beyond the initial insult. Clinically effective treatment strategies have yet to be developed. Transplantation of human neural stem cells (hNSCs) has the potential to restore cognition lost due to injury, however, the vast majority of rodent TBI/hNSC studies to date have evaluated cognition only at early time points, typically cell transplantation. Additionally, human cell engraftment and long-term survival in rodent models of TBI has been difficult to achieve due to host immunorejection of the transplanted human cells, which confounds conclusions pertaining to transplant-mediated behavioral improvement. To overcome these shortfalls, we have developed a novel TBI xenotransplantation model that utilizes immunodeficient athymic nude (ATN) rats as the host recipient for the post-TBI transplantation of human embryonic stem cell (hESC) derived NSCs and have evaluated cognition in these animals at long-term (≥2months) time points post-injury. We report that immunodeficient ATN rats demonstrate hippocampal-dependent spatial memory deficits (Novel Place, Morris Water Maze), but not non-spatial (Novel Object) or emotional/anxiety-related (Elevated Plus Maze, Conditioned Taste Aversion) deficits, at 2-3months post-TBI, confirming that ATN rats recapitulate some of the cognitive deficits found in immunosufficient animal strains. Approximately 9-25% of transplanted hNSCs survived for at least 5months post-transplantation and differentiated into mature neurons (NeuN, 18-38%), astrocytes (GFAP, 13-16%), and oligodendrocytes (Olig2, 11-13%). Furthermore, while this model of TBI (cortical impact) targets primarily cortex and the underlying hippocampus and generates a large lesion cavity, hNSC transplantation facilitated cognitive recovery without affecting either lesion volume or total spared cortical or hippocampal tissue volume. Instead, we

  10. Brain MRI findings of neuropsychiatric lupus

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jang-Wook; Kwon, Bae Ju; Lee, Seung-Ro; Hahm, Chang-Kok; Moon, Won Jin; Jeon, Eui Yong; Bae, Sang-Chul [Hanyang Univ. School of Medicine, Seoul (Korea, Republic of)

    2000-12-01

    To evaluate the brain MRI findings in patients with neuropsychiatric lupus. In 26 patients (M:F = 2:24 ; aged 9-48 years) in whom the presence of systemic lupus erythematosus was clinically or pathologically proven and in whom neuropsychiatric lupus was also clinically diagnosed, the findings of brain MRI were retrospectively evaluated. MR images were analyzed with regard to the distribution, location, size and number of lesions due to cerebral ischemia or infarction, the presence of cerebral atrophy, and the extent and degree of brain parenchymal and intravascular enhancement. The most common MRI findings were lesions due to cerebral ischemia or infarction occurring in 18 patients (69%), and located within deep periventricular white matter (n=10), subcortical white matter (n=8), the cerebral cortex (n=7), basal ganglia (n=7), or brain stem or cerebellum (n=2). The lesions were single (n=3) or multiple (n=15), and in 17 patients were less than 1cm in diameter in regions other than the cerebral cortex. In six of these patients, lesions of 1-4cm in diameter in this region were combined, and one occurred in the cerebral cortex only. Cerebral atrophy was seen in 16 patients (62%), in ten of whom there was no past history of treatment with steroids for more than six months. In 15 patients (58%), contrast-enhanced MR image revealed diffuse enhancement of the basal ganglia or intravascular enhancement. In no case were MRI findings normal. The primary mainfestations of neuropsychiatric lupus are multifocal ischemia or infarctions in the cerebral cortex, and subcortical and deep white matter, and the cerebral atrophy. Contrast-enhanced MR images also demonstrated diffuse enhancement of the basal ganglia and intravascular enhancement, both thought to be related to the congestion due to the stagnation of cerebral blood flow.

  11. Frontal Cortical Atrophy as a Predictor of Poststroke Apathy.

    Science.gov (United States)

    Mihalov, Ján; Mikula, Peter; Budiš, Jaroslav; Valkovič, Peter

    2016-07-01

    The aim of the study was to identify associations between the symptoms of poststroke apathy and sociodemographic, stroke-related (severity of stroke, degree of disability, and performance in activities of daily living), and radiological correlates. We determined the degree of cortical and subcortical brain atrophy, the severity of white matter and basal ganglia lesions on baseline computed tomography (CT) scans, and the localization of acute ischemia on control CT or magnetic resonance imaging scans in subacute stages of stroke. During follow-up examinations, in addition to the assessment of apathy symptoms using the Apathy Scale, we also evaluated symptoms of depression and anxiety using the Hospital Anxiety and Depression Scale. The study included 47 consecutive patients with acute ischemic stroke. Correlates significantly associated with apathy, determined at baseline and during follow-up, were entered into the "predictive" and "associative" multiple regression models, respectively. Frontal cortical atrophy and symptoms of depression were most strongly associated with poststroke apathy symptoms. In order to model an interrelation between both cortical atrophy and white matter lesions and aging, we supplemented 2 additional "predictive" models using interaction variables, whereby we confirmed the role of frontal cortical atrophy as a predictor of poststroke apathy also as a function of the increasing age of patients. © The Author(s) 2016.

  12. Ataxia-telangiectasia: the pattern of cerebellar atrophy on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Tavani, F. [Department of Radiology, University of Modena (Italy); Zimmerman, R.A.; Gatti, R.; Bingham, P. [Department of Radiology, Children' s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, PA 19104, Philadelphia (United States); Berry, G.T. [Department of Endocrinology, Children' s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, PA 19104, Philadelphia (United States); Sullivan, K. [Department of Immunology, Children' s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, PA 19104, Philadelphia (United States)

    2003-05-01

    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.)

  13. Docosahexaenoic acid (DHA) enhances the therapeutic potential of neonatal neural stem cell transplantation post-Traumatic brain injury.

    Science.gov (United States)

    Ghazale, Hussein; Ramadan, Naify; Mantash, Sara; Zibara, Kazem; El-Sitt, Sally; Darwish, Hala; Chamaa, Farah; Boustany, Rose Mary; Mondello, Stefania; Abou-Kheir, Wassim; Soueid, Jihane; Kobeissy, Firas

    2018-03-15

    Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide with 1.5 million people inflicted yearly. Several neurotherapeutic interventions have been proposed including drug administration as well as cellular therapy involving neural stem cells (NSCs). Among the proposed drugs is docosahexaenoic acid (DHA), a polyunsaturated fatty acid, exhibiting neuroprotective properties. In this study, we utilized an innovative intervention of neonatal NSCs transplantation in combination with DHA injections in order to ameliorate brain damage and promote functional recovery in an experimental model of TBI. Thus, NSCs derived from the subventricular zone of neonatal pups were cultured into neurospheres and transplanted in the cortex of an experimentally controlled cortical impact mouse model of TBI. The effect of NSC transplantation was assessed alone and/or in combination with DHA administration. Motor deficits were evaluated using pole climbing and rotarod tests. Using immunohistochemistry, the effect of transplanted NSCs and DHA treatment was used to assess astrocytic (Glial fibrillary acidic protein, GFAP) and microglial (ionized calcium binding adaptor molecule-1, IBA-1) activity. In addition, we quantified neuroblasts (doublecortin; DCX) and dopaminergic neurons (tyrosine hydroxylase; TH) expression levels. Combined NSC transplantation and DHA injections significantly attenuated TBI-induced motor function deficits (pole climbing test), promoted neurogenesis, coupled with an increase in glial reactivity at the cortical site of injury. In addition, the number of tyrosine hydroxylase positive neurons was found to increase markedly in the ventral tegmental area and substantia nigra in the combination therapy group. Immunoblotting analysis indicated that DHA+NSCs treated animals showed decreased levels of 38kDa GFAP-BDP (breakdown product) and 145kDa αII-spectrin SBDP indicative of attenuated calpain/caspase activation. These data demonstrate that prior

  14. Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

    Energy Technology Data Exchange (ETDEWEB)

    Yousry, Indra; Yousry, Tarek A. [Department of Neuroradiology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377, Munich (Germany); Muacevic, Alexander; Olteanu-Nerbe, Vlad [Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich (Germany); Naidich, Thomas P. [Department of Radiology, Section of Neuroradiology, Mount Sinai Hospital, New York (United States)

    2004-07-01

    We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management. (orig.)

  15. Multicystic encephalomalacia associated with symmetrical necrotizing brain stem lesions in an infant: a case report.

    Science.gov (United States)

    Simonati, A; Laverda, A M; Rizzuto, N

    1986-01-01

    The simultaneous occurrence of multicystic encephalomalacia of the cerebral hemispheres, and symmetric necrotizing lesions of diencephalic and infratentorial structures is described in a 15 month-old infant. The baby developed clonic jerks of four limbs a few hours after delivery. She attained no developmental milestones, and remained bed-ridden with hypertonic posture until her death. Multicystic cavities of the cerebral hemispheres were well evident at CT scan when she was 7 months old. The topographic distributions of the different pathological pictures are described; their relationship to the regional properties of the developing brain are commented upon. Etiological aspects of this case are discussed according to present knowledge of the pathophysiological mechanisms leading either to multiple cyst formation or to necrotizing lesions.

  16. Clinical features and autonomic testing predict survival in multiple system atrophy.

    Science.gov (United States)

    Coon, Elizabeth A; Sletten, David M; Suarez, Mariana D; Mandrekar, Jay N; Ahlskog, J Eric; Bower, James H; Matsumoto, Joseph Y; Silber, Michael H; Benarroch, Eduardo E; Fealey, Robert D; Sandroni, Paola; Low, Phillip A; Singer, Wolfgang

    2015-12-01

    Multiple system atrophy is characterized by autonomic failure along with motor symptoms of parkinsonism and/or cerebellar ataxia. There are differing reports on the influence of certain clinical features, including motor subtype (multiple system atrophy-parkinsonism versus multiple system atrophy-cerebellar ataxia), age of onset, gender, and early autonomic symptoms, on the survival in patients with multiple system atrophy. We sought to evaluate overall survival and predictors of survival in a large cohort of patients with multiple system atrophy seen at a single referral centre where objective autonomic testing is routinely performed for this indication. All cases of multiple system atrophy evaluated at Mayo Clinic, Rochester and assessed with an autonomic reflex screen between January 1998 and December 2012 were retrospectively reviewed. A total of 685 patients were identified; 594 met criteria for probable multiple system atrophy, and 91 for possible multiple system atrophy. Multiple system atrophy-parkinsonism was the predominant subtype in 430 patients (63%). Average age of onset was earlier in multiple system atrophy-cerebellar ataxia (58.4 years) compared to multiple system atrophy-parkinsonism (62.3 years; P system atrophy (P = 0.232). An initial motor symptom was most common (61%) followed by autonomic onset (28%) and combined motor and autonomic symptoms (11%). The initial onset of either motor or autonomic symptoms did not influence length of survival. However, a number of clinical and autonomic laboratory features predicted unfavourable survival in a univariate analysis. A multivariate model retained the following unfavourable predictors of survival: (i) falls within 3 years of onset (hazard ratio 2.31, P features can be used to predict survival in patients with multiple system atrophy. Autonomic testing adds an additional, independent predictor of survival, demonstrating its value not only in the diagnosis of multiple system atrophy but also as

  17. Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain

    Directory of Open Access Journals (Sweden)

    Anna-Lena Hallmann

    2016-05-01

    Full Text Available Reprogramming technology enables the production of neural progenitor cells (NPCs from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed transcriptome analyses on murine iNSCs in comparison to brain-derived neural stem cells (NSCs and pluripotent stem cell-derived NPCs, which revealed distinct global, neural, metabolic and cell cycle-associated marks in these populations. iNSCs carried a hindbrain/posterior cell identity, which could be shifted towards caudal, partially to rostral but not towards ventral fates in vitro. iNSCs survived after transplantation into the rodent brain and exhibited in vivo-characteristics, neural and metabolic programs similar to transplanted NSCs. However, iNSCs vastly retained caudal identities demonstrating cell-autonomy of regional programs in vivo. These data could have significant implications for a variety of in vitro- and in vivo-applications using iNSCs.

  18. Over-expression of brain-derived neurotrophic factor in mesenchymal stem cells transfected with recombinant lentivirus BDNF gene.

    Science.gov (United States)

    Zhang, X; Zhu, J; Zhang, K; Liu, T; Zhang, Z

    2016-12-30

    This study was aimed at investigating the expression of brain-derived neurotrophic factor (BDNF) in mesenchymal stem cells (MSCs) modified with recombinant lentivirus bearing BDNF gene. Lentivirus vectors bearing BDNF gene were constructed. MSCs were isolated from rats and cultured. The lentiviral vectors containing BDNF gene were transfected into the MSCs, and BDNF gene and protein expressions were monitored with enhanced green fluorescent protein (EGFP). RT-PCR and Western blot were used to measure gene and protein expressions, respectibvely in MSCs, MSCs-EGFP and MSCs-EGFP-BDNF groups. Green fluorescence assay confirmed successful transfection of BDNF gene recombinant lentivirus into MSCs. RT-PCR and Western blot revealed that BDNF gene and protein expressions in the MSCs-EGFP-BDNF group were significantly higher than that in MSCs group and MSCs-EGFP group. There were no statistically significant differences in gene expression between MSCs and MSCs-EGFP groups. MSCs can over-express BDNF when transfected with recombinant lentivirus bearing BDNF gene.

  19. [A case of primary brain-stem injury recovered from persistent vegetative state after L-dopa administration].

    Science.gov (United States)

    Matsuda, W; Sugimoto, K; Sato, N; Watanabe, T; Yanaka, K; Matsumura, A; Nose, T

    1999-12-01

    A 51-year-old male was transferred to our hospital just after traffic accident. On admission, the patient was comatose (Glasgow Coma Scale of 6) and showed a left hemiparesis with a left oculomotor nerve palsy. Computed tomography demonstrated a traumatic subarachnoid hemorrhage without mass lesion. Magnetic resonance imaging showed high intensity lesions on the left dorsolateral midbrain and the right cerebral peduncle. The distribution of lesions implied diffuse axonal injury involving dopaminergic systems such as the substantia nigra and the ventral tegmental area. After several months of conservative management, the patient showed no recovery and was diagnosed as persistent vegetable state. The administration of L-dopa was then started and the patient showed remarkable neurological improvement. Therefore the patient's neurological status was thought to be modified with primary brain stem injury and accompanying traumatic Parkinson's syndrome. It is important to understand "pseudo" persistent vegetative state in the management of patients showing prolonged consciousness disturbance. L-dopa should be considered as the drugs of pharmacological intervention for the patients of masked parkinsonism behind "pseudo" persistent vegetative state whose dopaminergic systems might have been damaged.

  20. Effect of middle ear effusion on the brain-stem auditory evoked response of Cavalier King Charles Spaniels.

    Science.gov (United States)

    Harcourt-Brown, Thomas R; Parker, John E; Granger, Nicolas; Jeffery, Nick D

    2011-06-01

    Brain-stem auditory evoked responses (BAER) were assessed in 23 Cavalier King Charles Spaniels with and without middle ear effusion at sound intensities ranging from 10 to 100 dB nHL. Significant differences were found between the median BAER threshold for ears where effusions were present (60 dB nHL), compared to those without (30 dB nHL) (P=0.001). The slopes of latency-intensity functions from both groups did not differ, but the y-axis intercept when the x value was zero was greater in dogs with effusions (P=0.009), consistent with conductive hearing loss. Analysis of latency-intensity functions suggested the degree of hearing loss due to middle ear effusion was 21 dB (95% confidence between 10 and 33 dB). Waves I-V inter-wave latency at 90 dB nHL was not significantly different between the two groups. These findings demonstrate that middle ear effusion is associated with a conductive hearing loss of 10-33 dB in affected dogs despite the fact that all animals studied were considered to have normal hearing by their owners. Copyright © 2010. Published by Elsevier Ltd.

  1. The Neuroprotective Effects of Muscle-Derived Stem Cells via Brain-Derived Neurotrophic Factor in Spinal Cord Injury Model

    Directory of Open Access Journals (Sweden)

    Donghe Han

    2017-01-01

    Full Text Available Muscle-derived stem cells (MDSCs possess multipotent differentiation and self-renewal capacities; however, the effects and mechanism in neuron injury remain unclear. The aim of this study was to investigate the effects of MDSCs on neuron secondary injury, oxidative stress-induced apoptosis. An in vivo study showed the Basso, Beattie, and Bresnahan (BBB score and number of neurons significantly increased after MDSCs’ transplantation in spinal cord injury (SCI rats. An in vitro study demonstrated that MDSCs attenuated neuron apoptosis, and the expression of antioxidants was upregulated as well as the ratio of Bcl-2 and Bax in the MNT (MDSCs cocultured with injured neurons group compared with the NT (injured neurons group. Both LC3II/LC3I and β-catenin were enhanced in the MNT group, while XAV939 (a β-catenin inhibitor decreased the expression of nuclear erythroid-related factor 2 (Nrf2 and LC3II/LC3I. Moreover, MDSCs became NSE- (neuron-specific enolase- positive neuron-like cells with brain-derived neurotrophic factor (BDNF treatment. The correlation analysis indicated that there was a significant relation between the level of BDNF and neuron injury. These findings suggest that MDSCs may protect the spinal cord from injury by inhibiting apoptosis and replacing injured neurons, and the increased BDNF and β-catenin could contribute to MDSCs’ effects.

  2. Neuronal coupling by endogenous electric fields: cable theory and applications to coincidence detector neurons in the auditory brain stem.

    Science.gov (United States)

    Goldwyn, Joshua H; Rinzel, John

    2016-04-01

    The ongoing activity of neurons generates a spatially and time-varying field of extracellular voltage (Ve). This Ve field reflects population-level neural activity, but does it modulate neural dynamics and the function of neural circuits? We provide a cable theory framework to study how a bundle of model neurons generates Ve and how this Ve feeds back and influences membrane potential (Vm). We find that these "ephaptic interactions" are small but not negligible. The model neural population can generate Ve with millivolt-scale amplitude, and this Ve perturbs the Vm of "nearby" cables and effectively increases their electrotonic length. After using passive cable theory to systematically study ephaptic coupling, we explore a test case: the medial superior olive (MSO) in the auditory brain stem. The MSO is a possible locus of ephaptic interactions: sounds evoke large (millivolt scale)Vein vivo in this nucleus. The Ve response is thought to be generated by MSO neurons that perform a known neuronal computation with submillisecond temporal precision (coincidence detection to encode sound source location). Using a biophysically based model of MSO neurons, we find millivolt-scale ephaptic interactions consistent with the passive cable theory results. These subtle membrane potential perturbations induce changes in spike initiation threshold, spike time synchrony, and time difference sensitivity. These results suggest that ephaptic coupling may influence MSO function. Copyright © 2016 the American Physiological Society.

  3. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    Science.gov (United States)

    Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

    2014-01-01

    Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal

  4. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    Directory of Open Access Journals (Sweden)

    Haejin Lee

    Full Text Available Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%, APC-CC1+ oligodendrocytes (∼28%, and GFAP+ astrocytes (∼8%. Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest

  5. Neuronal involvement in muscular atrophy

    Directory of Open Access Journals (Sweden)

    Bruno Alejandro Cisterna

    2014-12-01

    Full Text Available The innervation of skeletal myofibers exerts a crucial influence on the maintenance of muscle tone and normal operation. Consequently, denervated myofibers manifest atrophy, which is preceded by an increase in sarcolemma permeability. Recently, de novo expression of hemichannels formed by connexins and other none selective channels, including P2X7 receptors, TRPV2 channels were demonstrated in denervated fast skeletal muscles. The denervation-induced atrophy was drastically prevented in denervated muscles deficient in connexins 43 and 45. Nonetheless, the transduction mechanism by which the nerve represses the expression of the above mentioned none selective channels remains unknown. The paracrine action of extracellular signaling molecules including ATP, neurotrophic factors (i.e., BDNF, agrin/Lrp4/MuSK and acetylcholine are among the possible perpetrators of repression for connexin expression. This review discusses the possible role of relevant factors in maintaining the normal functioning of fast skeletal muscles and suppression of connexin hemichannel expression.

  6. Poor sleep quality is associated with increased cortical atrophy in community-dwelling adults.

    Science.gov (United States)

    Sexton, Claire E; Storsve, Andreas B; Walhovd, Kristine B; Johansen-Berg, Heidi; Fjell, Anders M

    2014-09-09

    To examine the relationship between sleep quality and cortical and hippocampal volume and atrophy within a community-based sample, explore the influence of age on results, and assess the possible confounding effects of physical activity levels, body mass index (BMI), and blood pressure. In 147 community-dwelling adults (92 female; age 53.9 ± 15.5 years), sleep quality was measured using the Pittsburgh Sleep Quality Index and correlated with cross-sectional measures of volume and longitudinal measures of atrophy derived from MRI scans separated by an average of 3.5 years. Exploratory post hoc analysis compared correlations between different age groups and included physical activity, BMI, and blood pressure as additional covariates. Poor sleep quality was associated with reduced volume within the right superior frontal cortex in cross-sectional analyses, and an increased rate of atrophy within widespread frontal, temporal, and parietal regions in longitudinal analyses. Results were largely driven by correlations within adults over the age of 60, and could not be explained by variation in physical activity, BMI, or blood pressure. Sleep quality was not associated with hippocampal volume or atrophy. We found that longitudinal measures of cortical atrophy were widely correlated with sleep quality. Poor sleep quality may be a cause or a consequence of brain atrophy, and future studies examining the effect of interventions that improve sleep quality on rates of atrophy may hold key insights into the direction of this relationship. © 2014 American Academy of Neurology.

  7. Neocortical Neuronal Loss in Patients with Multiple System Atrophy

    DEFF Research Database (Denmark)

    Salvesen, Lisette; Winge, Kristian; Brudek, Tomasz

    2017-01-01

    with MSA and 11 age- and gender-matched control subjects. The stereological data were supported by cell marker expression analyses in tissue samples from the prefrontal cortex. We found significantly fewer neurons in the frontal and parietal cortex of MSA brains compared with control brains. Significantly......To determine the extent of neocortical involvement in multiple system atrophy (MSA), we used design-based stereological methods to estimate the total numbers of neurons, oligodendrocytes, astrocytes, and microglia in the frontal, parietal, temporal, and occipital cortex of brains from 11 patients...... more astrocytes and microglia were observed in the frontal, parietal, and temporal cortex of MSA brains, whereas no change in the total number of oligodendrocytes was seen in any of the neocortical regions. There were significantly fewer neurons in the frontal cortex of MSA patients with impaired...

  8. Robust Identification of Alzheimer’s Disease subtypes based on cortical atrophy patterns

    Science.gov (United States)

    Park, Jong-Yun; Na, Han Kyu; Kim, Sungsoo; Kim, Hyunwook; Kim, Hee Jin; Seo, Sang Won; Na, Duk L.; Han, Cheol E.; Seong, Joon-Kyung; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Liu, Enchi; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; Decarli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven G.; Shen, Li; Kelley, Faber; Kim, Sungeun; Nho, Kwangsik; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Doody, Rachelle S.; Villanueva Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; de Toledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; D'Agostino, Daniel, II; Kielb, Stephanie; Galvin, James E.; Pogorelec, Dana M.; Cerbone, Brittany; Michel, Christina A.; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; de Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Wong, Terence Z.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L.; Oakley, Maryann; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc Adams Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz Arrastia, Ramon; King, Richard; Weiner, Myron; Martin Cook, Kristen; Devous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H. S.; Lu, Po H.; Bartzokis, George; Graff Radford, Neill R.; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Farlow, Martin R.; Marie Hake, Ann; Matthews, Brandy R.; Herring, Scott; Hunt, Cynthia; van Dyck, Christopher H.; Carson, Richard E.; Macavoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging Yuek; Feldman, Howard; Mudge, Benita; Assaly, Michele; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Marsel Mesulam, Marek; Lipowski, Kristine; Kuo Wu, Chuang; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Lynn Johnson, Patricia; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Hudson, Leon; Fletcher, Evan; Carmichael, Owen; Olichney, John; Kittur, Smita; Borrie, Michael; Lee, T. Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Santulli, Robert B.; Kitzmiller, Tamar J.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Finger, Elizabether; Pasternak, Stephen; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Smith, Karen Elizabeth; Relkin, Norman; Chaing, Gloria; Raudin, Lisa; Smith, Amanda; Fargher, Kristin; Raj, Balebail Ashok

    2017-03-01

    Accumulating evidence suggests that Alzheimer’s disease (AD) is heterogenous and can be classified into several subtypes. Here, we propose a robust subtyping method for AD based on cortical atrophy patterns and graph theory. We calculated similarities between subjects in their atrophy patterns throughout the whole brain, and clustered subjects with similar atrophy patterns using the Louvain method for modular organization extraction. We applied our method to AD patients recruited at Samsung Medical Center and externally validated our method by using the AD Neuroimaging Initiative (ADNI) dataset. Our method categorized very mild AD into three clinically distinct subtypes with high reproducibility (>90%) the parietal-predominant (P), medial temporal-predominant (MT), and diffuse (D) atrophy subtype. The P subtype showed the worst clinical presentation throughout the cognitive domains, while the MT and D subtypes exhibited relatively mild presentation. The MT subtype revealed more impaired language and executive function compared to the D subtype.

  9. Intravenous xenotransplantation of human placental mesenchymal stem cells to rats: comparative analysis of homing in rat brain in two models of experimental ischemic stroke.

    Science.gov (United States)

    Kholodenko, I V; Yarygin, K N; Gubsky, L V; Konieva, A A; Tairova, R T; Povarova, O V; Kholodenko, R V; Burunova, V V; Yarygin, V N; Skvortsova, V I

    2012-11-01

    Mesenchymal stem cells from human placenta obtained after term natural delivery were cultured and labeled with vital dye Dil of magnetic fluorescing microparticles. The labeled cells were transplanted intravenously to rats with occlusion of the median cerebral artery. Penetration of cells through the brain-blood barrier and their distribution in the brain of experimental animals were studied on serial cryostat sections. Two models of cerebral artery occlusion associated with different traumatic consequences were used. The efficiency of crossing the blood-brain barrier by transplanted cells, the number of mesenchymal cells attaining the ischemic focus and neurogenic zones, and the time of death of transplanted cells largely depended on the degree and nature of injury to the central nervous system, which should be taken into account when planning the experiments for evaluation of the effects of cell therapy on the models of neurological diseases and in clinical studies in the field of regenerative neurology.

  10. Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia.

    Science.gov (United States)

    Fukawa, Tomoya; Yan-Jiang, Benjamin Chua; Min-Wen, Jason Chua; Jun-Hao, Elwin Tan; Huang, Dan; Qian, Chao-Nan; Ong, Pauline; Li, Zhimei; Chen, Shuwen; Mak, Shi Ya; Lim, Wan Jun; Kanayama, Hiro-Omi; Mohan, Rosmin Elsa; Wang, Ruiqi Rachel; Lai, Jiunn Herng; Chua, Clarinda; Ong, Hock Soo; Tan, Ker-Kan; Ho, Ying Swan; Tan, Iain Beehuat; Teh, Bin Tean; Shyh-Chang, Ng

    2016-06-01

    Cachexia is a devastating muscle-wasting syndrome that occurs in patients who have chronic diseases. It is most commonly observed in individuals with advanced cancer, presenting in 80% of these patients, and it is one of the primary causes of morbidity and mortality associated with cancer. Additionally, although many people with cachexia show hypermetabolism, the causative role of metabolism in muscle atrophy has been unclear. To understand the molecular basis of cachexia-associated muscle atrophy, it is necessary to develop accurate models of the condition. By using transcriptomics and cytokine profiling of human muscle stem cell-based models and human cancer-induced cachexia models in mice, we found that cachectic cancer cells secreted many inflammatory factors that rapidly led to high levels of fatty acid metabolism and to the activation of a p38 stress-response signature in skeletal muscles, before manifestation of cachectic muscle atrophy occurred. Metabolomics profiling revealed that factors secreted by cachectic cancer cells rapidly induce excessive fatty acid oxidation in human myotubes, which leads to oxidative stress, p38 activation and impaired muscle growth. Pharmacological blockade of fatty acid oxidation not only rescued human myotubes, but also improved muscle mass and body weight in cancer cachexia models in vivo. Therefore, fatty acid-induced oxidative stress could be targeted to prevent cancer-induced cachexia.

  11. Bilateral cerebellar and brain stem infarction resulting from vertebral artery injury following cervical trauma without radiographic damage of the spinal column: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Mimata, Yoshikuni; Sato, Kotaro; Suzuki, Yoshiaki [Iwate Prefectural Chubu Hospital, Department of Orthopaedic Surgery, Kitakami (Japan); Murakami, Hideki [Iwate Medical University, Department of Orthopaedic Surgery, School of Medicine, Morioka (Japan)

    2014-01-15

    Vertebral artery injury can be a complication of cervical spine injury. Although most cases are asymptomatic, the rare case progresses to severe neurological impairment and fatal outcomes. We experienced a case of bilateral cerebellar and brain stem infarction with fatal outcome resulting from vertebral artery injury associated with cervical spine trauma. A 69-year-old male was admitted to our hospital because of tetraplegia after falling down the stairs and hitting his head on the floor. Marked bony damage of the cervical spine was not apparent on radiographs and CT scans, so the injury was initially considered to be a cervical cord injury without bony damage. However, an intensity change in the intervertebral disc at C5/C6, and a ventral epidural hematoma were observed on MRI. A CT angiogram of the neck showed the right vertebral artery was completely occluded at the C4 level of the spine. Forty-eight hours after injury, the patient lapsed into drowsy consciousness. The cranial CT scan showed a massive low-density area in the bilateral cerebellar hemispheres and brain stem. Anticoagulation was initiated after a diagnosis of the right vertebral artery injury, but the patient developed bilateral cerebellar and brain stem infarction. The patient's brain herniation progressed and the patient died 52 h after injury. We considered that not only anticoagulation but also treatment for thrombosis would have been needed to prevent cranial embolism. We fully realize that early and appropriate treatment are essential to improve the treatment results, and constructing a medical system with a team of orthopedists, radiologists, and neurosurgeons is also very important. (orig.)

  12. Global Cerebral Atrophy Detected by Routine Imaging: Relationship with Age, Hippocampal Atrophy, and White Matter Hyperintensities.

    Science.gov (United States)

    Al-Janabi, Omar M; Panuganti, Pradeep; Abner, Erin L; Bahrani, Ahmed A; Murphy, Ronan; Bardach, Shoshana H; Caban-Holt, Allison; Nelson, Peter T; Gold, Brian T; Smith, Charles D; Wilcock, Donna M; Jicha, Gregory A

    2018-01-05

    Interpreting the clinical significance of moderate-to-severe global cerebral atrophy (GCA) is a conundrum for many clinicians, who visually interpret brain imaging studies in routine clinical practice. GCA may be attributed to normal aging, Alzheimer's disease (AD), or cerebrovascular disease (CVD). Understanding the relationships of GCA with aging, AD, and CVD is important for accurate diagnosis and treatment decisions for cognitive complaints. To elucidate the relative associations of age, moderate-to-severe white matter hyperintensities (WMHs), and moderate-to-severe medial temporal lobe atrophy (MTA), with moderate-to-severe GCA, we visually rated clinical brain imaging studies of 325 participants from a community based sample. Logistic regression analysis was conducted to assess the relations of GCA with age, WMH, and MTA. The mean age was 76.2 (±9.6) years, 40.6% were male, and the mean educational attainment was 15.1 (±3.7) years. Logistic regression results demonstrated that while a 1-year increase in age was associated with GCA (OR = 1.04; P = .04), MTA (OR = 3.7; P < .001), and WMH (OR = 8.80; P < .001) were strongly associated with GCA in our study population. Partial correlation analysis showed that the variance of GCA explained by age is less than the variance attributed to MTA and WMH (r = .13, .21, and .43, respectively). Moderate-to-severe GCA is most likely to occur in the presence of AD or CVD and should not be solely attributed to age when evaluating clinical imaging findings in the workup of cognitive complaints. Developing optimal diagnostic and treatment strategies for cognitive decline in the setting of GCA requires an understanding of its risk factors in the aging population. Copyright © 2018 by the American Society of Neuroimaging.

  13. The effect of simvastatin treatment on proliferation and differentiation of neural stem cells after traumatic brain injury.

    Science.gov (United States)

    Xie, Chuncheng; Cong, Damin; Wang, Xiujuan; Wang, Yuehua; Liang, Hongsheng; Zhang, Xiangtong; Huang, Qi

    2015-03-30

    To study the effect of simvastatin on neurological functional recovery after traumatic brain injuries (TBI) and the possible molecular mechanisms, we evaluated simvastatin-induced proliferation and differentiation of neural stem cells (NSCs) in vitro and in vivo and possible involvement of Notch-1 signaling in this process. Adult Wistar rats were randomly divided into three groups (n=28 for each): sham group, saline-treated group and simvastatin-treated group. Simvastatin was given orally at a dose of 1mg/kg/day starting at day 1 after TBI. At 1, 3, 7, 14, 21, 28, and 35 days after simvastatin treatment, functional outcome was measured using modified neurological severity scores (mNSS). Immunofluorescence of nestin was used to identify neurogenesis of NSCs in injured area of TBI rats. Western blot was applied to detect the expression level of Notch-1 protein in TBI rats with simvastatin. Immunostaining showed a significant increase in the number of nestin-positive cells in injured area of the simvastatin-treated group compared to that of the saline-treated group (p<0.05). In in vitro experiment, simvastatin induced enhanced proliferation and neurogenesis of cultured NSCs and elevated Notch-1 protein expression. Co-incubation of γ-secretase inhibitor, an inhibitor of Notch-1 pathway, with simvastatin abolished its neurorestoration effect. Most importantly, the simvastatin-treated group had significantly decreased mNSS at day 35 after TBI compared with the saline-treated group (p<0.05). Simvastatin treatment enhanced neurological functional recovery after TBI possibly via activation of Notch signaling and increasing neurogenesis in the injured area. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Slowly progressive anarthria with late anterior opercular syndrome: a variant form of frontal cortical atrophy syndromes.

    Science.gov (United States)

    Broussolle, E; Bakchine, S; Tommasi, M; Laurent, B; Bazin, B; Cinotti, L; Cohen, L; Chazot, G

    1996-12-01

    We describe eight patients with slowly progressive speech production deficit combining speech apraxia, dysarthria, dysprosody and orofacial apraxia, and initially no other deficit in other language and non-language neuropsychological domains. Long-term follow-up (6-10 years) in 4 cases showed an evolution to muteness, bilateral suprabulbar paresis with automatic-voluntary dissociation and frontal lobe cognitive slowing without generalised intellectual deterioration. Most disabled patients presented with an anterior opercular syndrome (Foix-Chavany-Marie syndrome), and pyramidal or extrapyramidal signs. CT and MRI findings disclosed asymmetric (left > right) progressive cortical atrophy of the frontal lobes predominating in the posterior inferior frontal region, notably the operculum. SPECT and PET revealed a decreased cerebral blood flow and metabolism, prominent in the left posterior-inferior frontal gyrus and premotor cortex, extending bilaterally in the most advanced cases. Pathological study of two cases showed non-specific neuronal loss, gliosis, and spongiosis of superficial cortical layers, mainly confined to the frontal lobes, with no significant abnormalities in the basal ganglia, thalamus, cerebellum, brain stem (except severe neuronal loss in the substantia nigra in one case), and spinal cord. We propose to call this peculiar syndrome Slowly Progressive Anarthria (SPA), based on its specific clinical presentation, and its metabolic and pathological correlates. SPA represents another clinical expression of focal cortical degeneration syndromes, that may overlap with other similar syndromes, specially primary progressive aphasia and the various frontal lobe dementias.

  15. Microvillous inclusion disease (microvillous atrophy

    Directory of Open Access Journals (Sweden)

    Goulet Olivier

    2006-06-01

    Full Text Available Abstract Microvillous inclusion disease (MVID or microvillous atrophy is a congenital disorder of the intestinal epithelial cells that presents with persistent life-threatening watery diarrhea and is characterized by morphological enterocyte abnormalities. MVID manifests either in the first days of life (early-onset form or in the first two months (late-onset form of life. MVID is a very rare disorder of unknown origin, probably transmitted as an autosomal recessive trait. To date, no prevalence data are available. Ultrastructural analyses reveal: 1 a partial to total atrophy of microvilli on mature enterocytes with apical accumulation of numerous secretory granules in immature enterocytes; 2 the highly characteristic inclusion bodies containing rudimentary or fully differentiated microvilli in mature enterocytes. Light microscopy shows accumulation of PAS-positive granules at the apical pole of immature enterocytes, together with atrophic band indicating microvillus atrophy and, in parallel, an intracellular PAS or CD10 positive line (marking the microvillous inclusion bodies seen on electron microscopy. Intestinal failure secondary to diarrhea is definitive. To date, no curative therapy exists and children with MVID are totally dependent on parenteral nutrition. Long-term outcome is generally poor, due to metabolic decompensation, repeated states of dehydration, infectious and liver complications related to the parenteral nutrition. As MVID is a very rare disorder, which is extremely difficult to diagnose and manage, children with MVID should be transferred to specialized pediatric gastro-intestinal centers, if possible, a center equipped to perform small bowel transplantation. Early small bowel transplantation resulting in intestinal autonomy gives new hope for disease management and outcome.

  16. Subretinal Glial Membranes in Eyes With Geographic Atrophy.

    Science.gov (United States)

    Edwards, Malia M; McLeod, D Scott; Bhutto, Imran A; Grebe, Rhonda; Duffy, Maeve; Lutty, Gerard A

    2017-03-01

    Müller cells create the external limiting membrane (ELM) by forming junctions with photoreceptor cells. This study evaluated the relationship between focal photoreceptors and RPE loss in geographic atrophy (GA) and Müller cell extension into the subretinal space. Human donor eyes with no retinal disease or geographic atrophy (GA) were fixed and the eye cups imaged. The retinal posterior pole was stained for glial fibrillary acidic protein (GFAP; astrocytes and activated Müller cells) and vimentin (Müller cells) while the submacular choroids were labeled with Ulex Europaeus Agglutinin lectin (blood vessels). Choroids and retinas were imaged using a Zeiss 710 confocal microscope. Additional eyes were cryopreserved or processed for transmission electron microscopy (TEM) to better visualize the Müller cells. Vimentin staining of aged control retinas (n = 4) revealed a panretinal cobblestone-like ELM. While this pattern was also observed in the GA retinas (n = 7), each also had a distinct area in which vimentin+ and vimentin+/GFAP+ processes created a subretinal membrane. Subretinal glial membranes closely matched areas of RPE atrophy in the gross photos. Choroidal vascular loss was also evident in these atrophic areas. Smaller glial projections were noted, which correlated with drusen in gross photos. The presence of glia in the subretinal space was confirmed by TEM and cross cross-section immunohistochemistry. In eyes with GA, subretinal Müller cell membranes present in areas of RPE atrophy may be a Müller cell attempt to replace the ELM. These membranes could interfere with treatments such as stem cell therapy.

  17. Distinct white matter injury associated with medial temporal lobe atrophy in Alzheimer's versus semantic dementia.

    Science.gov (United States)

    Bejanin, Alexandre; Desgranges, Béatrice; La Joie, Renaud; Landeau, Brigitte; Perrotin, Audrey; Mézenge, Florence; Belliard, Serge; de La Sayette, Vincent; Eustache, Francis; Chételat, Gaël

    2017-04-01

    This study aims at further understanding the distinct vulnerability of brain networks in Alzheimer's disease (AD) versus semantic dementia (SD) investigating the white matter injury associated with medial temporal lobe (MTL) atrophy in both conditions. Twenty-six AD patients, twenty-one SD patients, and thirty-nine controls underwent a high-resolution T1-MRI scan allowing to obtain maps of grey matter volume and white matter density. A statistical conjunction approach was used to identify MTL regions showing grey matter atrophy in both patient groups. The relationship between this common grey matter atrophy and white matter density maps was then assessed within each patient group. Patterns of grey matter atrophy were distinct in AD and SD but included a common region in the MTL, encompassing the hippocampus and amygdala. This common atrophy was associated with alterations in different white matter areas in AD versus SD, mainly including the cingulum and corpus callosum in AD, while restricted to the temporal lobe - essentially the uncinate and inferior longitudinal fasciculi - in SD. Complementary analyses revealed that these relationships remained significant when controlling for global atrophy or disease severity. Overall, this study provides the first evidence that atrophy of the same MTL region is related to damage in distinct white matter fibers in AD and SD. These different patterns emphasize the vulnerability of distinct brain networks related to the MTL in these two disorders, which might underlie the discrepancy in their symptoms. These results further suggest differences between AD and SD in the neuropathological processes occurring in the MTL. Hum Brain Mapp 38:1791-1800, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Comparing brain-derived neurotrophic factor and ciliary neurotrophic factor secretion of induced neurotrophic factor secreting cells from human adipose and bone marrow-derived stem cells.

    Science.gov (United States)

    Razavi, Shahnaz; Razavi, Mohamad Reza; Zarkesh Esfahani, Hamid; Kazemi, Mohammad; Mostafavi, Fatemeh Sadat

    2013-08-01

    Adipose derived stem cells (ADSCs) and bone marrow stem cells (BMSCs) may be equally beneficial in treating neurodegenerative diseases. However, ADSCs have practical advantages. In this study, we aimed to induce neurotrophic factors secreting cells in human ADSCs. Then, we compared the level of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion in neurotrophic factors secreting cells from human adipose and bone marrow-derived stem cells. Isolated human ADSCs and BMSCs were induced to neurotrophic factor (NTF)-secreting cells. The levels of expression and secretion of BDNF and CTNF of induced cells were assessed using immunocytochemical, Real-Time polymerase chain reaction, and enzyme linked immunosorbent assay (ELISA). The level of BDNF significantly increased in both the induced mesenchymal stem cells (MSCs) relative to ADSCs and the BMSCs (P < 0.01). Moreover, ELISA analysis showed that the release of BDNF in the induced BMSCs was almost twofold more than the induced ADSCs. Overall, NTF-secreting factor cells derived BMSCs and ADSCs could secret a range of different growth factors. Therefore, the variation in neurotrophic factors of different induced MSC populations suggest the possible beneficial effect of each specific kind of neurotrophic factor secreting cells for the treatment of a particular neurodegenerative disease. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

  19. Can adult neural stem cells create new brains? Plasticity in the adult mammalian neurogenic niches: realities and expectations in the era of regenerative biology.

    Science.gov (United States)

    Kazanis, Ilias

    2012-02-01

    Since the first experimental reports showing the persistence of neurogenic activity in the adult mammalian brain, this field of neurosciences has expanded significantly. It is now widely accepted that neural stem and precursor cells survive during adulthood and are able to respond to various endogenous and exogenous cues by altering their proliferation and differentiation activity. Nevertheless, the pathway to therapeutic applications still seems to be long. This review attempts to summarize and revisit the available data regarding the plasticity potential of adult neural stem cells and of their normal microenvironment, the neurogenic niche. Recent data have demonstrated that adult neural stem cells retain a high level of pluripotency and that adult neurogenic systems can switch the balance between neurogenesis and gliogenesis and can generate a range of cell types with an efficiency that was not initially expected. Moreover, adult neural stem and precursor cells seem to be able to self-regulate their interaction with the microenvironment and even to contribute to its synthesis, altogether revealing a high level of plasticity potential. The next important step will be to elucidate the factors that limit this plasticity in vivo, and such a restrictive role for the microenvironment is discussed in more details.

  20. Comparative study of expression and activity of glucose transporters between stem cell-derived brain microvascular endothelial cells and hCMEC/D3 cells.

    Science.gov (United States)

    Al-Ahmad, Abraham J

    2017-10-01

    Glucose constitutes a major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs). We investigated the expression of different glucose transporters at the BBB using immunocytochemistry and flow cytometry and measured glucose uptake and diffusion across BMEC monolayers obtained from two iPSC lines and from hCMEC/D3 cells. BMEC monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3, and GLUT4. Diffusion of glucose across the monolayers was mediated via a saturable transcellular mechanism and partially inhibited by pharmacological inhibitors. Taken together, our study suggests the presence of several glucose transporters isoforms at the human BBB and demonstrates the feasibility of modeling glucose across the BBB using patient-derived stem cells. Copyright © 2017 the American Physiological Society.

  1. In vitro model of cerebral ischemia by using brain microvascular endothelial cells derived from human induced pluripotent stem cells.

    Science.gov (United States)

    Kokubu, Yasuhiro; Yamaguchi, Tomoko; Kawabata, Kenji

    2017-04-29

    Brain-derived microvascular endothelial cells (BMECs), which play a central role in blood brain barrier (BBB), can be used for the evaluation of drug transport into the brain. Although human BMEC cell lines have already been reported, they lack original properties such as barrier integrity. Pluripotent stem cells (PSCs) can be used for various applications such as regenerative therapy, drug screening, and pathological study. In the recent study, an induction method of BMECs from PSCs has been established, making it possible to more precisely study the in vitro human BBB function. Here, using induced pluripotent stem (iPS) cell-derived BMECs, we examined the effects of oxygen-glucose deprivation (OGD) and OGD/reoxygenation (OGD/R) on BBB permeability. OGD disrupted the barrier function, and the dysfunction was rapidly restored by re-supply of the oxygen and glucose. Interestingly, TNF-α, which is known to be secreted from astrocytes and microglia in the cerebral ischemia, prevented the restoration of OGD-induced barrier dysfunction in an apoptosis-independent manner. Thus, we could establish the in vitro BBB disease model that mimics the cerebral ischemia by using iPS cell-derived BMECs. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. High-dose Chemotherapy With Autologous Stem Cell Rescue in Saudi Children Less Than 3 Years of Age With Embryonal Brain Tumors.

    Science.gov (United States)

    Alsultan, Abdulrahman; Alharbi, Musa; Al-Dandan, Sadeq; Bayoumi, Yasser; Alharbi, Talal; Alsudairy, Reem; Alomari, Ali; Aljamaan, Khalid; Musleh, Othman; Alharbi, Qasim; Jarrar, Mohammed

    2015-04-01

    High-dose chemotherapy with autologous stem cell rescue (HDC/ASCR) has been used in children under the age of 3 years with embryonal brain tumors to avoid or delay the use of radiation. We reviewed the medical records of 10 Saudi children less than 3 years of age with embryonal brain tumors who underwent HDC/ASCR. All 10 patients underwent surgical resection followed by 3 to 5 cycles of induction chemotherapy and 1 to 3 cycles of HDC/ASCR using carboplatin and thiotepa. Isotretinoin was used as a maintenance therapy in 4 patients. Five patients had medulloblastoma, 3 had atypical teratoid/rhabdoid tumors, 1 had an embryonal tumor with abundant neuropil and true rosettes, and 1 had pineoblastoma. The median age of the patients was 1.9 years. A total of 19 HDC/ASCR procedures were performed. Radiotherapy (RT) was administered to 5 patients after HDC/ASCR and as a salvage therapy in 1 patient. The progression-free survival rate was 50% at 1 year and at 2 years, with a median follow-up of 24 months. All 5 patients with medulloblastoma are still alive without evidence of disease, but the other patients died secondary to tumor progression. This experience suggests that strategies combining myeloablative chemotherapy and autologous stem cell rescue appear to be feasible for children with embryonal brain tumors in the Middle East.

  3. Spinal cord atrophy in anterior-posterior direction reflects impairment in multiple sclerosis

    DEFF Research Database (Denmark)

    Lundell, H; Svolgaard, O; Dogonowski, A-M

    2017-01-01

    OBJECTIVE: To investigate how atrophy is distributed over the cross section of the upper cervical spinal cord and how this relates to functional impairment in multiple sclerosis (MS). METHODS: We analysed the structural brain MRI scans of 54 patients with relapsing-remitting MS (n=22), primary...... and specific MSIS subscores. CONCLUSION: In patients with MS, atrophy of the upper cervical cord is most evident in the antero-posterior direction. As APW of the cervical cord can be readily derived from standard structural MRI of the brain, APW constitutes a clinically useful neuroimaging marker of disease...... these atrophy measures and clinical impairments as reflected by the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impairment Scale (MSIS). RESULTS: In patients with MS, CSA and APW but not LRW were reduced compared to healthy controls (P

  4. [Posterior cortical atrophy with incomplete Bálint's syndrome].

    Science.gov (United States)

    Iizuka, O; Soma, Y; Otsuki, M; Endo, K; Tanno, Y; Tsuji, S

    1997-09-01

    We report a patient of posterior cortical atrophy (PCA) with progressive memory disturbance and incomplete Bálint's syndrome consisting of optic ataxie (ataxie optique type) and visual inattention without psychic paralysis of fixation of gaze. The patients is a 58-year-old woman who noticed memory disturbance at 53 years old. Neurological deficit at 54 years old was detected only in the domain of memory, and mild diffuse brain atrophy was revealed on MRI. Memory disturbance progressed gradually, and at the age of 58 she was noticed to have visual disorder. Neuropsychological examination revealed severe memory disorder, incomplete Bálint's syndrome, transcortical sensory aphasia, mild ideational apraxia, and severe constructional apraxia. Visual inattention was too severe to evaluate visual acuity and visual field. MRI showed moderate dilatation of bilateral lateral ventricles, especially in their posterior horns, with atrophy of bilateral temporo-parieto-occipital lobes and hippocampus. IMP-SPECT revealed a diffuse decrease of cerebral blood flow in the bilateral temporo-parieto-occipital region, predominantly in the parietal regions. We believe that she is still in the early phase of PCA, and that psychic paralysis of fixation of gaze, visual agnosia will be noted in several years. Our patient represents an example of early stage PCA from neuropsychological and MRI findings.

  5. Religious factors and hippocampal atrophy in late life.

    Directory of Open Access Journals (Sweden)

    Amy D Owen

    2011-03-01

    Full Text Available Despite a growing interest in the ways spiritual beliefs and practices are reflected in brain activity, there have been relatively few studies using neuroimaging data to assess potential relationships between religious factors and structural neuroanatomy. This study examined prospective relationships between religious factors and hippocampal volume change using high-resolution MRI data of a sample of 268 older adults. Religious factors assessed included life-changing religious experiences, spiritual practices, and religious group membership. Hippocampal volumes were analyzed using the GRID program, which is based on a manual point-counting method and allows for semi-automated determination of region of interest volumes. Significantly greater hippocampal atrophy was observed for participants reporting a life-changing religious experience. Significantly greater hippocampal atrophy was also observed from baseline to final assessment among born-again Protestants, Catholics, and those with no religious affiliation, compared with Protestants not identifying as born-again. These associations were not explained by psychosocial or demographic factors, or baseline cerebral volume. Hippocampal volume has been linked to clinical outcomes, such as depression, dementia, and Alzheimer's Disease. The findings of this study indicate that hippocampal atrophy in late life may be uniquely influenced by certain types of religious factors.

  6. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial.

    Science.gov (United States)

    Gondi, Vinai; Pugh, Stephanie L; Tome, Wolfgang A; Caine, Chip; Corn, Ben; Kanner, Andrew; Rowley, Howard; Kundapur, Vijayananda; DeNittis, Albert; Greenspoon, Jeffrey N; Konski, Andre A; Bauman, Glenn S; Shah, Sunjay; Shi, Wenyin; Wendland, Merideth; Kachnic, Lisa; Mehta, Minesh P

    2014-12-01

    Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05. Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, -4.7% to 18.7%), significantly lower in comparison with the historical control (P memory and QOL as compared with historical series. © 2014 by American Society of Clinical Oncology.

  7. 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

  8. Isolation of Neural Stem and Progenitor Cells from the Adult Brain and Live Imaging of Their Cell Cycle with the FUCCI System.

    Science.gov (United States)

    Chicheportiche, Alexandra; Ruat, Martial; Boussin, François D; Daynac, Mathieu

    2018-01-01

    Neural stem cells (NSCs) enter quiescence in early embryonic stages to create a reservoir of dormant NSCs able to enter proliferation and produce neuronal precursors in the adult mammalian brain. Various approaches of fluorescent-activated cell sorting (FACS) have emerged to allow the distinction between quiescent NSCs (qNSCs), their activated counterpart (aNSCs), and the resulting progeny. In this article, we review two FACS techniques that can be used alternatively. We also show that their association with transgenic Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) mice allows an unprecedented overlook on the cell cycle dynamics of adult NSCs.

  9. Evolution of Cerebral Atrophy in a Patient with Super Refractory Status Epilepticus Treated with Barbiturate Coma

    Directory of Open Access Journals (Sweden)

    Christopher R. Newey

    2017-01-01

    Full Text Available Introduction. Status epilepticus is associated with neuronal breakdown. Radiological sequelae of status epilepticus include diffusion weighted abnormalities and T2/FLAIR cortical hyperintensities corresponding to the epileptogenic cortex. However, progressive generalized cerebral atrophy from status epilepticus is underrecognized and may be related to neuronal death. We present here a case of diffuse cerebral atrophy that developed during the course of super refractory status epilepticus management despite prolonged barbiturate coma. Methods. Case report and review of the literature. Case. A 19-year-old male with a prior history of epilepsy presented with focal clonic seizures. His seizures were refractory to multiple anticonvulsants and eventually required pentobarbital coma for 62 days and midazolam coma for 33 days. Serial brain magnetic resonance imaging (MRI showed development of cerebral atrophy at 31 days after admission to our facility and progression of the atrophy at 136 days after admission. Conclusion. This case highlights the development and progression of generalized cerebral atrophy in super refractory status epilepticus. The cerebral atrophy was noticeable at 31 days after admission at our facility which emphasizes the urgency of definitive treatment in patients who present with super refractory status epilepticus. Further research into direct effects of therapeutic coma is warranted.

  10. Carrier testing for spinal muscular atrophy

    Science.gov (United States)

    Gitlin, Jonathan M.; Fischbeck, Kenneth; Crawford, Thomas O.; Cwik, Valerie; Fleischman, Alan; Gonye, Karla; Heine, Deborah; Hobby, Kenneth; Kaufmann, Petra; Keiles, Steven; MacKenzie, Alex; Musci, Thomas; Prior, Thomas; Lloyd-Puryear, Michele; Sugarman, Elaine A.; Terry, Sharon F.; Urv, Tiina; Wang, Ching; Watson, Michael; Yaron, Yuval; Frosst, Phyllis; Howell, R. Rodney

    2014-01-01

    Spinal muscular atrophy is the most common fatal hereditary disease among newborns and infants. There is as yet no effective treatment. Although a carrier test is available, currently there is disagreement among professional medical societies who proffer standards of care as to whether or not carrier screening for spinal muscular atrophy should be offered as part of routine reproductive care. This leaves health care providers without clear guidance. In fall 2009, a meeting was held by National Institutes of Health to examine the scientific basis for spinal muscular atrophy carrier screening and to consider the issues that accompany such screening. In this article, the meeting participants summarize the discussions and conclude that pan-ethnic carrier screening for spinal muscular atrophy is technically feasible and that the specific study of implementing a spinal muscular atrophy carrier screening program raises broader issues about determining the scope and specifics of carrier screening in general. PMID:20808230

  11. Seronegative Intestinal Villous Atrophy: A Diagnostic Challenge

    Directory of Open Access Journals (Sweden)

    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.

  12. Cerebellar atrophy in an epileptic child: is it due to phenytoin?

    Directory of Open Access Journals (Sweden)

    Ahuja S

    2000-10-01

    Full Text Available A four and half year old epileptic child on phenytoin therapy since one year presented with signs of cerebellar dysfunction. Serum phenytoin level was high (33 mcg/ml and computerised tomographic scan of the brain showed severe generalised cerebellar atrophy. The cerebellar signs represented drug over dosage and toxicity and persisted long after omission of phenytoin.

  13. dp53 Restrains ectopic neural stem cell formation in the Drosophila brain in a non-apoptotic mechanism involving Archipelago and cyclin E.

    Directory of Open Access Journals (Sweden)

    Yingshi Ouyang

    Full Text Available Accumulating evidence suggests that tumor-initiating stem cells or cancer stem cells (CSCs possibly originating from normal stem cells may be the root cause of certain malignancies. How stem cell homeostasis is impaired in tumor tissues is not well understood, although certain tumor suppressors have been implicated. In this study, we use the Drosophila neural stem cells (NSCs called neuroblasts as a model to study this process. Loss-of-function of Numb, a key cell fate determinant with well-conserved mammalian counterparts, leads to the formation of ectopic neuroblasts and a tumor phenotype in the larval brain. Overexpression of the Drosophila tumor suppressor p53 (dp53 was able to suppress ectopic neuroblast formation caused by numb loss-of-function. This occurred in a non-apoptotic manner and was independent of Dacapo, the fly counterpart of the well-characterized mammalian p53 target p21 involved in cellular senescence. The observation that dp53 affected Edu incorporation into neuroblasts led us to test the hypothesis that dp53 acts through regulation of factors involved in cell cycle progression. Our results show that the inhibitory effect of dp53 on ectopic neuroblast formation was mediated largely through its regulation of Cyclin E (Cyc E. Overexpression of Cyc E was able to abrogate dp53's ability to rescue numb loss-of-function phenotypes. Increasing Cyc E levels by attenuating Archipelago (Ago, a recently identified transcriptional target of dp53 and a negative regulator of Cyc E, had similar effects. Conversely, reducing Cyc E activity by overexpressing Ago blocked ectopic neuroblast formation in numb mutant. Our results reveal an intimate connection between cell cycle progression and NSC self-renewal vs. differentiation control, and indicate that p53-mediated regulation of ectopic NSC self-renewal through the Ago/Cyc E axis becomes particularly important when NSC homeostasis is perturbed as in numb loss-of-function condition. This has

  14. Postnatal Development of Brain-Derived Neurotrophic Factor (BDNF) and Tyrosine Protein Kinase B (TrkB) Receptor Immunoreactivity in Multiple Brain Stem Respiratory-Related Nuclei of the Rat

    Science.gov (United States)

    Liu, Qiuli; Wong-Riley, Margaret T.T.

    2013-01-01

    Previously, we found a transient imbalance between suppressed excitation and enhanced inhibition in the respiratory network of the rat around postnatal days (P) 12–13, a critical period when the hypoxic ventilatory response is at its weakest. The mechanism underlying the imbalance is poorly understood. Brain-derived neurotrophic factor (BDNF) and its tyrosine protein kinase B (TrkB) receptors are known to potentiate glutamatergic and attenuate gamma-aminobutyric acid (GABA)ergic neurotransmission, and BDNF is essential for respiratory development. We hypothesized that the excitation-inhibition imbalance during the critical period stemmed from a reduced expression of BDNF and TrkB at that time within respiratory-related nuclei of the brain stem. An in-depth, semiquantitative immunohistochemical study was undertaken in seven respiratory-related brain stem nuclei and one nonrespiratory nucleus in P0–21 rats. The results indicate that the expressions of BDNF and TrkB: 1) in the pre-Bötzinger complex, nucleus ambiguus, commissural and ventrolateral subnuclei of solitary tract nucleus, and retrotrapezoid nucleus/parafacial respiratory group were significantly reduced at P12, but returned to P11 levels by P14; 2) in the lateral paragigantocellular nucleus and parapyramidal region were increased from P0 to P7, but were strikingly reduced at P10 and plateaued thereafter; and 3) in the nonrespiratory cuneate nucleus showed a gentle plateau throughout the first 3 post-natal weeks, with only a slight decline of BDNF expression after P11. Thus, the significant downregulation of both BDNF and TrkB in respiratory-related nuclei during the critical period may form the basis of, or at least contribute to, the inhibitory-excitatory imbalance within the respiratory network during this time. PMID:22678720

  15. 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.

  16. Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Elskamp, I.J. van den; Boden, B.; Barkhof, F. [VU University Medical Center, Department of Radiology, MS Center Amsterdam, Amsterdam (Netherlands); Dattola, V. [VU University Medical Center, Department of Radiology, MS Center Amsterdam, Amsterdam (Netherlands); University of Messina, Department of Neurosciences, Psychiatric and Anaesthesiological Sciences, Messina (Italy); Knol, D.L. [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Filippi, M. [Scientific Institute and University Ospedale San Raffaele, Neuroimaging Research Unit, Milan (Italy); Kappos, L. [University Hospital, University of Basel, Department of Neurology, Basel (Switzerland); Fazekas, F. [Medical University of Graz, Department of Neurology, Graz (Austria); Wagner, K. [Bayer-Schering Pharma, Berlin (Germany); Pohl, C. [Bayer-Schering Pharma, Berlin (Germany); University Hospital Bonn, Department of Neurology, Bonn (Germany); Sandbrink, R. [Bayer-Schering Pharma, Berlin (Germany); Heinrich-Heine-University Dusseldorf, Department of Neurology, Dusseldorf (Germany); Polman, C.H. [VU University Medical Center, Department of Neurology, MS Center Amsterdam, Amsterdam (Netherlands); Uitdehaag, B.M.J. [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); VU University Medical Center, Department of Neurology, MS Center Amsterdam, Amsterdam (Netherlands)

    2010-10-15

    Cerebral atrophy is a compound measure of the neurodegenerative component of multiple sclerosis (MS) and a conceivable outcome measure for clinical trials monitoring the effect of neuroprotective agents. In this study, we evaluate the rate of cerebral atrophy in a 6-month period, investigate the predictive and explanatory value of other magnetic resonance imaging (MRI) measures in relation to cerebral atrophy, and determine sample sizes for future short-term clinical trials using cerebral atrophy as primary outcome measure. One hundred thirty-five relapsing-remitting multiple sclerosis patients underwent six monthly MRI scans from which the percentage brain volume change (PBVC) and the number and volume of gadolinium (Gd)-enhancing lesions, T2 lesions, and persistent black holes (PBH) were determined. By means of multiple linear regression analysis, the relationship between focal MRI variables and PBVC was assessed. Sample size calculations were performed for all patients and subgroups selected for enhancement or a high T2 lesion load at baseline. A significant atrophy occurred over 6 months (PBVC = -0.33%, SE = 0.061, p < 0.0001). The number of baseline T2 lesions (p = 0.024), the on-study Gd-enhancing lesion volume (p = 0.044), and the number of on-study PBHs (p = 0.003) were associated with an increased rate of atrophy. For a 50% decrease in rate of atrophy, the sample size calculations showed that approximately 283 patients per arm are required in an unselected sampled population and 185 patients per arm are required in a selected population. Within a 6-month period, significant atrophy can be detected and on-study associations of PBVC and PBHs emphasizes axonal loss to be a driving mechanism. Application as primary outcome measure in short-term clinical trials with feasible sample size requires a potent drug to obtain sufficient power. (orig.)

  17. Intracerebral adult stem cells transplantation increases brain-derived neurotrophic factor levels and protects against phencyclidine-induced social deficit in mice

    Science.gov (United States)

    Barzilay, R; Ben-Zur, T; Sadan, O; Bren, Z; Taler, M; Lev, N; Tarasenko, I; Uzan, R; Gil-Ad, I; Melamed, E; Weizman, A; Offen, D

    2011-01-01

    Stem cell-based regenerative therapy is considered a promising cellular therapeutic approach for the patients with incurable brain diseases. Mesenchymal stem cells (MSCs) represent an attractive cell source for regenerative medicine strategies for the treatment of the diseased brain. Previous studies have shown that these cells improve behavioral deficits in animal models of neurological disorders such as Parkinson's and Huntington's diseases. In the current study, we examined the capability of intracerebral human MSCs transplantation (medial pre-frontal cortex) to prevent the social impairment displayed by mice after withdrawal from daily phencyclidine (PCP) administration (10 mg kg−1 daily for 14 days). Our results show that MSCs transplantation significantly prevented the PCP-induced social deficit, as assessed by the social preference test. In contrast, the PCP-induced social impairment was not modified by daily clozapine treatment. Tissue analysis revealed that the human MSCs survived in the mouse brain throughout the course of the experiment (23 days). Significantly increased cortical brain-derived neurotrophic factor levels were observed in the MSCs-treated group as compared with sham-operated controls. Furthermore, western blot analysis revealed that the ratio of phosphorylated Akt to Akt was significantly elevated in the MSCs-treated mice compared with the sham controls. Our results demonstrate that intracerebral transplantation of MSCs is beneficial in attenuating the social deficits induced by sub-chronic PCP administration. We suggest a novel therapeutic approach for the treatment of schizophrenia-like negative symptoms in animal models of the disorder. PMID:22832353

  18. Feasibility of the Medial Temporal lobe Atrophy index (MTAi and derived methods for measuring atrophy of the medial temporal lobe

    Directory of Open Access Journals (Sweden)

    Francisco eConejo Bayón

    2014-11-01

    Full Text Available Introduction: the Medial Temporal-lobe Atrophy index (MTAi, 2D-Medial Temporal Atrophy (2D-MTA, yearly rate of MTA (yrRMTA and yearly rate of relative MTA (yrRMTA are simple protocols for measuring the relative extent of atrophy in the MTL in relation to the global brain atrophy. Albeit preliminary studies showed interest of these methods in the diagnosis of AD, FTLD and correlation with cognitive impairment in PD, formal feasibility and validity studies remained pending. As a first step, we aimed to assess the feasibility. Mainly, we aimed to assess the reproducibility of measuring the areas needed to compute these indices. We also aimed to assess the efforts needed to start using these methods correctly. Methods: a series of 290 1.5T-MRI studies from 230 subjects ranging 65-85 years old who had been studied for cognitive impairment were used in this study. Six inexperienced tracers (IT plus one experienced tracer (ET traced the three areas needed to compute the indices. Finally, tracers underwent a short survey on their experience learning to compute the MTAi and experience of usage, including items relative to training time needed to understand and apply the MTAi, time to perform a study after training and overall satisfaction. Results: learning to trace the areas needed to compute the MTAi and derived methods is quick and easy. Results indicate very good intrarater ICC for the MTAi, good intrarater ICC for the 2D-MTA, yrMTA and yrRMTA and also good interrater ICC for the MTAi, 2D-MTA, yrMTA and yrRMTA.Conclusion: our data support that MTAi and derived methods (2D-MTA, yrMTA and yrRTMA have good to very good intrarater and interrater reproducibility and may be easily implemented in clinical practice even if new users have no experience tracing the area of regions of interest.

  19. Neural Stem Cells Secreting Anti-HER2 Antibody Improve Survival in a Preclinical Model of HER2 Overexpressing Breast Cancer Brain Metastases.

    Science.gov (United States)

    Kanojia, Deepak; Balyasnikova, Irina V; Morshed, Ramin A; Frank, Richard T; Yu, Dou; Zhang, Lingjiao; Spencer, Drew A; Kim, Julius W; Han, Yu; Yu, Dihua; Ahmed, Atique U; Aboody, Karen S; Lesniak, Maciej S

    2015-10-01

    The treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer has been revolutionized by trastuzumab. However, longer survival of these patients now predisposes them to forming HER2 positive brain metastases, as the therapeutic antibodies cannot cross the blood brain barrier. The current oncologic repertoire does not offer a rational, nontoxic targeted therapy for brain metastases. In this study, we used an established human neural stem cell line, HB1.F3 NSCs and generated a stable pool of cells secreting a high amount of functional full-length anti-HER2 antibody, equivalent to trastuzumab. Anti-HER2Ab secreted by the NSCs (HER2Ab-NSCs) specifically binds to HER2 overexpressing human breast cancer cells and inhibits PI3K-Akt signaling. This translates to HER2Ab-NSC inhibition of breast cancer cell growth in vitro. Preclinical in vivo experiments using HER2Ab overexpressing NSCs in a breast cancer brain metastases (BCBM) mouse model demonstrate that intracranial injection of HER2Ab-NSCs significantly improves survival. In effect, these NSCs provide tumor localized production of HER2Ab, minimizing any potential off-target side effects. Our results establish HER2Ab-NSCs as a novel, nontoxic, and rational therapeutic approach for the successful treatment of HER2 overexpressing BCBM, which now warrants further preclinical and clinical investigation. © 2015 AlphaMed Press.

  20. The effects of grafted mesenchymal stem cells labeled with iron oxide or cobalt-zinc-iron nanoparticles on the biological macromolecules of rat brain tissue extracts.

    Science.gov (United States)

    Novotna, Bozena; Herynek, Vit; Rossner, Pavel; Turnovcova, Karolina; Jendelova, Pavla

    2017-01-01

    Rat mesenchymal stem cells (rMSCs) labeled with 1) poly-l-lysine-coated superparamagnetic iron oxide nanoparticles or 2) silica-coated cobalt-zinc-iron nanoparticles were implanted into the left brain hemisphere of rats, to assess their effects on the levels of oxidative damage to biological macromolecules in brain tissue. Controls were implanted with unlabeled rMSCs. Animals were sacrificed 24 hours or 4 weeks after the treatment, and the implantation site along with the surrounding tissue was isolated from the brain. At the same intervals, parallel groups of animals were scanned in vivo by magnetic resonance imaging (MRI). The comet assay with enzymes of excision DNA repair (endonuclease III and formamidopyrimidine-DNA glycosylase) was used to analyze breaks and oxidative damage to DNA in the brain tissue. Oxidative damage to proteins and lipids was determined by measuring the levels of carbonyl groups and 15-F2t-isoprostane (enzyme-linked immunosorbent assay). MRI displayed implants of labeled cells as extensive hypointense areas in the brain tissue. In histological sections, the expression of glial fibrillary acidic protein and CD68 was analyzed to detect astrogliosis and inflammatory response. Both contrast labels caused a similar response in the T2-weighted magnetic resonance (MR) image and the signal was clearly visible within 4 weeks after implantation of rMSCs. No increase of oxidative damage to DNA, lipids, or proteins over the control values was detected in any sample of brain tissue from the treated animals. Also, immunohistochemistry did not indicate any serious tissue impairment around the graft. Both tested types of nanoparticles appear to be prospective and safe labels for tracking the transplanted cells by MR.

  1. The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor.

    Directory of Open Access Journals (Sweden)

    Suely Maymone de Melo

    Full Text Available Glioblastoma (GBM is an infiltrative tumor that is difficult to eradicate. Treating GBM with mesenchymal stem cells (MSCs that have been modified with the HSV-Tk suicide gene has brought significant advances mainly because MSCs are chemoattracted to GBM and kill tumor cells via a bystander effect. To use this strategy, abundantly present adipose-tissue-derived mesenchymal stem cells (AT-MSCs were evaluated for the treatment of GBM in mice. AT-MSCs were prepared using a mechanical protocol to avoid contamination with animal protein and transduced with HSV-Tk via a lentiviral vector. The U-87 glioblastoma cells cultured with AT-MSC-HSV-Tk died in the presence of 25 or 50 μM ganciclovir (GCV. U-87 glioblastoma cells injected into the brains of nude mice generated tumors larger than 3.5 mm2 after 4 weeks, but the injection of AT-MSC-HSV-Tk cells one week after the U-87 injection, combined with GCV treatment, drastically reduced tumors to smaller than 0.5 mm2. Immunohistochemical analysis of the tumors showed the presence of AT-MSC-HSV-Tk cells only within the tumor and its vicinity, but not in other areas of the brain, showing chemoattraction between them. The abundance of AT-MSCs and the easier to obtain them mechanically are strong advantages when compared to using MSCs from other tissues.

  2. Effective treatment of glioblastoma requires crossing the blood-brain barrier and targeting tumors including cancer stem cells: The promise of nanomedicine.

    Science.gov (United States)

    Kim, Sang-Soo; Harford, Joe B; Pirollo, Kathleen F; Chang, Esther H

    2015-12-18

    Glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain tumor. Both therapeutic resistance and restricted permeation of drugs across the blood-brain barrier (BBB) play a major role in the poor prognosis of GBM patients. Accumulated evidence suggests that in many human cancers, including GBM, therapeutic resistance can be attributed to a small fraction of cancer cells known as cancer stem cells (CSCs). CSCs have been shown to have stem cell-like properties that enable them to evade traditional cytotoxic therapies, and so new CSC-directed anti-cancer therapies are needed. Nanoparticles have been designed to selectively deliver payloads to relevant target cells in the body, and there is considerable interest in the use of nanoparticles for CSC-directed anti-cancer therapies. Recent advances in the field of nanomedicine offer new possibilities for overcoming CSC-mediated therapeutic resistance and thus significantly improving management of GBM. In this review, we will examine the current nanomedicine approaches for targeting CSCs and their therapeutic implications. The inhibitory effect of various nanoparticle-based drug delivery system towards CSCs in GBM tumors is the primary focus of this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Curved reformat of the paediatric brain MRI into a 'flat-earth map' - standardised method for demonstrating cortical surface atrophy resulting from hypoxic-ischaemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, Ewan [Bristol Royal Hospital for Children, Department of Pediatric Radiology, Bristol (United Kingdom); Andronikou, Savvas [Bristol Royal Hospital for Children, Department of Pediatric Radiology, Bristol (United Kingdom); University of Bristol, CRICBristol, Bristol (United Kingdom); Vedajallam, Schadie; Chacko, Anith; Thai, Ngoc Jade [University of Bristol, CRICBristol, Bristol (United Kingdom)

    2016-09-15

    Hypoxic-ischaemic encephalopathy is optimally imaged with brain MRI in the neonatal period. However neuroimaging is often also performed later in childhood (e.g., when parents seek compensation in cases of alleged birth asphyxia). We describe a standardised technique for creating two curved reconstructions of the cortical surface to show the characteristic surface changes of hypoxic-ischaemic encephalopathy in children imaged after the neonatal period. The technique was applied for 10 cases of hypoxic-ischaemic encephalopathy and also for age-matched healthy children to assess the visibility of characteristic features of hypoxic-ischaemic encephalopathy. In the abnormal brains, fissural or sulcal widening was seen in all cases and ulegyria was identifiable in 7/10. These images could be used as a visual aid for communicating MRI findings to clinicians and other interested parties. (orig.)

  4. Rapidly worsening bulbar symptoms in a patient with spinobulbar muscular atrophy

    Directory of Open Access Journals (Sweden)

    Montserrat Diaz-Abad

    2013-12-01

    Full Text Available X-linked spinobulbar muscular atrophy (Kennedy’s disease affects muscles and motor neurons, manifesting as weakness and wasting of bulbar, facial, and proximal limb muscles due to loss of anterior horn cells in the brain and spinal cord. We present the case of a patient with X-linked spinobulbar muscular atrophy with rapidly worsening bulbar symptoms caused by laryngopharyngeal irritation associated with a viral upper respiratory tract infection, seasonal allergies and laryngopharyngeal reflux, who dramatically improved with multimodality therapy.

  5. Novel SIL1 mutations cause cerebellar ataxia and atrophy in a French-Canadian family.

    Science.gov (United States)

    Noreau, Anne; La Piana, Roberta; Marcoux, Camille; Dion, Patrick A; Brais, Bernard; Bernard, Geneviève; Rouleau, Guy A

    2015-10-01

    Two French-Canadian sibs with cerebellar ataxia and dysarthria were seen in our neurogenetics clinic. The older brother had global developmental delay and spastic paraplegia. Brain MRIs from these two affected individuals showed moderate to severe cerebellar atrophy. To identify the genetic basis for their disease, we conducted a whole exome sequencing (WES) investigation using genomic DNA prepared from the affected sibs and their healthy father. We identified two mutations in the SIL1 gene, which is reported to cause Marinesco-Sjögren syndrome. This study emphasizes how the diagnosis of patients with ataxic gait and cerebellar atrophy may benefit from WES to identify the genetic cause of their condition.

  6. Brain computed tomography of the hypertensive patients

    Energy Technology Data Exchange (ETDEWEB)

    Bae, W. K.; Park, C. K.; Cho, O. K.; Hahm, C. K. [College of Medicine, Hanyang University, Seoul (Korea, Republic of)

    1980-12-15

    Now a day, hypertension is more increasing in frequency and ranked the top of the causes of death in Korea and other nations. Most of cerebrovascular accidents in hypertensive patients are composed of vascular occlusive changes and hemorrhages. In cerebral angiogram, we can only detect occlusion of large artery and large mass effect from hematoma or cerebral infarction without identification of its entity. The computed tomogram, however, is the best way for evaluation of cerebrovascular diseases including detection of nature, location, amount, and associated changes. This study includes evaluation of computed tomograms of 106 patients with hypertension during the period of 17 months from Feb. 1979 to June 1980 in the department of radiology, college of Medicine, Hanyang University. The results were as follows. 1. Age distribution of the total 106 patients was broad ranging from 25 years to 76 years. 67.9% of patients were over the age of 50. The male and female sex ratio was 3:2. 2. 28 out of 106 patients were normal and 78 patients revealed abnormal on C. T. findings; those were intracranial hemorrhage (35 patients), cerebral infarction (32 patients) and brain atrophy (11 patients). 3. All of the intracranial hemorrhage except one were intracerebral hemorrhage; those were located in the cerebral hemisphere (19 patients), basal ganglia (15 patients) and brain stem (1 patient). The except one case of intracranial hemorrhage was subdural hematoma. 7 patients of intraventricular hemorrhage and 1 patient of subarachnoid hemorrhage were combined with intracerebral hemorrhage. 2/3 of patients who had hemorrhage in cerebral hemisphere revealed lesions in the parietal and temporal lobes. 4. In cases of cerebral infarction, the cerebral hemisphere was most common site of lesion (20 cases), and the next was basal ganglia (11 cases). Most of the infarcts in cerebral hemisphere were located in the parietal and temporal lobes. The left basal ganglia was more commonly involved

  7. Auditory brain-stem response, CT and MR imaging in a family with classical type Pelizaeus-Merzbacher Disease

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    Shiomi, M.; Ookuni, H.; Sugita, T.

    1987-05-01

    A family in which 5 males in successive generations were clinically suspected to be affected with the classical X-linked recessive form of Pelizaeus-Merzbacher disease (PMD) is presented. Two brothers and their maternal uncle were examined by one of the authors (MS). In two brothers, aged 3 years and 2 years, the disease became obvious within a month after birth with nystagmus and head tremor. Head control and sitting were achieved at the age of 18 months at which time they began to speak. They could not stand nor walk without support. They had dysmetria, weakness and hyper-reflexia of lower extremities, and mild mental retardation. Their maternal uncle, aged 37 years, showed psychomotor retardation from birth and subsequently developed spastic paraplegia. He had been able to walk with crutches until adolescence. He had dysmetria, scanning speech, athetoid posture of fingers and significant intellectual deficits. Auditory brainstem response in both brothers revealed well defined waves I and II, low amplitude wave III and an absence of all subsequent components. CT demonstrated mild cerebral atrophy in the elder brother and was normal in the younger brother, but in their uncle, CT showed atrophy of the brainstem, cerebellum and cerebrum, and low density of the white matter of the centrum semiovale. MRI was performed in both brothers. Although the brainstem, the internal capsule and the thalamus were myelinated, the myelination in the subcortical white matter was restricted to periventricular regions on IR sequence scans. On SE sequence, the subcortical white matter was imaged as a brighter area than the cerebral cortex. These results demonstrate that the degree of myelination in these patients was roughly equal to that of 3-to 6-month old infants.

  8. Fatal outcome after b