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  1. Abnormal glucose tolerance and lipid abnormalities in Indian ...

    African Journals Online (AJOL)

    Discussion. Regardless of varying diagnostic classification, abnormal glucose tolerance is a well-documented risk factor. 16 Abnormalities in. Because ofthe small number offemale MI survivors, the effect of obesity and abnormal glucose tolerance on lipid levels was studied in the male patients only. There was no significant.

  2. Measuring brain glucose phosphorylation with labeled glucose

    International Nuclear Information System (INIS)

    Brondsted, H.E.; Gjedde, A.

    1988-01-01

    This study tested whether glucose labeled at the C-6 position generates metabolites that leave brain so rapidly that C-6-labeled glucose cannot be used to measure brain glucose phosphorylation (CMRGlc). In pentobarbital-anesthetized rats, the parietal cortex uptake of [ 14 C]glucose labeled in the C-6 position was followed for times ranging from 10 s to 60 min. We subtracted the observed radioactivity from the radioactivity expected with no loss of labeled metabolites from brain by extrapolation of glucose uptake in an initial period when loss was negligible. The observed radioactivity was a monoexponentially declining function of the total radioactivity expected in the absence of metabolite loss. The constant of decline was 0.0077.min-1 for parietal cortex. Metabolites were lost from the beginning of the experiment. However, with correction for the loss of labeled metabolites, it was possible to determine an average CMRGlc between 4 and 60 min of circulation of 64 +/- 4 (SE; n = 49) mumol.hg-1.min-1

  3. Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production

    OpenAIRE

    Lam, Tony K.T.

    2007-01-01

    Brain glucose-sensing mechanisms are implicated in the regulation of feeding behavior and hypoglycemic-induced hormonal counter-regulation. This commentary discusses recent findings indicating that the brain senses glucose to regulate both hepatic glucose and lipid production.

  4. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    International Nuclear Information System (INIS)

    Nam, H. Y.; Seo, G. T.; Lee, J. S.; Kim, S. C.; Kim, I. J.; Kim, Y. K.; Jeon, S. M.

    2007-01-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with adolescent idiopathic scoliosis. The mean mini-mental status exam score in the congenital scoliosis group was significantly lower than that in the adolescent idiopathic scoliosis group. Group analysis found that various brain areas of patients with congenital scoliosis showed glucose hypometabolisms in the left prefrontal cortex (Brodmann area 10), right orbitofrontal cortex (Brodmann area 11), left dorsolateral prefrontal cortex (Brodmann area 9), left anterior cingulate gyrus (Brodmann area 24) and pulvinar of the left thalamus. From this study, we could find the metabolic abnormalities of brain in patients with congenital scoliosis and suggest the possible role of voxel-based analysis of brain fluorodeoxyglucose positron emission tomography

  5. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    Energy Technology Data Exchange (ETDEWEB)

    Nam, H. Y.; Seo, G. T.; Lee, J. S.; Kim, S. C.; Kim, I. J.; Kim, Y. K.; Jeon, S. M. [Pusan National University Hospital, Pusan (Korea, Republic of)

    2007-07-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with adolescent idiopathic scoliosis. The mean mini-mental status exam score in the congenital scoliosis group was significantly lower than that in the adolescent idiopathic scoliosis group. Group analysis found that various brain areas of patients with congenital scoliosis showed glucose hypometabolisms in the left prefrontal cortex (Brodmann area 10), right orbitofrontal cortex (Brodmann area 11), left dorsolateral prefrontal cortex (Brodmann area 9), left anterior cingulate gyrus (Brodmann area 24) and pulvinar of the left thalamus. From this study, we could find the metabolic abnormalities of brain in patients with congenital scoliosis and suggest the possible role of voxel-based analysis of brain fluorodeoxyglucose positron emission tomography.

  6. The prevalence and risk factors of abnormal glucose tolerance ...

    African Journals Online (AJOL)

    BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrinopathy amongst women in the reproductive age worldwide. Abnormal glucose tolerance (AGT) is common amongst women with PCOS. The prevalence of abnormal glucose tolerance amongst Nigerian women with PCOS has not been investigated.

  7. Abnormal brain glucose metabolism and depressive mood in patients with pre-dialytic chronic kidney disease: SPM analysis of F-18 FDG positron emission tomography

    International Nuclear Information System (INIS)

    Jun, Sung Min; Song, Sang Heon; Kim, Seong Jang; Kim, Ji Hoon; Kwak, Ihm Soo; Kim, In Ju; Kim, Yong Ki

    2007-01-01

    The aim of this study was to investigate the relationship between depressive mood and pre-dialytic CKD, to localize and quantify depressive mood -related lesions in pre-dialytic CKD patients through statistical parametric mapping (SPM) analysis of brain positron emission tomography (PET), and to examine the usefulness of brain PET for early detection and proper treatment of depressive mood. Twenty one patients with stage 5 CKD and 22 healthy volunteers were analyzed by depressive mood assessment and statistical parametric mapping (SPM) analysis of 18F-FDG PET. Depressive mood assessment was done by Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). The largest clusters were areas including precentral gyrus, prefrontal cortex, and anterior cingulated cortex of left hemisphere. Other clusters were left transverse temporal gyrus, left superior temporal gyrus, right prefrontal cortex, right dorsolateral prefrontal cortex (BA 46, 44), right inferior frontal gyrus, right inferior parietal lobule, left angular gyrus. In addition, correlation was found between hypometabolized areas and HDRS scores of CKD patients in right prefrontal cortex (BA 11) and right anterior cingulated gyrus (BA 24). In conclusion, this study demonstrated specific depressive mood-related abnormal metabolic lesion. Interestingly, in CKD patients with severe depressive mood, cerebral metabolism was similar to that of MDD

  8. Abnormal glucose tolerance and lipid abnormalities in Indian ...

    African Journals Online (AJOL)

    Glucose tolerance and lipid levels in a random sample of 103 Indian patients (96 males and 7 females) with coronary artery disease (CAD) aged between 20 and 55 years were compared with those in a healthy Indian control group matched as regards age and sex. Previous episodes of myocardial infarction were taken as ...

  9. Schizophrenia and abnormal brain network hubs.

    Science.gov (United States)

    Rubinov, Mikail; Bullmore, Ed

    2013-09-01

    Schizophrenia is a heterogeneous psychiatric disorder of unknown cause or characteristic pathology. Clinical neuroscientists increasingly postulate that schizophrenia is a disorder of brain network organization. In this article we discuss the conceptual framework of this dysconnection hypothesis, describe the predominant methodological paradigm for testing this hypothesis, and review recent evidence for disruption of central/hub brain regions, as a promising example of this hypothesis. We summarize studies of brain hubs in large-scale structural and functional brain networks and find strong evidence for network abnormalities of prefrontal hubs, and moderate evidence for network abnormalities of limbic, temporal, and parietal hubs. Future studies are needed to differentiate network dysfunction from previously observed gray- and white-matter abnormalities of these hubs, and to link endogenous network dysfunction phenotypes with perceptual, behavioral, and cognitive clinical phenotypes of schizophrenia.

  10. Brain Volume Abnormalities in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-11-01

    Full Text Available Regional brain volumes have been compared at initial MRI scans and their change over time in 152 medicated and previously unmedicated male and female patients (age range, 5-18 years with attention-deficit/hyperactivity disorder (ADHD and 139 age- and sex-matched healthy controls.

  11. Asymmetry of cerebral glucose metabolism in very low-birth-weight infants without structural abnormalities.

    Directory of Open Access Journals (Sweden)

    Jae Hyun Park

    Full Text Available Thirty-six VLBW infants who underwent F-18 fluorodeoxyglucose (F-18 FDG brain PET and MRI were prospectively enrolled, while infants with evidence of parenchymal brain injury on MRI were excluded. The regional glucose metabolic ratio and asymmetry index were calculated. The asymmetry index more than 10% (right > left asymmetry or less than -10% (left > right asymmetry were defined as abnormal. Regional cerebral glucose metabolism were compared between right and left cerebral hemispheres, and between the following subgroups: multiple gestations, premature rupture of membrane, bronchopulmonary dysplasia, and low-grade intraventricular hemorrhage.In the individual analysis, 21 (58.3% of 36 VLBW infants exhibited asymmetric cerebral glucose metabolism. Fifteen infants (41.7% exhibited right > left asymmetry, while six (16.7% exhibited left > right asymmetry. In the regional analysis, right > left asymmetry was more extensive than left > right asymmetry. The metabolic ratio in the right frontal, temporal, and occipital cortices and right thalamus were significantly higher than those in the corresponding left regions. In the subgroup analyses, the cerebral glucose metabolism in infants with multiple gestations, premature rupture of membrane, bronchopulmonary dysplasia, or low-grade intraventricular hemorrhage were significantly lower than those in infants without these.VLBW infants without structural abnormalities have asymmetry of cerebral glucose metabolism. Decreased cerebral glucose metabolism are noted in infants with neurodevelopmental risk factors. F-18 FDG PET could show microstructural abnormalities not detected by MRI in VLBW infants.

  12. Continuous Glucose Monitoring in Patients with Abnormal Glucose Tolerance during Pregnancy: A Case Series

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    Mie Tonoike

    2016-01-01

    Full Text Available Abnormal glucose tolerance during pregnancy is associated with perinatal complications. We used continuous glucose monitoring (CGM in pregnant women with glucose intolerance to achieve better glycemic control and to evaluate the maternal glucose fluctuations. We also used CGM in women without glucose intolerance (the control cases. Furthermore, the standard deviation (SD and mean amplitude of glycemic excursions (MAGE were calculated for each case. For the control cases, the glucose levels were tightly controlled within a very narrow range; however, the SD and MAGE values in pregnant women with glucose intolerance were relativity high, suggesting postprandial hyperglycemia. Our results demonstrate that pregnant women with glucose intolerance exhibited greater glucose fluctuations compared with the control cases. The use of CGM may help to improve our understanding of glycemic patterns and may have beneficial effects on perinatal glycemic control, such as the detection of postprandial hyperglycemia in pregnant women.

  13. Brain Abnormalities in Neuromyelitis Optica Spectrum Disorder

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    Woojun Kim

    2012-01-01

    Full Text Available Neuromyelitis optica (NMO is an idiopathic inflammatory syndrome of the central nervous system that is characterized by severe attacks of optic neuritis (ON and myelitis. Until recently, NMO was considered a disease without brain involvement. However, since the discovery of NMO-IgG/antiaqaporin-4 antibody, the concept of NMO was broadened to NMO spectrum disorder (NMOSD, and brain lesions are commonly recognized. Furthermore, some patients present with brain symptoms as their first manifestation and develop recurrent brain symptoms without ON or myelitis. Brain lesions with characteristic locations and configurations can be helpful in the diagnosis of NMOSD. Due to the growing recognition of brain abnormalities in NMOSD, these have been included in the NMO and NMOSD diagnostic criteria or guidelines. Recent technical developments such as diffusion tensor imaging, MR spectroscopy, and voxel-based morphometry reveal new findings related to brain abnormalities in NMOSD that were not identified using conventional MRI. This paper focuses on the incidence and characteristics of the brain lesions found in NMOSD and the symptoms that they cause. Recent studies using advanced imaging techniques are also introduced.

  14. Dietary Patterns and Glucose Tolerance Abnormalities in Chinese Adults

    NARCIS (Netherlands)

    He, Y.; Ma, G.; Zhai, F.; Li, Y.; Hu, Y.; Feskens, E.J.M.; Yang, X.

    2009-01-01

    OBJECTIVE To investigate the association of the dietary pattern with the presence of newly diagnosed glucose tolerance abnormalities among Chinese adults. RESEARCH DESIGN AND METHODS A total of 20,210 adults aged 45–69 years from the 2002 China National Nutrition and Health Survey were included.

  15. Migraine and structural abnormalities in the brain

    DEFF Research Database (Denmark)

    Hougaard, Anders; Amin, Faisal Mohammad; Ashina, Messoud

    2014-01-01

    PURPOSE OF REVIEW: The aim is to provide an overview of recent studies of structural brain abnormalities in migraine and to discuss the potential clinical significance of their findings. RECENT FINDINGS: Brain structure continues to be a topic of extensive research in migraine. Despite advances...... in neuroimaging techniques, it is not yet clear if migraine is associated with grey matter changes. Recent large population-based studies sustain the notion of increased prevalence of white matter abnormalities in migraine, and possibly of silent infarct-like lesions. The clinical relevance of this association...... is not clear. Structural changes are not related to cognitive decline, but a link to an increased risk of stroke, especially in patients with aura, cannot be ruled out. SUMMARY: Migraine may be a risk factor for structural changes in the brain. It is not yet clear how factors such as migraine sub-type, attack...

  16. Abnormalities of glucose metabolism in spontaneously hypertensive rats

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    Gouveia L.M.F.B.

    2000-01-01

    Full Text Available Abnormalities in glucose metabolism and insulin action are frequently detected in patients with essential hypertension. Spontaneously hypertensive rats (SHR have been used as an experimental model to understand this pathological condition. The objective of the present study was to assess glucose metabolism and insulin action in SHR and Wistar rats under fed and fasting conditions. Peripheral glucose utilization was estimated by kinetic studies with [6-³H]-glucose and gluconeogenetic activity was measured during continuous [14C]-bicarbonate infusion. Plasma glucose levels were higher in the SHR group. Plasma insulin levels in the fed state were higher in the SHR group (99.8 ± 6.5 µM than in the control group (70.4 ± 3.6 µM. Muscle glycogen content was reduced in SHR compared to control under the various experimental conditions. Peripheral glucose utilization was slightly lower in the SHR group in the fed state (8.72 ± 0.55 vs 9.52 ± 0.80 mg kg-1 min-1 in controls. Serum free fatty acid levels, hepatic glycogen levels, hepatic phosphoenolpyruvate carboxykinase activity and gluconeogenetic activity were similar in the two groups. The presence of hyperglycemia and hyperinsulinemia and the slightly reduced peripheral glucose utilization suggest the presence of resistance to the action of insulin in peripheral tissues of SHR. Hepatic gluconeogenesis does not seem to contribute to the metabolic alterations detected in these animals.

  17. Abnormal oral glucose tolerance and glucose malabsorption after vagotomy and pyloroplasty. A tracer method for measuring glucose absorption rates

    International Nuclear Information System (INIS)

    Radziuk, J.; Bondy, D.C.

    1982-01-01

    The mechanisms underlying the abnormal glucose tolerance in patients who had undergone vagotomy and pyloroplasty were investigated by measuring the rates of absorption of ingested glucose and the clearance rate of glucose using tracer methods. These methods are based on labeling a 100-g oral glucose load with [1- 14 C]glucose and measuring glucose clearance using plasma levels of infused [3- 3 H]glucose. The rate of appearance of both ingested and total glucose is then calculated continuously using a two-compartment model of glucose kinetics. It was found that about 30% of the ingested glucose (100 g) failed to appear in the systemic circulation. That this was due to malabsorption was confirmed using breath-hydrogen analysis. The absorption period is short (101 +/- 11 min) compared with normal values but the clearance of glucose is identical to that in control subjects, and it peaks 132 +/- 7 min after glucose loading. The peak plasma insulin values were more than four times higher in patients than in normal subjects, and this may afford an explanation of rates of glucose clearance that are inappropriate for the short absorption period. The combination of glucose malabsorption and this clearance pattern could yield the hypoglycemia that may be observed in patients after gastric surgery

  18. Morphological and glucose metabolism abnormalities in alcoholic Korsakoff's syndrome: group comparisons and individual analyses.

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    Anne-Lise Pitel

    Full Text Available BACKGROUND: Gray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS. Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies. METHODOLOGY/PRINCIPAL FINDINGS: Nine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and (18F-fluorodeoxyglucose positron emission tomography examinations. Using a whole-brain analysis, the between-group comparisons of gray matter and white matter density and relative glucose uptake between patients with KS and controls showed the involvement of both the frontocerebellar and the Papez circuits, including morphological abnormalities in their nodes and connection tracts and probably resulting hypometabolism. The direct comparison of the regional distribution and degree of gray matter hypodensity and hypometabolism within the KS group indicated very consistent gray matter distribution of both abnormalities, with a single area of significant difference in the middle cingulate cortex showing greater hypometabolism than hypodensity. Finally, the analysis of the variability in the individual patterns of brain abnormalities within our sample of KS patients revealed that the middle cingulate cortex was the only brain region showing significant GM hypodensity and hypometabolism in each of our 9 KS patients. CONCLUSIONS/SIGNIFICANCE: These results indicate widespread brain abnormalities in KS including both gray and white matter damage mainly involving two brain networks, namely, the fronto-cerebellar circuit and the Papez circuit. Furthermore, our findings suggest that the middle cingulate cortex may play a key role in the pathophysiology of KS and could be considered as a potential in vivo brain biomarker.

  19. Evidence of brain abnormality in patients with psychogenic nonepileptic seizures.

    NARCIS (Netherlands)

    Reuber, M.; Fernandez, G.S.E.; Bauer, J.; Singh, D.D.; Elger, C.E.

    2002-01-01

    Markers of brain abnormalities in patients with psychogenic nonepileptic seizures (PNES) were studied to explore whether physical brain disorder is associated with an increased risk of PNES. Evidence of epileptiform EEG changes, MRI abnormalities, and neuropsychological (NPS)

  20. Brain MRI abnormalities in neuromyelitis optica

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    Wang Fei, E-mail: feiwang1973@gmail.com [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Liu Yaou, E-mail: asiaeurope80@gmail.com [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Duan Yunyun, E-mail: duanyun2003@sohu.com [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Li Kuncheng, E-mail: kunchengli@yahoo.com.cn [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Education Ministry Key Laboratory for Neurodegenerative Disease, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China)

    2011-11-15

    Objective: The purpose of this study was to explore brain MRI findings in neuromyelitis optica (NMO) and to investigate specific brain lesions with respect to the localization of aquaporin-4 (AQP-4). Materials and methods: Forty admitted patients (36 women) who satisfied the 2006 criteria of Wingerchuk et al. for NMO were included in this study. All patients received a neurological examination and MRI scanning including brain and spinal cord. MRIs were classified as normal, nonspecific, multiple sclerosis-like, typical abnormalities. MS-like lesions were too few to satisfy the Barkhof et al. criteria for MS. Confluent lesions involving high AQP-4 regions were considered typical. Non-enhancing deep white matter lesions other than MS-like lesions or typical lesions were classified as nonspecific. Results: Brain MRI lesions were delineated in 12 patients (25%). Four patients (10%) had hypothalamus, brainstem or periventricle lesions. Six (15%) patients were nonspecific, and 2 (5%) patients had multiple sclerosis-like lesions. Conclusion: Brain MRIs are negative in most NMO, and brain lesions do not exclude the diagnosis of NMO. Hypothalamus, brainstem or periventricle lesions, corresponding to high sites of AQP-4 in the brain, are indicative of lesions of NMO.

  1. Glucose abnormalities in Asian patients with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Bo Q

    2015-11-01

    Full Text Available Qingyan Bo,1 Roberto Orsenigo,2 Junyi Wang,1 Louis Griffel,3 Clifford Brass3 1Beijing Novartis Pharma Co. Ltd., Shanghai, People’s Republic of China; 2Novartis Pharma AG, Basel, Switzerland; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Abstract: Many studies have demonstrated a potential association between type 2 diabetes (T2D and hepatitis C virus infection in Western countries, while similar evidence is limited in Asia. We compared the prevalence of glucose abnormalities (impaired fasting glucose [IFG] and T2D and their risk factors between Asian and non-Asian chronic hepatitis C (CHC patients, and evaluated whether glucose abnormalities impacted the viral responses to peginterferon plus ribavirin treatment (current standard of care in most Asian countries. This study retrospectively analyzed data of 1,887 CHC patients from three Phase II/III studies with alisporivir (DEB025 as treatment for CHC. The chi-square test was used to compare the prevalence of IFG/T2D between Asian and non-Asian CHC patients, and logistic regression was used to adjust for sex, age, and cirrhosis status. Risk factors for IFG/T2D were evaluated using univariate and multivariate analysis. Our results indicated that the prevalence of IFG/T2D was high in both Asian and non-Asian CHC patients (23.0% vs 20.9%, and no significant difference was found between these two populations (adjusted odds ratio: 1.3, 95% confidence interval: 0.97, 1.7; P=0.08. Age, sex, and cirrhosis status were risk factors for IFG/T2D in both populations, while body mass index was positively associated with IFG/T2D in non-Asian but not in Asian participants. No significant differences in sustained virological response rates were seen between patients with normal fasting glucose and patients with IFG/T2D for both populations. These results demonstrate that the prevalence of glucose abnormalities in Asian CHC patients was similar to that in non-Asians, and glucose abnormalities had

  2. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    OpenAIRE

    Park, Weon Wook; Suh, Kuen Tak; Kim, Jeung Il; Ku, Ja Gyung; Lee, Hong Seok; Kim, Seong-Jang; Kim, In-Ju; Kim, Yong-Ki; Lee, Jung Sub

    2008-01-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with ...

  3. Lactate, Glucose and Oxygen Uptake in Human Brain During Recovery from Maximal Exercise

    DEFF Research Database (Denmark)

    Kojiro, I.; Schmalbruch, I.K.; Quistorff, B.

    1999-01-01

    Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake......Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake...

  4. Weight loss after bariatric surgery reverses insulin-induced increases in brain glucose metabolism of the morbidly obese.

    Science.gov (United States)

    Tuulari, Jetro J; Karlsson, Henry K; Hirvonen, Jussi; Hannukainen, Jarna C; Bucci, Marco; Helmiö, Mika; Ovaska, Jari; Soinio, Minna; Salminen, Paulina; Savisto, Nina; Nummenmaa, Lauri; Nuutila, Pirjo

    2013-08-01

    Obesity and insulin resistance are associated with altered brain glucose metabolism. Here, we studied brain glucose metabolism in 22 morbidly obese patients before and 6 months after bariatric surgery. Seven healthy subjects served as control subjects. Brain glucose metabolism was measured twice per imaging session: with and without insulin stimulation (hyperinsulinemic-euglycemic clamp) using [18F]fluorodeoxyglucose scanning. We found that during fasting, brain glucose metabolism was not different between groups. However, the hyperinsulinemic clamp increased brain glucose metabolism in a widespread manner in the obese but not control subjects, and brain glucose metabolism was significantly higher during clamp in obese than in control subjects. After follow-up, 6 months postoperatively, the increase in glucose metabolism was no longer observed, and this attenuation was coupled with improved peripheral insulin sensitivity after weight loss. We conclude that obesity is associated with increased insulin-stimulated glucose metabolism in the brain and that this abnormality can be reversed by bariatric surgery.

  5. Brain Glucose Transporter (Glut3) Haploinsufficiency Does Not Impair Mouse Brain Glucose Uptake

    Science.gov (United States)

    Stuart, Charles A.; Ross, Ian R.; Howell, Mary E. A.; McCurry, Melanie P.; Wood, Thomas G.; Ceci, Jeffrey D.; Kennel, Stephen J.; Wall, Jonathan

    2011-01-01

    Mouse brain expresses three principle glucose transporters. Glut1 is an endothelial marker and is the principal glucose transporter of the blood-brain barrier. Glut3 and Glut6 are expressed in glial cells and neural cells. A mouse line with a null allele for Glut3 has been developed. The Glut3−/− genotype is intrauterine lethal by seven days post-coitis, but the heterozygous (Glut3+/−) littermate survives, exhibiting rapid post-natal weight gain, but no seizures or other behavioral aberrations. At twelve weeks of age, brain uptake of tail vein-injected 3H-2-deoxy glucose in Glut3+/− mice was not different from Glut3+/+ littermates, despite 50% less Glut3 protein expression in the brain. The brain uptake of injected 18F-2-fluoro-2-deoxy glucose was similarly not different from Glut3+/− littermates in the total amount, time course, or brain imaging in the Glut3+/− mice. Glut1 and Glut6 protein expressions evaluated by immunoblots were not affected by the diminished Glut3 expression in the Glut3+/− mice. We conclude that a 50% decrease in Glut3 is not limiting for the uptake of glucose into the mouse brain, since Glut3 haploinsufficiency does not impair brain glucose uptake or utilization. PMID:21316350

  6. Noninvasive skin fluorescence spectroscopy for detection of abnormal glucose tolerance

    Directory of Open Access Journals (Sweden)

    Edward L. Hull, PhD

    2014-09-01

    Full Text Available The ENGINE study evaluated noninvasive skin fluorescence spectroscopy (SFS for detection of abnormal glucose tolerance (AGT. The AGT detection performance of SFS was compared to fasting plasma glucose (FPG and hemoglobin A1C (A1C. The study was a head-to-head comparison of SFS to FPG and A1C in an at-risk population of 507 subjects, with no prior diagnosis of diabetes, each of whom received a 75 g, two-hour oral glucose tolerance test (OGTT. Subjects were measured by SFS on multiple days in fasting and non-fasting states. SFS data were acquired and analyzed with the SCOUT DS® device (VeraLight, Albuquerque, NM, USA. Disease truth was AGT, defined as OGTT ≥ 7.8 mmol/L. Sensitivity, false positive rate (FPR, ROC area, and equal error rate (EER for detection of AGT were computed. The reproducibility of SFS and FPG was assessed. The AGT sensitivity of SFS at the device's recommended screening threshold of 50 was 75.2%, higher than that of FPG (thresholds of 5.6 mmol/L or 6.1 mmol/L and A1C (thresholds of 5.7% or 6.0%. The SFS FPR was 42.1%, comparable to an A1C threshold of 5.7% (FPR = 43.5%. The EERs of SFS, FPG and A1C were similar, as were the partial ROC areas for FPRs of 20–50%. The reproducibility of SFS was 7.7% versus 8.1% for FPG. SFS had similar AGT detection performance to FPG and A1C and is a viable alternative to screening individuals for AGT.

  7. Ketosis proportionately spares glucose utilization in brain.

    Science.gov (United States)

    Zhang, Yifan; Kuang, Youzhi; Xu, Kui; Harris, Donald; Lee, Zhenghong; LaManna, Joseph; Puchowicz, Michelle A

    2013-08-01

    The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate and acetoacetate, as occurs with fasting, starvation, or chronic feeding of a ketogenic diet. The relationship between changes in cerebral metabolic rates of glucose (CMRglc) and degree or duration of ketosis remains uncertain. To investigate if CMRglc decreases with chronic ketosis, 2-[(18)F]fluoro-2-deoxy-D-glucose in combination with positron emission tomography, was applied in anesthetized young adult rats fed 3 weeks of either standard or ketogenic diets. Cerebral metabolic rates of glucose (μmol/min per 100 g) was determined in the cerebral cortex and cerebellum using Gjedde-Patlak analysis. The average CMRglc significantly decreased in the cerebral cortex (23.0±4.9 versus 32.9±4.7) and cerebellum (29.3±8.6 versus 41.2±6.4) with increased plasma ketone bodies in the ketotic rats compared with standard diet group. The reduction of CMRglc in both brain regions correlates linearly by ∼9% for each 1 mmol/L increase of total plasma ketone bodies (0.3 to 6.3 mmol/L). Together with our meta-analysis, these data revealed that the degree and duration of ketosis has a major role in determining the corresponding change in CMRglc with ketosis.

  8. Abnormal glucose metabolism in acute myocardial infarction: influence on left ventricular function and prognosis

    DEFF Research Database (Denmark)

    Høfsten, Dan E; Løgstrup, Brian B; Møller, Jacob E

    2009-01-01

    OBJECTIVES: We studied the influence of abnormal glucose metabolism on left ventricular (LV) function and prognosis in 203 patients with acute myocardial infarction. BACKGROUND: Abnormal glucose metabolism is associated with increased mortality after acute myocardial infarction. This appears to b...... alone did not explain the excess mortality in patients with newly detected or known diabetes....

  9. Cognition and brain abnormalities on MRI in pituitary patients

    International Nuclear Information System (INIS)

    Brummelman, Pauline; Sattler, Margriet G.A.; Meiners, Linda C.; Berg, Gerrit van den; Klauw, Melanie M. van der; Elderson, Martin F.; Dullaart, Robin P.F.; Koerts, Janneke; Werumeus Buning, Jorien; Tucha, Oliver; Wolffenbuttel, Bruce H.R.; Bergh, Alfons C.M. van den; Beek, André P. van

    2015-01-01

    Highlights: • Cognitive impairments are frequently observed in treated NFA patients. • NFA patients with cognitive impairments do not show brain abnormalities on MRI more frequently than patients without cognitive impairments. • The absence of brain abnormalities on brain MRI does not exclude impairments of cognition. - Abstract: Purpose: The extent to which cognitive dysfunction is related to specific brain abnormalities in patients treated for pituitary macroadenoma is unclear. Therefore, we compared brain abnormalities seen on Magnetic Resonance Imaging (MRI) in patients treated for nonfunctioning pituitary macroadenoma (NFA) with or without impairments in cognitive functioning. Methods: In this cross-sectional design, a cohort of 43 NFA patients was studied at the University Medical Center Groningen. White matter lesions (WMLs), cerebral atrophy, (silent) brain infarcts and abnormalities of the temporal lobes and hippocampi were assessed on pre-treatment and post-treatment MRI scans. Post-treatment cognitive examinations were performed using a verbal memory and executive functioning test. We compared our patient cohort with large reference populations representative of the Dutch population. Results: One or more impairments on both cognitive tests were frequently observed in treated NFA patients. No treatment effects were found with regard to the comparison between patients with and without impairments in executive functioning. Interestingly, in patients with one or more impairments on verbal memory function, treatment with radiotherapy had been given more frequently (74% in the impaired group versus 40% in the unimpaired group, P = 0.025). Patients with or without any brain abnormality on MRI did not differ in verbal memory or executive functioning. Conclusions: Brain abnormalities on MRI are not observed more frequently in treated NFA patients with impairments compared to NFA patients without impairments in verbal memory or executive functioning

  10. Cognition and brain abnormalities on MRI in pituitary patients

    Energy Technology Data Exchange (ETDEWEB)

    Brummelman, Pauline [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Sattler, Margriet G.A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen (Netherlands); Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Meiners, Linda C. [Department of Radiology, University of Groningen, University Medical Center Groningen (Netherlands); Berg, Gerrit van den; Klauw, Melanie M. van der [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Elderson, Martin F. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); LifeLines Cohort Study and Biobank, University of Groningen, University Medical Center Groningen (Netherlands); Dullaart, Robin P.F. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Koerts, Janneke [Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen (Netherlands); Werumeus Buning, Jorien, E-mail: j.werumeus.buning@umcg.nl [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Tucha, Oliver [Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen (Netherlands); Wolffenbuttel, Bruce H.R. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); LifeLines Cohort Study and Biobank, University of Groningen, University Medical Center Groningen (Netherlands); Bergh, Alfons C.M. van den [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen (Netherlands); Beek, André P. van, E-mail: a.p.van.beek@umcg.nl [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands)

    2015-02-15

    Highlights: • Cognitive impairments are frequently observed in treated NFA patients. • NFA patients with cognitive impairments do not show brain abnormalities on MRI more frequently than patients without cognitive impairments. • The absence of brain abnormalities on brain MRI does not exclude impairments of cognition. - Abstract: Purpose: The extent to which cognitive dysfunction is related to specific brain abnormalities in patients treated for pituitary macroadenoma is unclear. Therefore, we compared brain abnormalities seen on Magnetic Resonance Imaging (MRI) in patients treated for nonfunctioning pituitary macroadenoma (NFA) with or without impairments in cognitive functioning. Methods: In this cross-sectional design, a cohort of 43 NFA patients was studied at the University Medical Center Groningen. White matter lesions (WMLs), cerebral atrophy, (silent) brain infarcts and abnormalities of the temporal lobes and hippocampi were assessed on pre-treatment and post-treatment MRI scans. Post-treatment cognitive examinations were performed using a verbal memory and executive functioning test. We compared our patient cohort with large reference populations representative of the Dutch population. Results: One or more impairments on both cognitive tests were frequently observed in treated NFA patients. No treatment effects were found with regard to the comparison between patients with and without impairments in executive functioning. Interestingly, in patients with one or more impairments on verbal memory function, treatment with radiotherapy had been given more frequently (74% in the impaired group versus 40% in the unimpaired group, P = 0.025). Patients with or without any brain abnormality on MRI did not differ in verbal memory or executive functioning. Conclusions: Brain abnormalities on MRI are not observed more frequently in treated NFA patients with impairments compared to NFA patients without impairments in verbal memory or executive functioning

  11. Unsuspected glucose abnormalities in patients with coronary artery ...

    African Journals Online (AJOL)

    2006-05-25

    May 25, 2006 ... To compare the ability of fasting glucose, glycosylated haemoglobin (HbA1c), the American. Diabetic Association (ADA) ... All subjects underwent a modified glucose tolerance test whereby fasting and. 2-hour post glucose (75 g) ..... there are no randomised trials demonstrating benefits of early diagnosis.20 ...

  12. Abnormal Glucose Tolerance in Infants and Young Children with Cystic Fibrosis.

    Science.gov (United States)

    Yi, Yaling; Norris, Andrew W; Wang, Kai; Sun, Xingshen; Uc, Aliye; Moran, Antoinette; Engelhardt, John F; Ode, Katie Larson

    2016-10-15

    In cystic fibrosis, abnormal glucose tolerance is associated with decreased lung function and worsened outcomes. Translational evidence indicates that abnormal glucose tolerance may begin in early life. To determine whether very young children with cystic fibrosis have increased abnormal glucose tolerance prevalence compared with control subjects. The secondary objective was to compare area under the curve for glucose and insulin in children with cystic fibrosis with control subjects. This is a prospective multicenter study in children ages 3 months to 5 years with and without cystic fibrosis. Oral glucose tolerance testing with glucose, insulin, and C-peptide was sampled at 0, 10, 30, 60, 90, and 120 minutes. Twenty-three children with cystic fibrosis and nine control subjects had complete data. All control subjects had normal glucose tolerance. Nine of 23 subjects with cystic fibrosis had abnormal glucose tolerance (39%; P = 0.03). Of those, two met criteria for cystic fibrosis-related diabetes, two indeterminate glycemia, and six impaired glucose tolerance. Children with cystic fibrosis failed to exhibit the normal increase in area under the curve insulin with age observed in control subjects (P children with cystic fibrosis. Children with cystic fibrosis lack the normal increase in insulin secretion that occurs in early childhood despite increased glucose. These findings demonstrate that glycemic abnormalities begin very early in cystic fibrosis, possibly because of insufficient insulin secretion.

  13. Brain Glucose Transporter (Glut3) Haploinsufficiency Does Not Impair Mouse Brain Glucose Uptake

    OpenAIRE

    Stuart, Charles A.; Ross, Ian R.; Howell, Mary E. A.; McCurry, Melanie P.; Wood, Thomas G.; Ceci, Jeffrey D.; Kennel, Stephen J.; Wall, Jonathan

    2011-01-01

    Mouse brain expresses three principle glucose transporters. Glut1 is an endothelial marker and is the principal glucose transporter of the blood-brain barrier. Glut3 and Glut6 are expressed in glial cells and neural cells. A mouse line with a null allele for Glut3 has been developed. The Glut3−/− genotype is intrauterine lethal by seven days post-coitis, but the heterozygous (Glut3+/−) littermate survives, exhibiting rapid post-natal weight gain, but no seizures or other behavioral aberration...

  14. Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

    Science.gov (United States)

    Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

    2011-01-01

    OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance. PMID:21270256

  15. Brain areas and pathways in the regulation of glucose metabolism

    NARCIS (Netherlands)

    Diepenbroek, Charlene; Serlie, Mireille J.; Fliers, Eric; Kalsbeek, Andries; la Fleur, Susanne E.

    2013-01-01

    Glucose is the most important source of fuel for the brain and its concentration must be kept within strict boundaries to ensure the organism's optimal fitness. To maintain glucose homeostasis, an optimal balance between glucose uptake and glucose output is required. Besides managing acute changes

  16. Abnormal brain synchrony in Down Syndrome☆

    Science.gov (United States)

    Anderson, Jeffrey S.; Nielsen, Jared A.; Ferguson, Michael A.; Burback, Melissa C.; Cox, Elizabeth T.; Dai, Li; Gerig, Guido; Edgin, Jamie O.; Korenberg, Julie R.

    2013-01-01

    Down Syndrome is the most common genetic cause for intellectual disability, yet the pathophysiology of cognitive impairment in Down Syndrome is unknown. We compared fMRI scans of 15 individuals with Down Syndrome to 14 typically developing control subjects while they viewed 50 min of cartoon video clips. There was widespread increased synchrony between brain regions, with only a small subset of strong, distant connections showing underconnectivity in Down Syndrome. Brain regions showing negative correlations were less anticorrelated and were among the most strongly affected connections in the brain. Increased correlation was observed between all of the distributed brain networks studied, with the strongest internetwork correlation in subjects with the lowest performance IQ. A functional parcellation of the brain showed simplified network structure in Down Syndrome organized by local connectivity. Despite increased interregional synchrony, intersubject correlation to the cartoon stimuli was lower in Down Syndrome, indicating that increased synchrony had a temporal pattern that was not in response to environmental stimuli, but idiosyncratic to each Down Syndrome subject. Short-range, increased synchrony was not observed in a comparison sample of 447 autism vs. 517 control subjects from the Autism Brain Imaging Exchange (ABIDE) collection of resting state fMRI data, and increased internetwork synchrony was only observed between the default mode and attentional networks in autism. These findings suggest immature development of connectivity in Down Syndrome with impaired ability to integrate information from distant brain regions into coherent distributed networks. PMID:24179822

  17. Parameters of glucose metabolism and the aging brain

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild

    2015-01-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean...... age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain...... different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging....

  18. Unsuspected glucose abnormalities in patients with coronary artery ...

    African Journals Online (AJOL)

    HbA1c), the American Diabetic Association (ADA) score and measures of the metabolic syndrome (waist circumference, high-density lipoprotein (HDL), and triglycerides) in predicting an initial diagnosis of diabetes mellitus or abnormal ...

  19. Abnormal scintigrams in demyclinating diseases of the brain

    International Nuclear Information System (INIS)

    Podreka, I.; Heiss, W.D.; Jellinger, K.; Vienna Univ.

    1977-01-01

    In 6 patients with acute or exacerbating demyelinating disease and in 2 cases suffering from adrenoleucodystrophy (Schilder's disease) brain scintigraphy revealed areas with increased isotope uptake. The pathological foci were verified by autopsy in 4 cases and by inspection in 1. These foci are difficult to distinguish from other localized brain diseases causing increased isotope uptake; in addition to the clinical course and to spinal fluid abnormalities reversibility of the scintigraphic lesions indicate demyelinating diseases. The typical pattern of symmetrical lesions within the white matter and the progression of abnormalities from the occipital to the frontal lobe speak in favor of Schilder's disease. (orig.) [de

  20. Influence of abnormal glucose metabolism on coronary microvascular function after a recent myocardial infarction

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Høfsten, Dan E; Christophersen, Thomas B

    2009-01-01

    OBJECTIVES: This study sought to assess the association between abnormal glucose metabolism and abnormal coronary flow reserve (CFR) in patients with a recent acute myocardial infarction (AMI). BACKGROUND: Mortality and morbidity after AMI is high among patients with abnormal glucose metabolism, ...... (140 microg/kg/min) to obtain the hyperemic flow profiles. The CFR was defined as the ratio of hyperemic to baseline peak diastolic coronary flow velocities. RESULTS: Median CFR was 1.9 (interquartile range [IQR] 1.4 to 2.4], and 109 (60%) patients had a CFR...

  1. Morphometric Brain Abnormalities in Boys with Conduct Disorder

    Science.gov (United States)

    Huebner, Thomas; Vloet, Timo D.; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R.; Herpertz, Sabine C.; Herpertz-Dahlmann, Beate

    2008-01-01

    Conduct disorder (CD) is associated with antisocial personality behavior that violates the basic rights of others. Results, on examining the structural brain aberrations in boys' CD, show that boys with CD and cormobid attention-deficit/hyperactivity disorder showed abnormalities in frontolimbic areas that could contribute to antisocial…

  2. Brain glucose content in fetuses of ethanol-fed rats

    Energy Technology Data Exchange (ETDEWEB)

    Pullen, G.; Singh, S.P.; Snyder, A.K.; Hoffen, B.

    1986-03-01

    The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4 and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.

  3. Connectivity and functional profiling of abnormal brain structures in pedophilia.

    Science.gov (United States)

    Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-06-01

    Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. © 2015 Wiley Periodicals, Inc.

  4. Impaired brain energy gain upon a glucose load in obesity.

    Science.gov (United States)

    Wardzinski, Ewelina K; Kistenmacher, Alina; Melchert, Uwe H; Jauch-Chara, Kamila; Oltmanns, Kerstin M

    2018-03-06

    There is evidence that the brain's energy status is lowered in obesity despite of chronic hypercaloric nutrition. The underlying mechanisms are unknown. We hypothesized that the brain of obese people does not appropriately generate energy in response to a hypercaloric supply. Glucose was intravenously infused in 17 normal weights and 13 obese participants until blood glucose concentrations reached the postprandial levels of 7 mmol/L and 10 mmol/L. Changes in cerebral adenosine triphosphate (ATP) and phosphocreatine (PCr) content were measured by 31 phosphorus magnetic resonance spectroscopy and stress hormonal measures regulating glucose homeostasis were monitored. Because vitamin C is crucial for a proper neuronal energy synthesis we determined circulating concentrations during the experimental testing. Cerebral high-energy phosphates were increased at blood glucose levels of 7 mmol/L in normal weights, which was completely missing in the obese. Brain energy content moderately raised only at blood glucose levels of 10 mmol/L in obese participants. Vitamin C concentrations generally correlated with the brain energy content at blood glucose concentrations of 7 mmol/L. Our data demonstrate an inefficient cerebral energy gain upon a glucose load in obese men, which may result from a dysfunctional glucose transport across the blood-brain barrier or a downregulated energy synthesis in mitochondrial oxidation processes. Our finding offers an explanation for the chronic neuroenergetic deficiency and respectively missing satiety perception in obesity. Copyright © 2018. Published by Elsevier Inc.

  5. Hypomelanosis of Ito and brain abnormalities: MRI findings and literature review

    International Nuclear Information System (INIS)

    Steiner, J.; Adamsbaum, C.; Desguerres, I.; Lalande, G.; Raynaud, F.; Ponsot, G.; Kalifa, G.

    1996-01-01

    We report the results of a 14-year retrospective study of brain MRI abnormalities in 12 pediatric patients presenting with hypomelanosis of Ito (HI). Miscellaneous brain abnormalities were found: one patient had a medulloblastoma, three had cortical malformations, and five demonstrated ''minor'' abnormalities such as dilated Virchow-Robin spaces or brain atrophy. We emphasize the polymorphism of brain abnormalities associated with HI. (orig.). With 5 figs., 1 tab

  6. Congenital adrenal hyperplasia and brain magnetic resonance imaging abnormalities.

    Science.gov (United States)

    Samia, Younes-Mhenni; Mahdi, Kamoun; Baha, Zantour; Saida, Jerbi-Ommezine; Tahar, Sfar Mohamed; Habib, Sfar Mohamed

    2010-10-01

    A 15-yr-old male patient with congenital adrenal hyperplasia (CAH) was referred to our department with a one year history of gradual worsening of tremors. He was diagnosed with salt-wasting 21-hydroxylase deficiency CAH at 40 d old and was started on hydrocortisone, fludrocortisone and salt. He was found to have hypertension at 8 yr of age. Detailed investigations failed to detect any cause for secondary hypertension. Physical findings on the current hospitalization objectified obesity, blood pressure of 150/80 mmHg, postural and action tremor, left cerebellar syndrome, reflex tetra pyramidal syndrome and mental decline. Brain magnetic resonance imaging (MRI) showed bilateral periventricular white matter hyperintensity that was more pronounced in the posterior regions and associated with cortico-subcortical atrophy and complete agenesis of the corpus callosum. All investigations for leukoencephalopathy were negative. A diagnosis of brain MRI abnormalities related to CAH was made, and the patient received symptomatic treatment of tremors. Our case report provides evidence of an increased frequency of brain MRI abnormalities in CAH. The literature suggests hormonal imbalance and exposure to excess exogenous glucocorticoids as main probable mechanisms. Thus, in clinical practice, CAH should be considered as one of the possible causes of brain white matter involvement associated with or without cerebral atrophy.

  7. Obstructive sleep apnea is a predictor of abnormal glucose metabolism in chronically sleep deprived obese adults.

    Science.gov (United States)

    Cizza, Giovanni; Piaggi, Paolo; Lucassen, Eliane A; de Jonge, Lilian; Walter, Mary; Mattingly, Megan S; Kalish, Heather; Csako, Gyorgy; Rother, Kristina I

    2013-01-01

    Sleep abnormalities, including obstructive sleep apnea (OSA), have been associated with insulin resistance. To determine the relationship between sleep, including OSA, and glucose parameters in a prospectively assembled cohort of chronically sleep-deprived obese subjects. Cross-sectional evaluation of a prospective cohort study. Tertiary Referral Research Clinical Center. Sleep duration and quality assessed by actigraphy, sleep diaries and questionnaires, OSA determined by a portable device; glucose metabolism assessed by oral glucose tolerance test (oGTT), and HbA1c concentrations in 96 obese individuals reporting sleeping less than 6.5 h on a regular basis. Sixty % of subjects had an abnormal respiratory disturbance index (RDI≥5) and 44% of these subjects had abnormal oGTT results. Severity of OSA as assessed by RDI score was associated with fasting glucose (R = 0.325, p = 0.001) and fasting insulin levels (ρ = 0.217, p = 0.033). Subjects with moderate to severe OSA (RDI>15) had higher glucose concentrations at 120 min than those without OSA (RDIsleep deprived individuals. Since sleep apnea is common and frequently undiagnosed, health care providers should be aware of its occurrence and associated risks. This study was conducted under the NIDDK protocol 06-DK-0036 and is listed in ClinicalTrials.gov NCT00261898.

  8. Blood-Brain Glucose Transfer in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, Michael; Brock, Birgitte; Egefjord, Lærke

    2017-01-01

    There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral...... metabolic rate for glucose (CMRglc) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease. We randomized 38 patients with AD...

  9. Abnormal Brain Network Organization in Body Dysmorphic Disorder

    Science.gov (United States)

    Arienzo, Donatello; Leow, Alex; Brown, Jesse A; Zhan, Liang; GadElkarim, Johnson; Hovav, Sarit; Feusner, Jamie D

    2013-01-01

    Body dysmorphic disorder (BDD) is characterized by preoccupation with misperceived defects of appearance, causing significant distress and disability. Previous studies suggest abnormalities in information processing characterized by greater local relative to global processing. The purpose of this study was to probe whole-brain and regional white matter network organization in BDD, and to relate this to specific metrics of symptomatology. We acquired diffusion-weighted 34-direction MR images from 14 unmedicated participants with DSM-IV BDD and 16 healthy controls, from which we conducted whole-brain deterministic diffusion tensor imaging tractography. We then constructed white matter structural connectivity matrices to derive whole-brain and regional graph theory metrics, which we compared between groups. Within the BDD group, we additionally correlated these metrics with scores on psychometric measures of BDD symptom severity as well as poor insight/delusionality. The BDD group showed higher whole-brain mean clustering coefficient than controls. Global efficiency negatively correlated with BDD symptom severity. The BDD group demonstrated greater edge betweenness centrality for connections between the anterior temporal lobe and the occipital cortex, and between bilateral occipital poles. This represents the first brain network analysis in BDD. Results suggest disturbances in whole brain structural topological organization in BDD, in addition to correlations between clinical symptoms and network organization. There is also evidence of abnormal connectivity between regions involved in lower-order visual processing and higher-order visual and emotional processing, as well as interhemispheric visual information transfer. These findings may relate to disturbances in information processing found in previous studies. PMID:23322186

  10. Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer’s disease: metabolic basis for dementia

    Science.gov (United States)

    Xu, Jingshu; Begley, Paul; Church, Stephanie J.; Patassini, Stefano; McHarg, Selina; Kureishy, Nina; Hollywood, Katherine A.; Waldvogel, Henry J.; Liu, Hong; Zhang, Shaoping; Lin, Wanchang; Herholz, Karl; Turner, Clinton; Synek, Beth J.; Curtis, Maurice A.; Rivers-Auty, Jack; Lawrence, Catherine B.; Kellett, Katherine A. B.; Hooper, Nigel M.; Vardy, Emma R. L. C.; Wu, Donghai; Unwin, Richard D.; Faull, Richard L. M.; Dowsey, Andrew W.; Cooper, Garth J. S.

    2016-01-01

    Impairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer’s disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage. We employed mass spectrometry (MS) to measure metabolites and metals in seven post-mortem brain regions of nine AD patients and nine controls, and plasma-glucose and plasma-copper levels in an ante-mortem case-control study. Glucose, sorbitol and fructose were markedly elevated in all AD brain regions, whereas copper was correspondingly deficient throughout (all P < 0.0001). In the ante-mortem case-control study, by contrast, plasma-glucose and plasma-copper levels did not differ between patients and controls. There were pervasive defects in regulation of glucose and copper in AD brain but no evidence for corresponding systemic abnormalities in plasma. Elevation of brain glucose and deficient brain copper potentially contribute to the pathogenesis of neurodegeneration in AD. PMID:27276998

  11. Comparison of brain perfusion SPECT abnormalities with anatomical imaging in mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Majid Asadi

    2007-02-01

    Full Text Available Background: Trauma is the most common cause of morbidity and mortality in industrialized countries and also in Iran. Anatomical imaging (AI CT and MRI is helpful in the diagnosis of acute traumatic complications however it is not efficient in the diagnosis of disabling injury syndrome. In contrast, brain perfusion SPECT (Single Photon Emission Computed Tomography can be more useful for evaluation of microvascular structure. This study was designed to compare these two diagnostic methods. Methods: A total of 50 patients who had been suffering from traumatic brain injury for more than 1 year, and were followed as mild traumatic brain injury group according to “the Brain Injury Interdisciplinary Special Interest Group of the Ameri can Congress of Rehabilitation Medicine” criteria, were examined by brain perfusion SPECT and AI. The common anatomical classification of the lobes of brain was used. Results: The male to female ratio was 3:2. The mean age was 32.32±11.8 years and mean post-traumatic time was 1.48±0.65 years. The most common symptoms were headache (60%, agusia (36% and anosmia (32%. Among 400 examined brain lobes in this study, brain perfusion SPECT revealed remarkable abnormality in 76 lobes (19%, but AI determined abnormalities in 38 lobes (9.5% therefore, SPECT was twice sensitive than AI in mild traumatic brain injury (P<0.001. The correlation between SPECT and AI findings was 84%. SPECT was more sensitive than AI in demonstrating brain abnormalities in frontal lobe it was more obvious in the male group however, there was no significant difference between more and less than 30 years old groups. Conclusion: According to the findings of this study, we recommend using brain perfusion SPECT for all patients with chronic complications of head trauma, particularly those who have signs and symptoms of hypofrontalism, even though with some abnormalities in AI.

  12. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Qiu eXiangzhe

    2016-05-01

    Full Text Available Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM. However, the DM-related changes in the topological properties in functional brain networks are almost unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs, followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized shortest path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing the functional evidence for the abnormalities of brain networks in DM.

  13. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.

    Science.gov (United States)

    García-Cáceres, Cristina; Quarta, Carmelo; Varela, Luis; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Johansson, Pia; Ninkovic, Jovica; Yi, Chun-Xia; Le Thuc, Ophelia; Szigeti-Buck, Klara; Cai, Weikang; Meyer, Carola W; Pfluger, Paul T; Fernandez, Ana M; Luquet, Serge; Woods, Stephen C; Torres-Alemán, Ignacio; Kahn, C Ronald; Götz, Magdalena; Horvath, Tamas L; Tschöp, Matthias H

    2016-08-11

    We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Obstructive sleep apnea is a predictor of abnormal glucose metabolism in chronically sleep deprived obese adults.

    Directory of Open Access Journals (Sweden)

    Giovanni Cizza

    Full Text Available Sleep abnormalities, including obstructive sleep apnea (OSA, have been associated with insulin resistance.To determine the relationship between sleep, including OSA, and glucose parameters in a prospectively assembled cohort of chronically sleep-deprived obese subjects.Cross-sectional evaluation of a prospective cohort study.Tertiary Referral Research Clinical Center.Sleep duration and quality assessed by actigraphy, sleep diaries and questionnaires, OSA determined by a portable device; glucose metabolism assessed by oral glucose tolerance test (oGTT, and HbA1c concentrations in 96 obese individuals reporting sleeping less than 6.5 h on a regular basis.Sixty % of subjects had an abnormal respiratory disturbance index (RDI≥5 and 44% of these subjects had abnormal oGTT results. Severity of OSA as assessed by RDI score was associated with fasting glucose (R = 0.325, p = 0.001 and fasting insulin levels (ρ = 0.217, p = 0.033. Subjects with moderate to severe OSA (RDI>15 had higher glucose concentrations at 120 min than those without OSA (RDI<5 (p = 0.017. Subjects with OSA also had significantly higher concentrations of plasma ACTH (p = 0.009. Several pro-inflammatory cytokines were higher in subjects with OSA (p<0.050. CRP levels were elevated in this sample, suggesting increased cardiovascular risk.OSA is associated with impaired glucose metabolism in obese, sleep deprived individuals. Since sleep apnea is common and frequently undiagnosed, health care providers should be aware of its occurrence and associated risks.This study was conducted under the NIDDK protocol 06-DK-0036 and is listed in ClinicalTrials.gov NCT00261898.

  15. Relationship between urine pH and abnormal glucose tolerance in a community-based study.

    Science.gov (United States)

    Yoshida, Sakiko; Miyake, Teruki; Yamamoto, Shin; Furukawa, Shinya; Niiya, Tetsuji; Senba, Hidenori; Kanzaki, Sayaka; Yoshida, Osamu; Ishihara, Toru; Koizumi, Mitsuhito; Hirooka, Masashi; Kumagi, Teru; Abe, Masanori; Kitai, Kohichiro; Matsuura, Bunzo; Hiasa, Yoichi

    2017-11-16

    The association between urine pH and abnormal glucose tolerance in men and women is unclear; therefore, we carried out a community-based, cross-sectional study to investigate sex-specific associations between these values, possible indicators of prediabetes and type 2 diabetes. We enrolled 4,945 Japanese individuals (2,490 men and 2,455 women), who had undergone annual health checkups. To investigate the relationship between low urine pH and abnormal glucose tolerance, participants were divided into three groups based on their fasting plasma glucose levels (levels (≤44.3 mmol/mol, 44.3-47.5 mmol/mol and ≥47.5 mmol/mol). To examine the effects of urine pH on abnormal glucose tolerance, participants were categorized into five groups based on their urine pH (5.0, 5.5, 6.0, 6.5 and ≥7.0). Multivariate analysis adjusted for age, body mass index, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, uric acid, creatinine and antidiabetic agent use showed significant associations between low urine pH and both high fasting plasma glucose and high glycated hemoglobin levels (P for trend = 0.0260, 0.0075) in men. Furthermore, after the same adjustments, prevalence rates of abnormal glucose tolerance (≥6.11 mmol/L and ≥6.99 mmol/L), increased significantly as urine pH levels decreased (P for trend = 0.0483, 0.0181) in men. In women, a similar trend was observed without a significant difference. Low urine pH is significantly associated with abnormal glucose tolerance; therefore, measuring urine pH might prove useful for identifying patients at high risk for diabetes. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  16. Structural brain abnormalities in early onset first-episode psychosis

    DEFF Research Database (Denmark)

    Pagsberg, A K; Baaré, W F C; Raabjerg Christensen, A M

    2007-01-01

    BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder......, delusional disorder or other non-organic psychosis), aged 10-18 to those of 29 matched controls, using optimized voxel-based morphometry. RESULTS: Psychotic patients had frontal white matter abnormalities, but expected (regional) gray matter reductions were not observed. Post hoc analyses revealed...... already at illness onset in young schizophrenia spectrum patients, suggests aberrant neurodevelopmental processes in the pathogenesis of these disorders. Gray matter volume changes, however, appear not to be a key feature in early onset first-episode psychosis....

  17. Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne

    2012-01-01

    CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE...... To investigate changes in reward-related brain activations in schizophrenia before and after antipsychotic monotherapy with a dopamine D2/D3 antagonist. DESIGN Longitudinal cohort study. SETTING Psychiatric inpatients and outpatients in the Capital Region of Denmark. PARTICIPANTS Twenty-three antipsychotic...... with the antipsychotic compound amisulpride. Controls were followed up without treatment. MAIN OUTCOME MEASURES Task-related blood oxygen level-dependent activations as measured by functional magnetic resonance imaging before and after antipsychotic treatment. RESULTS At baseline, patients, as compared with controls...

  18. Glucose metabolism, diet composition, and the brain

    NARCIS (Netherlands)

    Diepenbroek, C.

    2017-01-01

    Excessive intake of saturated fat and sugar contributes to both obesity and diabetes development. Since intake of fat and sugar-sweetened beverages exceeds recommended levels worldwide, it is essential to: 1) Understand how fat and sugar intake affect glucose metabolism, and 2) Expand the knowledge

  19. Structural brain abnormalities in early onset first-episode psychosis

    DEFF Research Database (Denmark)

    Pagsberg, A K; Baaré, W F C; Raabjerg Christensen, A M

    2007-01-01

    BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder, delusi...... already at illness onset in young schizophrenia spectrum patients, suggests aberrant neurodevelopmental processes in the pathogenesis of these disorders. Gray matter volume changes, however, appear not to be a key feature in early onset first-episode psychosis.......BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder......, delusional disorder or other non-organic psychosis), aged 10-18 to those of 29 matched controls, using optimized voxel-based morphometry. RESULTS: Psychotic patients had frontal white matter abnormalities, but expected (regional) gray matter reductions were not observed. Post hoc analyses revealed...

  20. [Joint effect of birth weight and obesity measures on abnormal glucose metabolism at adulthood].

    Science.gov (United States)

    Xi, Bo; Cheng, Hong; Chen, Fangfang; Zhao, Xiaoyuan; Mi, Jie

    2016-01-01

    To investigate the joint effect of birth weight and each of obesity measures (body mass index (BMI) and waist circumference (WC)) on abnormal glucose metabolism (including diabetes) at adulthood. Using the historical cohort study design and the convenience sampling method, 1 921 infants who were born in Beijing Union Medical College Hospital from June 1948 to December 1954 were selected to do the follow-up in 1995 and 2001 respectively. Through Beijing Household Registration and Management System, they were invited to participate in this study. A total of 972 subjects (627 were followed up in 1995 and 345 were followed up in 2001) with complete information on genders, age, birth weight, family history of diabetes, BMI, WC, fasting plasma glucose (FPG) and 2-hour plasma glucose (2 h PG) met the study inclusion criteria at the follow-up visits. In the data analysis, they were divided into low, normal, and high birth weight, respectively. The ANOVA and Chi-squared tests were used to compare the differences in their characteristics by birth weight group. In addition, multiple binary Logistic regression model was used to investigate the single effect of birth weight, BMI, and waist circumference on abnormal glucose metabolism at adulthood. Stratification analysis was used to investigate the joint effect of birth weight and each of obesity measures (BMI and WC) on abnormal glucose metabolism. There were 972 subjects (males: 50.7%, mean age: (46.0±2.2) years) included in the final data analysis. The 2 h PG in low birth weight group was (7.6±3.2) mmol/L , which was higher than that in normal birth weight group (6.9±2.1) mmol/L and high birth weight group (6.4±1.3) mmol/L (F=3.88, P=0.021). After adjustment for genders, age, body length, gestation age, family history of diabetes, physical activity, smoking and alcohol consumption, and duration of follow-up, subjects with overweight and obesity at adulthood had 2.73 (95% confidence interval (CI) =2.06- 3.62) times risk

  1. Locating abnormalities in brain blood vessels using parallel computing architecture.

    Science.gov (United States)

    Adeshina, A M; Hashim, R; Khalid, N E A; Abidin, S Z Z

    2012-09-01

    CT and MRI scans are widely used in medical diagnosis procedures, but they only produce 2-D images. However, the human anatomical structure, the abnormalities, tumors, tissues and organs are in 3-D. 2-D images from these devices are difficult to interpret because they only show cross-sectional views of the human structure. Consequently, such circumstances require doctors to use their expert experiences in the interpretation of the possible location, size or shape of the abnormalities, even for large datasets of enormous amount of slices. Previously, the concept of reconstructing 2-D images to 3-D was introduced. However, such reconstruction model requires high performance computation, may either be time-consuming or costly. Furthermore, detecting the internal features of human anatomical structure, such as the imaging of the blood vessels, is still an open topic in the computer-aided diagnosis of disorders and pathologies. This paper proposes a volume visualization framework using Compute Unified Device Architecture (CUDA), augmenting the widely proven ray casting technique in terms of superior qualities of images but with slow speed. Considering the rapid development of technology in the medical community, our framework is implemented on Microsoft.NET environment for easy interoperability with other emerging revolutionary tools. The framework was evaluated with brain datasets from the department of Surgery, University of North Carolina, United States, containing around 109 MRA datasets. Uniquely, at a reasonably cheaper cost, our framework achieves immediate reconstruction and obvious mappings of the internal features of human brain, reliable enough for instantaneous locations of possible blockages in the brain blood vessels.

  2. The Role of Helicobacter pylori Seropositivity in Insulin Sensitivity, Beta Cell Function, and Abnormal Glucose Tolerance

    Directory of Open Access Journals (Sweden)

    Lou Rose Malamug

    2014-01-01

    Full Text Available Infection, for example, Helicobacter pylori (H. pylori, has been thought to play a role in the pathogenesis of type 2 diabetes mellitus (T2DM. Our aim was to determine the role of H. pylori infection in glucose metabolism in an American cohort. We examined data from 4,136 non-Hispanic white (NHW, non-Hispanic black (NHB, and Mexican Americans (MA aged 18 and over from the NHANES 1999-2000 cohort. We calculated the odds ratios for states of glucose tolerance based on the H. pylori status. We calculated and compared homeostatic model assessment insulin resistance (HOMA-IR and beta cell function (HOMA-B in subjects without diabetes based on the H. pylori status. The results were adjusted for age, body mass index (BMI, poverty index, education, alcohol consumption, tobacco use, and physical activity. The H. pylori status was not a risk factor for abnormal glucose tolerance. After adjustment for age and BMI and also adjustment for all covariates, no difference was found in either HOMA-IR or HOMA-B in all ethnic and gender groups except for a marginally significant difference in HOMA-IR in NHB females. H. pylori infection was not a risk factor for abnormal glucose tolerance, nor plays a major role in insulin resistance or beta cell dysfunction.

  3. Effects of MDMA on blood glucose levels and brain glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M. [Hospital General Universitario Gregorio Maranon, Laboratorio de Imagen, Medicina Experimental, Madrid (Spain); Arango, C. [Hospital General Gregorio Maranon, Departamento de Psiquiatria, Madrid (Spain); Ricaurte, G. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States)

    2007-06-15

    This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

  4. Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

    Science.gov (United States)

    Miederer, I; Uebbing, K; Röhrich, J; Maus, S; Bausbacher, N; Krauter, K; Weyer-Elberich, V; Lutz, B; Schreckenberger, M; Urban, R

    2017-05-01

    Δ 9 -Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [ 18 F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of dose: ≤ 0.01 mg/kg) corresponded to an increased glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Neuroanatomical abnormalities in chronic tinnitus in the human brain

    Science.gov (United States)

    Adjamian, Peyman; Hall, Deborah A.; Palmer, Alan R.; Allan, Thomas W.; Langers, Dave R.M.

    2014-01-01

    In this paper, we review studies that have investigated brain morphology in chronic tinnitus in order to better understand the underlying pathophysiology of the disorder. Current consensus is that tinnitus is a disorder involving a distributed network of peripheral and central pathways in the nervous system. However, the precise mechanism remains elusive and it is unclear which structures are involved. Given that brain structure and function are highly related, identification of anatomical differences may shed light upon the mechanism of tinnitus generation and maintenance. We discuss anatomical changes in the auditory cortex, the limbic system, and prefrontal cortex, among others. Specifically, we discuss the gating mechanism of tinnitus and evaluate the evidence in support of the model from studies of brain anatomy. Although individual studies claim significant effects related to tinnitus, outcomes are divergent and even contradictory across studies. Moreover, results are often confounded by the presence of hearing loss. We conclude that, at present, the overall evidence for structural abnormalities specifically related to tinnitus is poor. As this area of research is expanding, we identify some key considerations for research design and propose strategies for future research. PMID:24892904

  6. Clinical features of male patients with alcoholic liver cirrhosis or hepatitis B cirrhosis complicated by abnormal glucose metabolism

    Directory of Open Access Journals (Sweden)

    CHEN Qidan

    2016-02-01

    Full Text Available ObjectiveTo investigate the clinical features of male patients with alcoholic liver cirrhosis (ALC or hepatitis B cirrhosis (HBC complicated by abnormal glucose metabolism. MethodsA total of 287 patients with liver cirrhosis who were admitted to Guangzhou Panyu Central Hospital from January 2008 to September 2013 were selected. Among these patients, 74 had ALC and were all male, including 54 with abnormal glucose metabolism; the other 213 had HBC, including 97 with abnormal glucose metabolism (69 male patients and 28 female patients. A controlled study was performed for the clinical data of ALC and HBC patients with abnormal glucose metabolism, to investigate the association of patients′ clinical manifestations with the indices for laboratory examination, insulin resistance index, incidence rate of abnormal glucose metabolism, and Child-Pugh class. The t-test was applied for comparison of continuous data between groups, the chi-square test was applied for comparison of categorical data between groups, and the Spearman rank correlation was applied for correlation analysis. ResultsCompared with HBC patients, ALC patients had significantly higher incidence rates of abnormal glucose metabolism (730% vs 32.4%, hepatogenous diabetes (35.1% vs 14.6%, fasting hypoglycemia (27.0% vs 10.3%, and impaired glucose tolerance (31.1% vs 14.1% (χ2=4.371, 3.274, 4.784, and 1.633, all P<0.05. The Spearman correlation analysis showed that in ALC and HBC patients, the incidence rate of abnormal glucose metabolism was positively correlated with Child-Pugh class (rs=0.41, P<005. Compared with the HBC patients with abnormal glucose metabolism, the ALC patients with abnormal glucose metabolism had a significantly higher incidence rate of Child-Pugh class A (χ2=7.520, P=0.001, and a significantly lower incidence rate of Child-Pugh class C (χ2=6.542, P=0.003. There were significant differences in the incidence rates of dim complexion, telangiectasia of the

  7. Blood-Brain Glucose Transfer in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, Michael; Brock, Birgitte; Egefjord, Lærke

    2017-01-01

    There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral...

  8. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    Science.gov (United States)

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions. Published by Oxford University Press on behalf of the Guarantors of Brain 2014. This work is written by US Government employees and is in the public domain in the US.

  9. Abnormal Brain Connectivity Spectrum Disorders Following Thimerosal Administration

    Directory of Open Access Journals (Sweden)

    David A. Geier

    2017-03-01

    Full Text Available Background: Autism spectrum disorder (ASD, tic disorder (TD, and hyperkinetic syndrome of childhood (attention deficit disorder [ADD]/attention deficit hyperactivity disorder [ADHD] are disorders recently defined as abnormal connectivity spectrum disorders (ACSDs because they show a similar pattern of abnormal brain connectivity. This study examines whether these disorders are associated with exposure to thimerosal, a mercury (Hg-based preservative. Methods: A hypothesis testing case-control study evaluated the Vaccine Safety Datalink for the potential dose-dependent odds ratios (ORs for diagnoses of ASD, TD, and ADD/ADHD compared to controls, following exposure to Hg from thimerosal-containing Haemophilus influenzae type b vaccines administrated within the first 15 months of life. Febrile seizures, cerebral degeneration, and unspecified disorders of metabolism, which are not biologically plausibly linked to thimerosal, were examined as control outcomes. Results: On a per 25 μg Hg basis, cases diagnosed with ASD (OR = 1.493, TD (OR = 1.428, or ADD/ADHD (OR = 1.503 were significantly (P < .001 more likely than controls to have received increased Hg exposure. Similar relationships were observed when separated by gender. Cases diagnosed with control outcomes were no more likely than controls to have received increased Hg exposure. Conclusion: The results suggest that Hg exposure from thimerosal is significantly associated with the ACSDs of ASD, TD, and ADD/ADHD.

  10. Diabetes and other glucose metabolism abnormalities in Mexican Zapotec and Mixe Indians.

    Science.gov (United States)

    Escobedo, J; Chavira, I; Martínez, L; Velasco, X; Escandón, C; Cabral, J

    2010-04-01

    Aboriginal populations are experiencing an explosive rise in the prevalence of Type 2 diabetes. The purpose of this study was to estimate the prevalence of diabetes and other glucose metabolism abnormalities in Mexican Zapotec and Mixe Indians and to determine their association with known risk factors. A cross-sectional study was conducted in the southern Mexican state of Oaxaca. Two communities of Zapotec population and three of Mixe population were randomly chosen. Mexican Indians>or=35 years old were invited to participate; 394 Zapotec and 730 Mixe Indians participated. Diabetes and other glucose metabolism abnormalities were diagnosed using standard World Health Organization criteria after an oral glucose tolerance test. Prevalence and odds ratio (OR) were estimated with 95% confidence intervals (95% CI). The crude prevalence of diabetes was 8.19% (95% CI 6.7-9.9%) and the age- and sex-adjusted prevalence was 8.27%, significantly higher among Zapotec (8.71%) than among Mixe Indians (6.90%). The prevalence of impaired glucose tolerance was 9.9% and 4.7% of the studied subjects had impaired fasting glucose. The main risk factors related to the occurrence of diabetes were a family history of diabetes (OR 4.1; 95% CI 1.9-8.8), obesity (OR 3.0; 95% CI 1.6-5.6), hypertension (OR 2.6; 95% CI 1.5-4.7) and a high-risk waist-hip ratio (4.6; 95% CI 1.2-17.7). The prevalence of diabetes is high in this population, the highest so far reported in Mexican Indians. Mexico's health system faces a huge challenge to avert the advanced spread of diabetes in this susceptible population.

  11. Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging

    Directory of Open Access Journals (Sweden)

    Nugent Scott

    2016-01-01

    Full Text Available Brain energy metabolism in Alzheimer’s disease (AD is characterized mainly by temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a consequence of the disease, i.e. deteriorating neuronal function leading to lower demand for glucose. This review will address deteriorating glucose metabolism as a problem specific to glucose and one that precedes AD. Hence, ketones and medium chain fatty acids (MCFA could be an alternative source of energy for the aging brain that could compensate for low brain glucose uptake. MCFA in the form of dietary medium chain triglycerides (MCT have a long history in clinical nutrition and are widely regarded as safe by government regulatory agencies. The importance of ketones in meeting the high energy and anabolic requirements of the infant brain suggest they may be able to contribute in the same way in the aging brain. Clinical studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive effects on cognition.

  12. Diabetes and abnormal glucose regulation in the adult population of Burkina Faso: prevalence and predictors.

    Science.gov (United States)

    Millogo, Tieba; Bicaba, Brice W; Soubeiga, Joseph Kouesyandé; Dabiré, Estelle; Médah, Isaie; Kouanda, Séni

    2018-03-13

    The prevalence of diabetes mellitus (DM) is reportedly growing fast in sub-Saharan Africa. There is however a scarcity of epidemiologic data on DM in Burkina Faso. We carried out a secondary analysis of the first survey conducted in Burkina Faso on a nationally representative sample following the World Health Organization (WHO) Stepwise approach to risk factors Surveillance (STEPS) for non-communicable diseases (NCDs) with the aims of identifying the prevalence of NCDs and the prevalence of common risk factors for NCDs. We report here on the prevalence of diabetes and overall abnormal glucose regulation (AGR) and their associated risk factors. In the primary study 4800 individuals were randomly sampled using a stratified multistage clusters sampling process. We used fasting capillary whole blood glucose level to define three glucose regulation statuses using WHO's cut-off levels: normal, diabetes and overall abnormal glucose regulation (impaired fasting glucose and diabetes). Appropriate statistical techniques for the analysis of survey data were used to identify the factors associated with diabetes and abnormal glucose regulation fitting a logistic regression model. Analyses were carried out using Stata Version 14 software. The prevalence of DM and AGR were respectively 5.8% (95% CI: 5-6.7) and 9% (95% CI: 8-10.1). Significant risk factors for DM include age (OR = 1.9; P = 0.009 for the age group of 55-64), obesity (OR: 2.6; P = 0.001), former smoke (OR:2; P = 0.03), second-hand smoke (OR = 1.7; P = 0.006) and total cholesterol level (OR: 2.1; P = 0.024). The same predictors were also found significantly associated with AGR. In addition, having an history family diabetes was protective against AGR (OR = 0.5; P = 0.032). Diabetes is no longer a rare disease in the adult active population of Burkina Faso. Its burden is significant in both rural and urban areas. Health policies that promote healthy life style are needed to give

  13. Facilitated transport of glucose from blood to brain in man and the effect of moderate hypoglycaemia on cerebral glucose utilization

    International Nuclear Information System (INIS)

    Blomqvist, G.; Widen, L.; Hellstrand, E.; Gutniak, M.; Grill, V.

    1991-01-01

    The effect of steady-state moderate hypoglycaemia on human brain homeostasis has been studied with positron emission tomography using D-glucose 11 C(ul) as tracer. To rule out any effects of insulin, the plasma insulin concentration was maintained at the same level under normo- and hypoglycaemic conditions. Reduction of blood glucose by 55% increased the glucose clearance through the blood-brain barrier by 50% and reduced brain glucose consumption by 40%. Blood flow was not affected. The results are consistent with facilitated transport of glucose from blood to brain in humans. The maximal transport rate of glucose from blood to brain was found to be 62±19 (mean±SEM) μmol hg -1 min -1 , and the half-saturation constant was found to be 4.1±3.2 mM. (orig.)

  14. Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints

    Energy Technology Data Exchange (ETDEWEB)

    Picco, Agnese; Ferrara, Michela; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio [University of Genoa and IRCCS San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Largo P. Daneo, 3, 16132, Genoa (Italy); Polidori, M.C. [University of Cologne, Institute of Geriatrics, Cologne (Germany); Cecchetti, Roberta; Baglioni, Mauro; Bastiani, Patrizia; Mecocci, Patrizia [University of Perugia, Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, Perugia (Italy); Morbelli, Silvia; Bossert, Irene [University of Genoa and IRCCS San Martino-IST, Nuclear Medicine, Department of Health Science (DISSAL), Genoa (Italy); Fiorucci, Giuliana; Dottorini, Massimo Eugenio [Nuclear Medicine, S. M. della Misericordia Hospital, Perugia (Italy)

    2014-04-15

    The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain{sup 18}F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities. (orig.)

  15. Structural Brain Abnormalities in Successfully Treated HIV Infection: Associations With Disease and Cerebrospinal Fluid Biomarkers

    NARCIS (Netherlands)

    van Zoest, Rosan A.; Underwood, Jonathan; de Francesco, Davide; Sabin, Caroline A.; Cole, James H.; Wit, Ferdinand W.; Caan, Matthan W. A.; Kootstra, Neeltje A.; Fuchs, Dietmar; Zetterberg, Henrik; Majoie, Charles B. L. M.; Portegies, Peter; Winston, Alan; Sharp, David J.; Gisslén, Magnus; Reiss, Peter; Winston, A.; Prins, M.; Schim van der Loeff, M. F.; Schouten, J.; Schmand, B.; Geurtsen, G. J.; Sharp, D. J.; Villaudy, J.; Berkhout, B.; Gisslén, M.; Pasternak, A.; Sabin, C. A.; Guaraldi, G.; Bürkle, A.; Libert, C.; Franceschi, C.; Kalsbeek, A.; Fliers, E.; Hoeijmakers, J.; Pothof, J.; van der Valk, M.; Bisschop, P. H.; Zaheri, S.; Burger, D.; Cole, J. H.; Zikkenheiner, W.; Janssen, F. R.; Underwood, J.; Kooij, K. W.; Doyle, N.; Verheij, E.; Verboeket, S. O.; Elsenga, B. C.; Hillebregt, M. M. J.; Ruijs, Y. M. C.; Benschop, D. P.; Tembo, L.; McDonald, L.; Stott, M.; Legg, K.; Lovell, A.; Erlwein, O.; Kingsley, C.; Norsworthy, P.; Mullaney, S.; Kruijer, T.; del Grande, L.; Olthof, V.; Visser, G. R.; May, L.; Verbraak, F.; Demirkaya, N.; Visser, I.; Su, T.; Leech, R.; Huguet, J.; Frankin, E.; van der Kuyl, A.; Weijer, K.; Siteur-van Rijnstra, E.; Harskamp-Holwerda, A. M.; Maurer, I.; Mangas Ruiz, M. M.; Girigorie, A. F.; Boeser-Nunnink, B.; de Graaff-Teulen, M.; Dewaele, S.; Garagnani, P.; Pirazzini, C.; Capri, M.; Dall'Olio, F.; Chiricolo, M.; Salvioli, S.; Fuchs, D.; Zetterberg, H.; Weber, D.; Grune, T.; Jansen, E. H. J. M.; de Francesco, D.; Sindlinger, T.; Oehlke, S.

    2018-01-01

    Background. Brain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. Methods. We investigated factors associated with brain

  16. The relationship between sleep and glucagon-like peptide 1 in patients with abnormal glucose tolerance.

    Science.gov (United States)

    Reutrakul, Sirimon; Sumritsopak, Rungtip; Saetung, Sunee; Chanprasertyothin, Suwannee; Anothaisintawee, Thunyarat

    2017-12-01

    Glucagon-like peptide 1 plays a role in glucose regulation. Sleep disturbances (obstructive sleep apnea, insufficient or poor sleep quality) have been shown to adversely affect glucose metabolism. This study aimed to explore the relationship between sleep and glucagon-like peptide 1 regulation in patients with abnormal glucose tolerance. Seventy-one adults with haemoglobin A1c levels between 5.7% and sleep duration and efficiency were obtained from 7-day actigraphy recordings. Obstructive sleep apnea was assessed using an overnight home monitor. Glucagon-like peptide 1 levels were measured during a 75-g glucose tolerance. The area under the curve of glucagon-like peptide 1 was calculated. The mean age (SD) was 55.1 (8.3) years and median (interquartile range) haemoglobin A1c was 5.97% (5.86, 6.23). There was no relationship between sleep duration or efficiency and fasting or area under the curve glucagon-like peptide 1. Glucagon-like peptide 1 levels did not differ among those sleeping ≤ 5.75, > 5.75-sleep apnea severity, correlated with lower area under the curve glucagon-like peptide 1 (B -0.242, P = 0.045), but not with fasting glucagon-like peptide 1 (B -0.213, P = 0.079). After adjusting for sex, haemoglobin A1c and body mass index, increasing apnea-hypopnea index was negatively associated with having area under the curve glucagon-like peptide 1 in the highest quartile (odds ratio 0.581, P = 0.028, 95% CI 0.359, 0.942). This study demonstrated that increasing obstructive sleep apnea severity was associated with lower glucagon-like peptide 1 response to glucose challenge. This could possibly be an additional mechanism by which obstructive sleep apnea affects glucose metabolism. Whether raising glucagon-like peptide 1 levels in patients with abnormal glucose tolerance with more severe obstructive sleep apnea will be beneficial should be explored. © 2017 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European

  17. Sweet taste disorder and vascular complications in patients with abnormal glucose tolerance.

    Science.gov (United States)

    Tsujimoto, Tetsuro; Imai, Kenjiro; Kanda, Sayaka; Kakei, Masafumi; Kajio, Hiroshi; Sugiyama, Takehiro

    2016-10-15

    It remains unknown whether taste disorders can be a risk factor for micro- and macro-vascular diseases in patients with abnormal glucose tolerance. A cross-sectional study in a nationally representative samples of 848 and 849 US adults (aged ≥40years) with diabetes or prediabetes who had sweet and salt taste disorders, respectively, from the National Health and Nutrition Examination Survey 2011-2012. Among the study population, 5.7% had sweet taste disorder and 8.6% had salt taste disorder. These data correspond to approximately 1.5 million and 1.8 million individuals with abnormal glucose tolerance aged 40years or older in the US population, respectively. In the adjusted model, sweet taste disorder was significantly associated with complication of ischemic heart disease (adjusted odds ratio [OR], 2.45; 95% confidence interval [CI], 1.03-5.81; P=0.04). Moreover, sweet taste disorder in patients with diabetes was significantly associated with diabetic retinopathy (adjusted OR, 2.89; 95% CI, 1.09-7.69; P=0.03) and diabetic nephropathy (adjusted OR, 3.17; 95% CI, 1.07-9.36; P=0.03). Meanwhile, salt taste disorder was not significantly associated with diabetic retinopathy, diabetic nephropathy, ischemic heart disease, or stroke. Total sugar intake was significantly higher in patients with sweet taste disorder than in those without it, whereas total daily intake of carbohydrate did not differ significantly. No significant association was observed between salt taste disorder and daily intake of sodium after multivariate analysis. Sweet taste disorder in patients with abnormal glucose tolerance was associated with increased sugar intake and vascular complications. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  18. A glucose fuel cell for implantable brain-machine interfaces.

    Directory of Open Access Journals (Sweden)

    Benjamin I Rapoport

    Full Text Available We have developed an implantable fuel cell that generates power through glucose oxidation, producing 3.4 μW cm(-2 steady-state power and up to 180 μW cm(-2 peak power. The fuel cell is manufactured using a novel approach, employing semiconductor fabrication techniques, and is therefore well suited for manufacture together with integrated circuits on a single silicon wafer. Thus, it can help enable implantable microelectronic systems with long-lifetime power sources that harvest energy from their surrounds. The fuel reactions are mediated by robust, solid state catalysts. Glucose is oxidized at the nanostructured surface of an activated platinum anode. Oxygen is reduced to water at the surface of a self-assembled network of single-walled carbon nanotubes, embedded in a Nafion film that forms the cathode and is exposed to the biological environment. The catalytic electrodes are separated by a Nafion membrane. The availability of fuel cell reactants, oxygen and glucose, only as a mixture in the physiologic environment, has traditionally posed a design challenge: Net current production requires oxidation and reduction to occur separately and selectively at the anode and cathode, respectively, to prevent electrochemical short circuits. Our fuel cell is configured in a half-open geometry that shields the anode while exposing the cathode, resulting in an oxygen gradient that strongly favors oxygen reduction at the cathode. Glucose reaches the shielded anode by diffusing through the nanotube mesh, which does not catalyze glucose oxidation, and the Nafion layers, which are permeable to small neutral and cationic species. We demonstrate computationally that the natural recirculation of cerebrospinal fluid around the human brain theoretically permits glucose energy harvesting at a rate on the order of at least 1 mW with no adverse physiologic effects. Low-power brain-machine interfaces can thus potentially benefit from having their implanted units

  19. Evaluation of glucose metabolic abnormality in postlingually deaf patients using F-18-FDG positron emission tomography and statistical parametric mapping

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Sung; Lee, Dong Soo; Oh, Seung Ha; Kim, Chong Sun; Park, Kwang Suk; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2000-07-01

    We have previously reported the prognostic relevance of cross-modal cortical plasticity in prelingual deaf patients revealed by F-18-FDG PET and SPM analysis. In this study, we investigated metabolic abnormality in postlingual deaf patients, whose clinical features are different from prelingual deafness. Nine postlingual deaf patients (age: 30.5 {+-}14.0) were performed on F-18-FDG brain PET. We compared their PET images with those of age-matched 20 normal controls (age: 27.1 {+-}8.6), and performed correlation analysis to investigate the relationship between glucose metabolism and deaf duration using SPM99. Glucose metabolism of deaf patients was significantly (p<0.05, corrected) decreased in both anterior cingulate, inferior frontal cortices, and superior temporal cortices, and left hippocampus. Metabolism in both superior temporal cortices and association area in inferior parietal cortices showed significant (p<0.01, uncorrected) positive correlation with deaf duration. Decreased metabolism in hippocampus accompanied with hypometabolism in auditory related areas can be explained by recent finding of anatomical connectivity between them, and may be the evidence indicating their functional connectivity. Metabolism recovery in auditory cortex after long deaf duration suggests that cortical plasticity takes place also in postlingual deafness.

  20. Comparative value of thallium and glucose SPECT imaging in childhood brain tumors.

    Science.gov (United States)

    Maria, B L; Drane, W E; Mastin, S T; Jimenez, L A

    1998-11-01

    Thallium-201 chloride (201Tl) single-photon emission computed tomography (SPECT) detects a high percentage of histologically and anatomically diverse pediatric brain tumors. Thallium-201 chloride SPECT and F-18 fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) are the most commonly used radionuclide techniques in neuro-oncology. Having developed a methodology to image 18F-FDG with SPECT, the authors performed SPECT scans coupled with magnetic resonance imaging to assess the comparative sensitivity of 201Tl and 18F-FDG in 19 children with brain tumors. Tumors were detected using 201Tl SPECT in 14 of 19 patients. Five of five postoperative residual tumors were detected by 201Tl SPECT, and six of seven after irradiation recurrences were detected. F-18 fluoro-deoxy-glucose SPECT detected tumors in only three of 19 patients, all of whom had abnormal 201Tl studies (all three after therapy recurrences). Thallium-201 chloride SPECT could be interpreted in 18 of 19 patients without magnetic resonance imaging confirmation, but none of the 19 18F-FDG SPECT studies could be interpreted without magnetic resonance imaging. Thallium-201 chloride SPECT is more sensitive than 18F-FDG SPECT in the detection of primary or recurrent childhood brain tumors. The failure of 18F-FDG SPECT in follow-up after therapy is primarily a problem of limited fluoro-deoxy-glucose uptake, not spatial resolution. Thallium-201 chloride SPECT is a promising imaging modality in neuro-oncology.

  1. Abnormalities in the tricarboxylic acid (TCA) cycle in the brains of schizophrenia patients.

    Science.gov (United States)

    Bubber, P; Hartounian, V; Gibson, G E; Blass, J P

    2011-03-01

    Images of brain metabolism and measurements of activities of components of the electron transport chain support earlier studies that suggest that brain glucose oxidation is inherently abnormal in a significant proportion of persons with schizophrenia. Therefore, we measured the activities of enzymes of the tricarboxylic (TCA) cycle in dorsolateral-prefrontal-cortex from schizophrenia patients (N=13) and non-psychiatric disease controls (N=13): the pyruvate dehydrogenase complex (PDHC), citrate synthase (CS), aconitase, isocitrate dehydrogenase (ICDH), the alpha-ketoglutarate dehydrogenase complex (KGDHC), succinate thiokinase (STH), succinate dehydrogenase (SDH), fumarase and malate dehydrogenase (MDH). Activities of aconitase (18.4%, pTCA cycle, were lower, but SDH (18.3%, pTCA cycle and cognitive function, age or choline acetyl transferase activity, except for aconitase activity which decreased slightly with age (r=0.55, p=003). The increased activities of dehydrogenases in the second half of the TCA cycle may reflect a compensatory response to reduced activities of enzymes in the first half. Such alterations in the components of TCA cycle are adequate to alter the rate of brain metabolism. These results are consistent with the imaging studies of hypometabolism in schizophrenia. They suggest that deficiencies in mitochondrial enzymes can be associated with mental disease that takes the form of schizophrenia. Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.

  2. Physical activity, fitness, glucose homeostasis, and brain morphology in twins.

    Science.gov (United States)

    Rottensteiner, Mirva; Leskinen, Tuija; Niskanen, Eini; Aaltonen, Sari; Mutikainen, Sara; Wikgren, Jan; Heikkilä, Kauko; Kovanen, Vuokko; Kainulainen, Heikki; Kaprio, Jaakko; Tarkka, Ina M; Kujala, Urho M

    2015-03-01

    The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity. From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses. According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

  3. Glucagon-like peptide-1 (GLP-1) raises blood-brain glucose transfer capacity and hexokinase activity in human brain

    DEFF Research Database (Denmark)

    Gejl, Michael; Lerche, Susanne; Egefjord, Lærke

    2013-01-01

    In hyperglycemia, glucagon-like peptide-1 (GLP-1) lowers brain glucose concentration together with increased net blood-brain clearance and brain metabolism, but it is not known whether this effect depends on the prevailing plasma glucose (PG) concentration. In hypoglycemia, glucose depletion...... potentially impairs brain function. Here, we test the hypothesis that GLP-1 exacerbates the effect of hypoglycemia. To test the hypothesis, we determined glucose transport and consumption rates in seven healthy men in a randomized, double-blinded placebo-controlled cross-over experimental design. The acute...... effect of GLP-1 on glucose transfer in the brain was measured by positron emission tomography (PET) during a hypoglycemic clamp (3 mM plasma glucose) with (18)F-fluoro-2-deoxy-glucose (FDG) as tracer of glucose. In addition, we jointly analyzed cerebrometabolic effects of GLP-1 from the present...

  4. Effect of glucose level on brain FDG-PET images

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Young; Lee, Yong Ki; Ahn, Sung Min [Dept. of Radiological Science, Gachon University, Seongnam (Korea, Republic of)

    2017-06-15

    In addition to tumors, normal tissues, such as the brain and myocardium can intake {sup 18}F-FDG, and the amount of {sup 18}F-FDG intake by normal tissues can be altered by the surrounding environment. Therefore, a process is necessary during which the contrasts of the tumor and normal tissues can be enhanced. Thus, this study examines the effects of glucose levels on FDG PET images of brain tissues, which features high glucose activity at all times, in small animals. Micro PET scan was performed on fourteen mice after injecting {sup 18}F-FDG. The images were compared in relation to fasting. The findings showed that the mean SUV value w as 0 .84 higher in fasted mice than in non-fasted mice. During observation, the images from non-fasted mice showed high accumulation in organs other than the brain with increased surrounding noise. In addition, compared to the non-fasted mice, the fasted mice showed higher early intake and curve increase. The findings of this study suggest that fasting is important in assessing brain functions in brain PET using {sup 18}F-FDG. Additional studies to investigate whether caffeine levels and other preprocessing items have an impact on the acquired images would contribute to reducing radiation exposure in patients.

  5. Mapping abnormal subcortical brain morphometry in an elderly HIV+ cohort

    Directory of Open Access Journals (Sweden)

    Benjamin S.C. Wade

    2015-01-01

    Full Text Available Over 50% of HIV+ individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV+ participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD and radial distances (RD defined on each region's surfaces. We also investigated effects of nadir CD4+ T-cell counts, viral load, time since diagnosis (TSD and cognition on subcortical morphology. Lastly, we explored whether HIV+ participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF model. The model was validated with 2-fold cross-validation. Volumes of HIV+ participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV+ people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV+ participants vs. controls, our RF model attained an area under the curve of 72%.

  6. Abnormal brain activation in excoriation (skin-picking) disorder

    DEFF Research Database (Denmark)

    Odlaug, Brian L.; Hampshire, Adam; Chamberlain, Samuel R

    2016-01-01

    encompassing bilateral dorsal striatum (maximal in right caudate), bilateral anterior cingulate and right medial frontal regions. These abnormalities were, for the most part, outside the dorsal planning network typically activated by executive planning tasks. Conclusions: Abnormalities of neural regions...

  7. D-[U-11C]glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects

    International Nuclear Information System (INIS)

    Gutniak, M.; Blomqvist, G.; Widen, L.; Stone-Elander, S.; Hamberger, B.; Grill, V.

    1990-01-01

    We used D-[U-11C]glucose to evaluate transport and metabolism of glucose in the brain in eight nondiabetic and six insulin-dependent diabetes mellitus (IDDM) subjects. IDDM subjects were treated by continuous subcutaneous insulin infusion. Blood glucose was regulated by a Biostator-controlled glucose infusion during a constant insulin infusion. D-[U-11C]-glucose was injected for positron emission tomography studies during normoglycemia as well as during moderate hypoglycemia [arterial plasma glucose 2.74 +/- 0.14 in nondiabetic and 2.80 +/- 0.26 mmol/l (means +/- SE) in IDDM subjects]. Levels of free insulin were constant and similar in both groups. The tracer data were analyzed using a three-compartment model with a fixed correction for 11CO2 egression. During normoglycemia the influx rate constant (k1) and blood-brain glucose flux did not differ between the two groups. During hypoglycemia k1 increased significantly and similarly in both groups (from 0.061 +/- 0.007 to 0.090 +/- 0.006 in nondiabetic and from 0.061 +/- 0.006 to 0.093 +/- 0.013 ml.g-1.min-1 in IDDM subjects). During normoglycemia the tracer-calculated metabolism of glucose was higher in the whole brain in the nondiabetic than in the diabetic subjects (22.0 +/- 1.9 vs. 15.6 +/- 1.1 mumol.100 g-1.min-1, P less than 0.01). During hypoglycemia tracer-calculated metabolism was decreased by 40% in nondiabetic subjects and by 28% in diabetic subjects. The results indicate that uptake of glucose is normal, but some aspect of glucose metabolism is abnormal in a group of well-controlled IDDM subjects

  8. Reversal of brain metabolic abnormalities following treatment of AIDS dementia complex with 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine): a PET-FDG study

    International Nuclear Information System (INIS)

    Brunetti, A.; Berg, G.; Di Chiro, G.

    1989-01-01

    Brain glucose metabolism was evaluated in four patients with acquired immunodeficiency syndrome (AIDS) dementia complex using [ 18 F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) scans at the beginning of therapy with 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine), and later in the course of therapy. In two patients, baseline, large focal cortical abnormalities of glucose utilization were reversed during the course of therapy. In the other two patients, the initial PET study did not reveal pronounced focal alterations, while the post-treatment scans showed markedly increased cortical glucose metabolism. The improved cortical glucose utilization was accompanied in all patients by immunologic and neurologic improvement. PET-FDG studies can detect cortical metabolic abnormalities associated with AIDS dementia complex, and may be used to monitor the metabolic improvement in response to AZT treatment

  9. Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Murrin L Charles

    2011-03-01

    Full Text Available Abstract Background Methamphetamine (METH, an addictive psycho-stimulant drug with euphoric effect is known to cause neurotoxicity due to oxidative stress, dopamine accumulation and glial cell activation. Here we hypothesized that METH-induced interference of glucose uptake and transport at the endothelium can disrupt the energy requirement of the blood-brain barrier (BBB function and integrity. We undertake this study because there is no report of METH effects on glucose uptake and transport across the blood-brain barrier (BBB to date. Results In this study, we demonstrate that METH-induced disruption of glucose uptake by endothelium lead to BBB dysfunction. Our data indicate that a low concentration of METH (20 μM increased the expression of glucose transporter protein-1 (GLUT1 in primary human brain endothelial cell (hBEC, main component of BBB without affecting the glucose uptake. A high concentration of 200 μM of METH decreased both the glucose uptake and GLUT1 protein levels in hBEC culture. Transcription process appeared to regulate the changes in METH-induced GLUT1 expression. METH-induced decrease in GLUT1 protein level was associated with reduction in BBB tight junction protein occludin and zonula occludens-1. Functional assessment of the trans-endothelial electrical resistance of the cell monolayers and permeability of dye tracers in animal model validated the pharmacokinetics and molecular findings that inhibition of glucose uptake by GLUT1 inhibitor cytochalasin B (CB aggravated the METH-induced disruption of the BBB integrity. Application of acetyl-L-carnitine suppressed the effects of METH on glucose uptake and BBB function. Conclusion Our findings suggest that impairment of GLUT1 at the brain endothelium by METH may contribute to energy-associated disruption of tight junction assembly and loss of BBB integrity.

  10. Control of Hepatic Glucose Metabolism by Islet and Brain

    Science.gov (United States)

    Rojas, Jennifer M.; Schwartz, Michael W.

    2014-01-01

    Dysregulation of hepatic glucose uptake (HGU) and inability of insulin to suppress hepatic glucose production (HGP), both contribute to hyperglycemia in patients with type 2 diabetes (T2D). Growing evidence suggests that insulin can inhibit HGP not only through a direct effect on the liver, but also via a mechanism involving the brain. Yet the notion that insulin action in the brain plays a physiological role in the control of HGP continues to be controversial. Although studies in dogs suggest that the direct hepatic effect of insulin is sufficient to explain day-to-day control of HGP, a surprising outcome has been revealed by recent studies in mice investigating whether the direct hepatic action of insulin is necessary for normal HGP: when hepatic insulin signaling pathway was genetically disrupted, HGP was maintained normally even in the absence of direct input from insulin. Here we present evidence that points to a potentially important role of the brain in the physiological control of both HGU and HGP in response to input from insulin as well as other hormones and nutrients. PMID:25200294

  11. Metabolism of glucose in brain of patients with Parkinson's disease

    International Nuclear Information System (INIS)

    Yokoi, Fuji; Ando, Kazuya; Iio, Masaaki.

    1984-01-01

    We examined 11 C accumulation by positron emission computed tomography in the region of interest (ROI) in the brain of 8 patients with Parkinson's disease and 5 normal controls when administered with 11 C-glucose (per os). 11 C-glucose was prepared from 11 CO 2 by photosynthesis. 1) No significant difference was observed in the 11 C accumulation in the striatum and cerebral cortex (frontal cortex, temporal cortex and occipital cortex) in 4 patients with Parkinson's disease between continuous medication and 7--10 day interruption of medication. 2) No difference was observed in the 11 C accumulation in the striatum and cerebral cortex between 8 patients with Parkinson's disease and 5 normal controls. (author)

  12. Effects of hyperbaric treatment in cerebral air embolism on intracranial pressure, brain oxygenation, and brain glucose metabolism in the pig

    NARCIS (Netherlands)

    van Hulst, Robert A.; Drenthen, Judith; Haitsma, Jack J.; Lameris, Thomas W.; Visser, Gerhard H.; Klein, Jan; Lachmann, Burkhard

    2005-01-01

    OBJECTIVE: To evaluate the effects of hyperbaric oxygen treatment after cerebral air embolism on intracranial pressure, brain oxygenation, brain glucose/lactate metabolism, and electroencephalograph. DESIGN: Prospective animal study. SETTING: Hyperbaric chamber. SUBJECTS: Eleven Landrace/Yorkshire

  13. Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans

    Science.gov (United States)

    Objective: In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during carbohydrate ingestion suggest that glucose may regulate HT signaling but are potentially confoun...

  14. SPECT brain perfusion abnormalities in mild or moderate traumatic brain injury.

    Science.gov (United States)

    Abdel-Dayem, H M; Abu-Judeh, H; Kumar, M; Atay, S; Naddaf, S; El-Zeftawy, H; Luo, J Q

    1998-05-01

    The purpose of this atlas is to present a review of the literature showing the advantages of SPECT brain perfusion imaging (BPI) in mild or moderate traumatic brain injury (TBI) over other morphologic imaging modalities such as x-ray CT or MRI. The authors also present the technical recommendations for SPECT brain perfusion currently practiced at their center. For the radiopharmaceutical of choice, a comparison between early and delayed images using Tc-99m HMPAO and Tc-99m ECD showed that Tc-99m HMPAO is more stable in the brain with no washout over time. Therefore, the authors feel that Tc-99m HMPAO is preferable to Tc-99m ECD. Recommendations regarding standardizing intravenous injection, the acquisition, processing parameters, and interpretation of scans using a ten grade color scale, and use of the cerebellum as the reference organ are presented. SPECT images of 228 patients (age range, 11 to 88; mean, 40.8 years) with mild or moderate TBI and no significant medical history that interfered with the results of the SPECT BP were reviewed. The etiology of the trauma was in the following order of frequency: motor vehicle accidents (45%) followed by blow to the head (36%) and a fall (19%). Frequency of the symptoms was headache (60.9%), memory problems (27.6%), dizziness (26.7%), and sleep disorders (8.7%). Comparison between patients imaged early (3 months) from the time of the accident, showed that early imaging detected more lesions (4.2 abnormal lesions per study compared to 2.7 in those imaged more than 3 months after the accident). Of 41 patients who had mild traumatic injury without loss of consciousness and had normal CT, 28 studies were abnormal. Focal areas of hypoperfusion were seen in 77% (176 patients, 612 lesions) of the group of 228 patients. The sites of abnormalities were in the following order: basal ganglia and thalami, 55.2%, frontal lobes, 23.8%, temporal lobes, 13%, parietal, 3.7%, insular and occipital lobes together, 4.6%.

  15. Incidental sinus abnormalities in 256 patients referred for brain MRI

    Directory of Open Access Journals (Sweden)

    Ghanaati H

    2007-06-01

    Full Text Available Background: Imaging abnormalities in the paranasal sinuses are regularly noted as incidental findings on MRI, however, little is known about their prevalence in the Iranian population. The purpose of this study was to classify these findings in the paranasal sinuses as seen on MRI and to investigate the prevalence, according to site and type of paranasal abnormality. Methods: In this cross-sectional study, the T2-weighted axial MRI of 256 patients with diseases unrelated to their paranasal sinuses were reviewed between May 2002 and June 2003. The findings were categorized according to the anatomic location and the imaging characteristics of the abnormality. The abnormalities recorded included total sinus opacification, mucoperiosteal thickening >5mm, air fluid levels and retention cysts or polyps. Unilateral or bilateral involvement and septal deviation were also noted. A sinus was considered normal if it was fully aerated and no soft-tissue density was apparent within the cavity. Results: Among our cases, 111 (43.5% were male and 145 (56.5% were female. Of these patients, abnormalities in one or more of the sinus groups were found in 110 subjects (42.9%, 55.5% of which were male and 44.5% were female (P=0.001. Maxillary sinus abnormalities were observed in 66.4% of the patients, while ethmoid sinus abnormalities were found in 63.6%. Of the ethmoid abnormalities, 21% were found in the anterior section, 9% in the middle ethmoid, and 8% in the posterior ethmoid. The most common abnormality found was mucosal thickening. Among our cases, 23.4% had septal deviation, which was significantly higher among those with sinusitis (29% versus 19.1%; P<0.01. Of those patients with sinus involvement, 16% were involved in the sphenoid sinus and 5% in the frontal sinus. The results obtained from the patients with sinus abnormality revealed that 85% suffered from cough, nasal obstruction, runny nose, facial pain and post nasal discharge and 24% had been diagnosed

  16. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives

    Science.gov (United States)

    Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O.

    2014-01-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and 18F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic rates including hyperactivity in globus pallidus indicative of basal ganglia involvement. Changes in basal ganglia metabolism offer potential insight into targeting strategies for therapeutic deep brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives

  17. Persistent Abnormal Coronary Flow Reserve in Association with Abnormal Glucose Metabolism Affects Prognosis in Acute Myocardial Infarction

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Høfsten, Dan E; Christophersen, Thomas B

    2011-01-01

    Objectives: To evaluate changes in coronary flow reserve (CFR) over time after acute myocardial infarction (AMI) in relation to left ventricular (LV) function and glucometabolic state and prognostic implication of abnormal CFR. Methods: 154 patients with first time AMI had a comprehensive...... assessment of the LV function and CFR at baseline and after 3 months of follow-up. CFR was measured noninvasively in left descending artery by transthoracic echocardiography. Results: Eighty-five patients had an abnormal CFR at baseline. At baseline patients with persistently normal CFR had higher wall...... motion score index (WMI), ejection fraction (EF) and S' compared with patients with abnormal CFR. At follow-up patients with persistently normal CFR had higher WMI, EF, S' and lower end-systolic diameter compared with patients with abnormal microcirculation. Performing univariate logistical regression...

  18. Structural brain abnormalities in early onset first-episode psychosis

    DEFF Research Database (Denmark)

    Pagsberg, A K; Baaré, William Frans Christian; Raabjerg Christensen, A M

    2007-01-01

    BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder...

  19. Brain perfusion studies in the evaluation of acute neurologic abnormalities.

    Science.gov (United States)

    Zuckier, Lionel S; Sogbein, O O

    2013-03-01

    Two categories of single-photon radiopharmaceuticals for brain perfusion exist, nonlipophilic and lipophilic compounds. The former are useful in performing simple flow examinations which today have application primarily in the determination of brain death. The latter also exhibit a parenchymal uptake phase that allows for evaluation of the distribution of blood flow within the brain. The lipophilic radiopharmaceuticals, therefore, have application in the evaluation of patients following catastrophic brain injury and traumatic brain injury (TBI) and in prognosticating the outcome following cerebral vascular accidents. Use of these agents to monitor therapy with thrombolytic agents, although theoretically helpful, is technically difficult due to the need to institute treatment rapidly, without undue delay. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Diabetes, Abnormal Glucose, Dyslipidemia, Hypertension, and Risk of Inflammatory and Other Breast Cancer.

    Science.gov (United States)

    Schairer, Catherine; Gadalla, Shahinaz M; Pfeiffer, Ruth M; Moore, Steven C; Engels, Eric A

    2017-06-01

    Background: Obesity has been associated with substantially higher risk of inflammatory breast cancer (IBC) than other breast cancer. Here, we assess whether comorbidities of obesity, namely diabetes, abnormal glucose, dyslipidemia, and hypertension, are differentially related to risk of IBC and other breast cancers by tumor stage at diagnosis (localized/regional/distant/unstaged). Methods: We used linked SEER-Medicare data, with female breast cancer cases ages 66+ years identified by SEER registries (years 1992-2011). We divided first breast cancers into IBC ( N = 2,306), locally advanced non-IBC (LABC; N = 10,347), and other ( N = 197,276). We selected female controls ( N = 200,000) from a stratified 5% random sample of Medicare recipients alive and breast cancer free. We assessed exposures until 12 months before diagnosis/selection using Medicare claims data. We estimated odds ratios (OR) and 99.9% confidence intervals (CI) using unconditional logistic regression. Results: Diabetes was associated with increased risk of distant IBC (98.5% of IBC cases; OR 1.44; 99.9% CI 1.21-1.71), distant (OR 1.24; 99.9% CI, 1.09-1.40) and regional (OR 1.29 (99.9% CI, 1.14-1.45) LABC, and distant (OR 1.23; 99.9% CI, 1.10-1.39) and unstaged (OR 1.32; 99.9% CI, 1.18-1.47) other breast cancers. Dyslipidemia was associated with reduced risk of IBC (OR 0.80; 95% CI, 0.67-0.94) and other breast cancers except localized disease. Results were similar by tumor estrogen receptor status. Abnormal glucose levels and hypertension had little association with risk of any tumor type. Conclusions: Associations with diabetes and dyslipidemia were similar for distant stage IBC and other advanced tumors. Impact: If confirmed, such findings could suggest avenues for prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 862-8. ©2017 AACR . ©2017 American Association for Cancer Research.

  1. Magnetic resonance imaging of neonatal brain. Assessment of normal and abnormal findings

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Koh; Kadono, Naoko; Kawase, Shohji; Kihara, Minako; Matsuo, Yasutaka; Yoshioka, Hiroshi; Kinugasa, Akihiko; Sawada, Tadashi (Kyoto Prefectural Univ. of Medicine (Japan))

    1994-11-01

    To establish the normal MRI appearance of the neonatal brain, magnetic resonance imaging (MRI) was performed on 124 neonates who admitted to our neonatal intensive care unit. Degree of myelination, ventricular size, width of the extracerebral space and focal lesion in the brain were evaluated to investigate the relationship between MRI findings of neonatal brain and the neurological prognosis. 85 neonates underwent MRI both at neonatal period and at the corrected age of one year. The change of abnormal MRI findings was evaluated. 19 neonates had abnormal neurological outcome on subsequent examinations. Delayed myelination, ventriculomegaly and large extracerebral space were seen in 13, 7 and 9 neonates respectively. 4, 3 and 5 neonates out of them showed abnormal neurological prognosis respectively. Of the 19 neonates with focal lesion in MRI, 2 had parenchymal hematoma in the brain, 2 had subdural hematoma, 5 had chronic hematoma following subependymal hemorrhage, 6 had cystic formation following subependymal hemorrhage, 2 had subcortical leukomalacia, one had periventricular leukomalacia and one had cyst in the parenchyma of cerebellum. 4 neonates of 19 with focal lesion in MRI showed abnormal development. Of the neonates who had abnormal neurological prognosis, 7 neonates showed no abnormal finding in MRI at neonatal period. 3 of them had mild mental retardation. MRI shows promise in the neonatal period. It facilitates recognition of abnormalities of neonatal brain and may be used to predict abnormal neurologic outcome. However physiological change in the brain of neonates, especially of premature neonates, should be considered on interpreting these findings. Awareness of developmental features should help to minimize misinterpretation of normal changes in the neonatal brain. (author).

  2. Magnetic resonance imaging of neonatal brain. Assessment of normal and abnormal findings

    International Nuclear Information System (INIS)

    Hasegawa, Koh; Kadono, Naoko; Kawase, Shohji; Kihara, Minako; Matsuo, Yasutaka; Yoshioka, Hiroshi; Kinugasa, Akihiko; Sawada, Tadashi

    1994-01-01

    To establish the normal MRI appearance of the neonatal brain, magnetic resonance imaging (MRI) was performed on 124 neonates who admitted to our neonatal intensive care unit. Degree of myelination, ventricular size, width of the extracerebral space and focal lesion in the brain were evaluated to investigate the relationship between MRI findings of neonatal brain and the neurological prognosis. 85 neonates underwent MRI both at neonatal period and at the corrected age of one year. The change of abnormal MRI findings was evaluated. 19 neonates had abnormal neurological outcome on subsequent examinations. Delayed myelination, ventriculomegaly and large extracerebral space were seen in 13, 7 and 9 neonates respectively. 4, 3 and 5 neonates out of them showed abnormal neurological prognosis respectively. Of the 19 neonates with focal lesion in MRI, 2 had parenchymal hematoma in the brain, 2 had subdural hematoma, 5 had chronic hematoma following subependymal hemorrhage, 6 had cystic formation following subependymal hemorrhage, 2 had subcortical leukomalacia, one had periventricular leukomalacia and one had cyst in the parenchyma of cerebellum. 4 neonates of 19 with focal lesion in MRI showed abnormal development. Of the neonates who had abnormal neurological prognosis, 7 neonates showed no abnormal finding in MRI at neonatal period. 3 of them had mild mental retardation. MRI shows promise in the neonatal period. It facilitates recognition of abnormalities of neonatal brain and may be used to predict abnormal neurologic outcome. However physiological change in the brain of neonates, especially of premature neonates, should be considered on interpreting these findings. Awareness of developmental features should help to minimize misinterpretation of normal changes in the neonatal brain. (author)

  3. Effects of Intensive Statin Therapy on Left Ventricular Function in Patients with Myocardial Infarction and Abnormal Glucose Tolerance

    DEFF Research Database (Denmark)

    Auscher, Søren; Løgstrup, Brian Bridal; Møller, Jacob Eifer

    2017-01-01

    statin therapy. Patients were assessed with an oral glucose tolerance test and their left ventricular (LV) function was assessed with speckle-tracking echocardiography measuring regional longitudinal systolic strain (RLSS) in the infarct area. RESULTS: Overall RLSS in the infarct area improved by a mean...... (±SD) of -4.22% (±5.19) in the intensive-care group and -2.48% (±4.01) in the usual-care group after 1 month (p = 0.047). In patients with abnormal glucose tolerance, RLSS improved by -5.01% (±5.28) in the intensive-care group and -2.15% (±4.22) in the usual-care group (p = 0.01). CONCLUSIONS: Early...... high-dose statin treatment improved RLSS in the infarct area in patients with AMI, and a trend of greater improvement was seen in patients with abnormal glucose tolerance....

  4. Abnormal transient rise in hepatic glucose production after oral glucose in non-insulin-dependent diabetic subjects.

    Science.gov (United States)

    Thorburn, A; Litchfield, A; Fabris, S; Proietto, J

    1995-05-01

    A transient rise in hepatic glucose production (HGP) after an oral glucosa load has been reported in some insulin-resistant states such as in obese fa/fa Zucker rats. The aim of this study was to determine whether this rise in HGP also occurs in subjects with established non-insulin-dependent diabetes mellitus (NIDDM). Glucose kinetics were measured basally and during a double-label oral glucose tolerance test (OGTT) in 12 NIDDM subjects and 12 non-diabetic 'control' subjects. Twenty minutes after the glucose load, HGP had increased 73% above basal in the NIDDM subjects (7.29 +/- 0.52 to 12.58 +/- 1.86 mumol/kg/min, P < 0.02). A transient rise in glucagon (12 pg/ml above basal, P < 0.004) occurred at a similar time. In contrast, the control subjects showed no rise in HGP or plasma glucagon. HGP began to suppress 40-50 min after the OGTT in both the NIDDM and control subjects. A 27% increase in the rate of gut-derived glucose absorption was also observed in the NIDDM group, which could be the result of increased gut glucose absorption or decreased first pass extraction of glucose by the liver. Therefore, in agreement with data in animal models of NIDDM, a transient rise in HGP partly contributes to the hyperglycemia observed after an oral glucose load in NIDDM subjects.

  5. Internalized racism, body fat distribution, and abnormal fasting glucose among African-Caribbean women in Dominica, West Indies.

    Science.gov (United States)

    Butler, Cleve; Tull, Eugene S; Chambers, Earle C; Taylor, Jerome

    2002-03-01

    The current study examined the relationship of internalized racism to glucose intolerance in a population of Afro-Caribbean women aged 18 to 55. Also of interest was whether this relationship would be differentially influenced by the type of body fat distribution or confounded by the level of hostility. A total of 244 women were selected from a systematic sample of households on the island of Dominica, West Indies. Demographic data together with information on internalized racism were collected by questionnaire. Anthropometric information and fasting blood glucose were also measured. Women with high levels of internalized racism exhibited an increased risk of elevated fasting glucose compared to those with low levels of internalized racism (odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.1-5.5). There was no difference in mean body mass index (BMI) by level of internalized racism. However those with high internalized racism had a significantly larger waist circumference after adjusting for age, education, hostility, and elevated fasting glucose status. In multivariate analyses controlling for age, education, hostility, and either weight or BMI, internalized racism remained independently associated with elevated fasting glucose. However, once waist circumference was included in the model, the relationship of internalized racism to elevated fasting glucose was not statistically significant. This study demonstrates a significant relationship between internalized racism and abnormal levels of fasting glucose which may be mediated through abdominal fat. The exact nature of the relationship of internalized racism to glucose intolerance may be an important area of future study.

  6. Abnormal brain iron homeostasis in human and animal prion disorders.

    Directory of Open Access Journals (Sweden)

    Ajay Singh

    2009-03-01

    Full Text Available Neurotoxicity in all prion disorders is believed to result from the accumulation of PrP-scrapie (PrP(Sc, a beta-sheet rich isoform of a normal cell-surface glycoprotein, the prion protein (PrP(C. Limited reports suggest imbalance of brain iron homeostasis as a significant associated cause of neurotoxicity in prion-infected cell and mouse models. However, systematic studies on the generality of this phenomenon and the underlying mechanism(s leading to iron dyshomeostasis in diseased brains are lacking. In this report, we demonstrate that prion disease-affected human, hamster, and mouse brains show increased total and redox-active Fe (II iron, and a paradoxical increase in major iron uptake proteins transferrin (Tf and transferrin receptor (TfR at the end stage of disease. Furthermore, examination of scrapie-inoculated hamster brains at different timepoints following infection shows increased levels of Tf with time, suggesting increasing iron deficiency with disease progression. Sporadic Creutzfeldt-Jakob disease (sCJD-affected human brains show a similar increase in total iron and a direct correlation between PrP and Tf levels, implicating PrP(Sc as the underlying cause of iron deficiency. Increased binding of Tf to the cerebellar Purkinje cell neurons of sCJD brains further indicates upregulation of TfR and a phenotype of neuronal iron deficiency in diseased brains despite increased iron levels. The likely cause of this phenotype is sequestration of iron in brain ferritin that becomes detergent-insoluble in PrP(Sc-infected cell lines and sCJD brain homogenates. These results suggest that sequestration of iron in PrP(Sc-ferritin complexes induces a state of iron bio-insufficiency in prion disease-affected brains, resulting in increased uptake and a state of iron dyshomeostasis. An additional unexpected observation is the resistance of Tf to digestion by proteinase-K, providing a reliable marker for iron levels in postmortem human brains. These

  7. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism

    Science.gov (United States)

    Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

    2016-01-01

    Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism. PMID:26964832

  8. Neuroendocrine Abnormalities in Patients with Traumatic Brain Injury

    Science.gov (United States)

    1991-01-01

    oxytocin (41). However. global brain damage may not substantially increase ACTH secretion. Our study in rats showed that fluid percussion brain injury...who were comatose following trauma. Plasma cortisol and aldosterone levels wcre measured at 4-h intervals throughout three consecutive 24-h cycles in...148). In dog and rabbit, hypothalamic compressive lesion led to a hypothyroidisr within 4 weeks (30). The relationship between responses to head

  9. Cellular distribution of glucose and monocarboxylate transporters in human brain white matter and multiple sclerosis lesions

    NARCIS (Netherlands)

    Nijland, P.G.; Michailidou, I.; Witte, M.E.; Mizee, M.R.; van der Pol, SM; Hof, B.; Reijerkerk, A.; Pellerin, L.; van der Valk, P.; de Vries, H.E.; van Horssen, J.

    2014-01-01

    To ensure efficient energy supply to the high demanding brain, nutrients are transported into brain cells via specific glucose (GLUT) and monocarboxylate transporters (MCT). Mitochondrial dysfunction and altered glucose metabolism are thought to play an important role in the progression of

  10. Use of a Connected Glucose Meter and Certified Diabetes Educator Coaching to Decrease the Likelihood of Abnormal Blood Glucose Excursions: The Livongo for Diabetes Program.

    Science.gov (United States)

    Downing, Janelle; Bollyky, Jenna; Schneider, Jennifer

    2017-07-11

    The Livongo for Diabetes Program offers members (1) a cellular technology-enabled, two-way messaging device that measures blood glucose (BG), centrally stores the glucose data, and delivers messages back to the individual in real time; (2) unlimited BG test strips; and (3) access to a diabetes coaching team for questions, goal setting, and automated support for abnormal glucose excursions. The program is sponsored by at-risk self-insured employers, health plans and provider organizations where it is free to members with diabetes or it is available directly to the person with diabetes where they cover the cost. The objective of our study was to evaluate BG data from 4544 individuals with diabetes who were enrolled in the Livongo program from October 2014 through December 2015. Members used the Livongo glucose meter to measure their BG levels an average of 1.8 times per day. We estimated the probability of having a day with a BG reading outside of the normal range (70-180 mg/dL, or 3.9-10.0 mmol/L) in months 2 to 12 compared with month 1 of the program, using individual fixed effects to control for individual characteristics. Livongo members experienced an average 18.4% decrease in the likelihood of having a day with hypoglycemia (BG 180 mg/dL) in months 2-12 compared with month 1 as the baseline. The biggest impact was seen on hyperglycemia for nonusers of insulin. We do not know all of the contributing factors such as medication or other treatment changes during the study period. These findings suggest that access to a connected glucose meter and certified diabetes educator coaching is associated with a decrease in the likelihood of abnormal glucose excursions, which can lead to diabetes-related health care savings. ©Janelle Downing, Jenna Bollyky, Jennifer Schneider. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 11.07.2017.

  11. Brain Structure Abnormalities in Adolescent Girls with Conduct Disorder

    Science.gov (United States)

    Fairchild, Graeme; Hagan, Cindy C.; Walsh, Nicholas D.; Passamonti, Luca; Calder, Andrew J.; Goodyer, Ian M.

    2013-01-01

    Background: Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD.…

  12. Thrombotic thrombocytopenic purpura: MR demonstration of reversible brain abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    D' Aprile, P.; Carella, A.; Pagliarulo, R. (Univ. of Bari (Italy)); Farchi, G. (Oncology Institute, Bari (Italy))

    1994-01-01

    We report a case of thrombotic thrombocytopenic purpura evaluated by MR, Multiple hyperintense foci on the TS-weighted images, observed principally in the brain stem and in the region of the basal nuclei, and neurologic signs disappeared after 15 days of therapy. 6 refs., 2 figs.

  13. An unusual presentation of muscle-eye-brain disease: severe eye abnormalities with mild muscle and brain involvement.

    Science.gov (United States)

    Demir, Ercan; Gucuyener, Kivilcim; Akturk, Aysima; Talim, Beril; Konus, Oznur; Del Bo, Roberto; Ghezzi, Serena; Comi, Giacomo P

    2009-10-01

    Muscle-eye-brain disease (MEB) is characterised by congenital muscular dystrophy, structural brain malformations and eye abnormalities. We report a MEB case whose presenting sign was congenital blindness. She was investigated primarily for eye abnormalities at onset. She had bilateral retinal detachment and microphthalmia. Mild axial hypotonia and motor retardation were attributed to cerebral disorder in another center. Muscle biopsy showed mild myopathic changes and significant alpha-dystroglycan deficiency. Analysis of the POMGnT1 showed a novel homozygous mutation 1814G>C, causing p.Arg605Pro change. This case expands the clinical spectrum of MEB with unusually severe eye abnormalities compared to mild skeletal muscle and brain involvement.

  14. Abnormal release of incretins and cortisol after oral glucose in subjects with insulin-resistant myotonic dystrophy

    DEFF Research Database (Denmark)

    Johansson, Asa; Olsson, Tommy; Cederquist, Kristina

    2002-01-01

    OBJECTIVE: Although the incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), as well as glucagon and cortisol, are known to influence islet function, the role of these hormones in conditions of insulin resistance and development of type 2 diabetes is unknown...... response. Furthermore, cortisol and ACTH levels increased paradoxically in patients after glucose; this was more pronounced in patients with long CTG repeat expansions. CONCLUSIONS: This study showed that the GLP-1 and ACTH/cortisol responses to oral glucose are abnormal in insulin-resistant DM1 patients...

  15. Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism.

    Science.gov (United States)

    Wartchow, Krista Minéia; Tramontina, Ana Carolina; de Souza, Daniela F; Biasibetti, Regina; Bobermin, Larissa D; Gonçalves, Carlos-Alberto

    2016-06-01

    Brain metabolism is highly dependent on glucose, which is derived from the blood circulation and metabolized by the astrocytes and other neural cells via several pathways. Glucose uptake in the brain does not involve insulin-dependent glucose transporters; however, this hormone affects the glucose influx to the brain. Changes in cerebrospinal fluid levels of S100B (an astrocyte-derived protein) have been associated with alterations in glucose metabolism; however, there is no evidence whether insulin modulates glucose metabolism and S100B secretion. Herein, we investigated the effect of S100B on glucose metabolism, measuring D-(3)H-glucose incorporation in two preparations, C6 glioma cells and acute hippocampal slices, and we also investigated the effect of insulin on S100B secretion. Our results showed that: (a) S100B at physiological levels decreases glucose uptake, through the multiligand receptor RAGE and mitogen-activated protein kinase/ERK signaling, and (b) insulin stimulated S100B secretion via PI3K signaling. Our findings indicate the existence of insulin-S100B modulation of glucose utilization in the brain tissue, and may improve our understanding of glucose metabolism in several conditions such as ketosis, streptozotocin-induced dementia and pharmacological exposure to antipsychotics, situations that lead to changes in insulin signaling and extracellular levels of S100B.

  16. Gray Matter Concentration Abnormality in Brains of Narcolepsy Patients

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Eun Yeon; Tae, Woo Suk; Kim, Sung Tae; Hong, Seung Bong [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2009-12-15

    To investigate gray matter concentration changes in the brains of narcoleptic patients. Twenty-nine narcoleptic patient with cataplexy and 29 age and sex-matched normal subjects (mean age, 31 years old) underwent volumetric MRIs. The MRIs were spatially normalized to a standard T1 template and subdivided into gray matter, white matter, and cerebrospinal fluid (CSF). These segmented images were then smoothed using a 12-mm full width at half maximum (FWHM) isotropic Gaussian kernel. An optimized voxel-based morphometry protocol was used to analyze brain tissue concentrations using SPM2 (statistical parametric mapping). A one-way analysis of variance was applied to the concentration analysis of gray matter images. Narcoleptics with cataplexy showed reduced gray matter concentration in bilateral thalami, left gyrus rectus, bilateral frontopolar gyri, bilateral short insular gyri, bilateral superior frontal gyri, and right superior temporal and left inferior temporal gyri compared to normal subjects (uncorrected p < 0.001). Furthermore, small volume correction revealed gray matter concentration reduction in bilateral nuclei accumbens, hypothalami, and thalami (false discovery rate corrected p < 0.05). Gray matter concentration reductions were observed in brain regions related to excessive daytime sleepiness, cognition, attention, and memory in narcoleptics with cataplexy

  17. Neonatal brain abnormalities and memory and learning outcomes at 7 years in children born very preterm.

    Science.gov (United States)

    Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

    2014-01-01

    Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term-born controls. Neonatal brain abnormalities, and in particular deep grey-matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function.

  18. Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Cianfoni, A., E-mail: acianfoni@hotmail.com [Neuroradiology, Neurocenter of Italian Switzerland–Ospedale regionale Lugano, Via Tesserete 46, Lugano, 6900, CH (Switzerland); Caulo, M., E-mail: caulo@unich.it [Department of Neuroscience and Imaging, University of Chieti, Via dei Vestini 33, 6610 Chieti. Italy (Italy); Cerase, A., E-mail: alfonsocerase@gmail.com [Unit of Neuroimaging and Neurointervention NINT, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, Policlinico “Santa Maria alle Scotte”, V.le Bracci 16, Siena (Italy); Della Marca, G., E-mail: dellamarca@rm.unicatt.it [Neurology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Falcone, C., E-mail: carlo_falc@libero.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Di Lella, G.M., E-mail: gdilella@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Gaudino, S., E-mail: sgaudino@sirm.org [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Edwards, J., E-mail: edwardjc@musc.edu [Neuroscience Dept., Medical University of South Carolina, 96J Lucas st, 29425, Charleston, SC (United States); Colosimo, C., E-mail: colosimo@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy)

    2013-11-01

    Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.

  19. Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM

    International Nuclear Information System (INIS)

    Mitrakou, A.; Kelley, D.; Veneman, T.; Jenssen, T.; Pangburn, T.; Reilly, J.; Gerich, J.

    1990-01-01

    To assess the role of muscle and liver in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM), we administered an oral glucose load enriched with [14C]glucose to 10 NIDDM subjects and 10 age- and weight-matched nondiabetic volunteers and compared muscle glucose disposal by measuring forearm balance of glucose, lactate, alanine, O2, and CO2. In addition, we used the dual-lable isotope method to compare overall rates of glucose appearance (Ra) and disappearance (Rd), suppression of endogenous glucose output, and splanchnic glucose sequestration. During the initial 1-1.5 h after glucose ingestion, plasma glucose increased by approximately 8 mM in NIDDM vs. approximately 3 mM in nondiabetic subjects (P less than 0.01); overall glucose Ra was nearly 11 g greater in NIDDM than nondiabetic subjects, but glucose Rd was not significantly different in NIDDM and nondiabetic subjects. The greater overall glucose Ra of NIDDM subjects was due to 6.8 g greater endogenous glucose output (13.7 +/- 1.1 vs. 6.8 +/- 1.0 g, P less than 0.01) and 3.8 g less oral glucose splanchnic sequestration of the oral load (31.4 +/- 1.5 vs. 27.5 +/- 0.9 g, P less than 0.05). Although glucose taken up by muscle was not significantly different in NIDDM and nondiabetic subjects (39.3 +/- 3.5 vs. 41.0 +/- 2.5 g/5 h), a greater amount of the glucose taken up by muscle in NIDDM was released as lactate and alanine (11.7 +/- 1.0 vs. 5.2 +/- 0.3 g in nondiabetic subjects, P less than 0.01), and less was stored (11.7 +/- 1.3 vs. 16.9 +/- 1.5 g, P less than 0.05). We conclude that increased systemic glucose delivery, due primarily to reduced suppression of endogenous hepatic glucose output and, to a lesser extent, reduced splanchnic glucose sequestration, is the predominant factor responsible for postprandial hyperglycemia in NIDDM

  20. Brain perfusion abnormality in patients with chronic pain.

    Science.gov (United States)

    Honda, Tetsumi; Maruta, Toshihiko; Takahashi, Kumiko

    2007-06-01

    We performed single photon emission computed tomography (SPECT) of the brain in 15 patients with chronic pain (males, 7; females, 8; average age 49.1 +/- 17.9 years) and identified the locus of cerebral blood flow reduction by a new analytical method (easy Z-score Imaging System: eZIS) to clarify the functional neuroanatomical basis of chronic pain. Of the 15 patients, 6 had backache, 2 neck pain, 2 gonalgia, and 5 pain at other sites, with an average Visual analog scale of pain (VAS) value of 6.1 +/- 1.9. In comparison with a information on a data base on physically unimpaired persons, the dorsolateral prefrontal area (both sides, right dominant), medial prefrontal area (both sides), dorsal aspect of the anterior cingulate gyrus nociceptive cortex (both sides) and the lateral part of the orbitofrontal cortex (right side) were found to have blood flow reduction in the group of patients with chronic pain. As for chronic pain and its correlation with clinical features such as a depressive state, anticipation anxiety, PTSD, and conversion hysteria, the mechanism in the brain that was suggested by this study should be followed-up by functional neuroimaging studies.

  1. Abnormal brain structure in youth who commit homicide.

    Science.gov (United States)

    Cope, L M; Ermer, E; Gaudet, L M; Steele, V R; Eckhardt, A L; Arbabshirani, M R; Caldwell, M F; Calhoun, V D; Kiehl, K A

    2014-01-01

    Violence that leads to homicide results in an extreme financial and emotional burden on society. Juveniles who commit homicide are often tried in adult court and typically spend the majority of their lives in prison. Despite the enormous costs associated with homicidal behavior, there have been no serious neuroscientific studies examining youth who commit homicide. Here we use neuroimaging and voxel-based morphometry to examine brain gray matter in incarcerated male adolescents who committed homicide (n = 20) compared with incarcerated offenders who did not commit homicide (n = 135). Two additional control groups were used to understand further the nature of gray matter differences: incarcerated offenders who did not commit homicide matched on important demographic and psychometric variables (n = 20) and healthy participants from the community (n = 21). Compared with incarcerated adolescents who did not commit homicide (n = 135), incarcerated homicide offenders had reduced gray matter volumes in the medial and lateral temporal lobes, including the hippocampus and posterior insula. Feature selection and support vector machine learning classified offenders into the homicide and non-homicide groups with 81% overall accuracy. Our results indicate that brain structural differences may help identify those at the highest risk for committing serious violent offenses.

  2. Brain perfusion abnormality in patients with chronic pain

    International Nuclear Information System (INIS)

    Honda, Tetsumi; Maruta, Toshihiko; Takahashi, Kumiko

    2007-01-01

    We performed single photon emission computed tomography (SPECT) of the brain in 15 patients with chronic pain (males, 7; females, 8; average age 49.1±17.9 years) and identified the locus of cerebral blood flow reduction by a new analytical method (easy Z-score Imaging System: eZIS) to clarify the functional neuroanatomical basis of chronic pain. Of the 15 patients, 6 had backache, 2 neck pain, 2 gonalgia, and 5 pain at other sites, with an average Visual analog scale of pain (VAS) value of 6.1±1.9. In comparison with a information on a data base on physically unimpaired persons, the dorsolateral prefrontal area (both sides, right dominant), medial prefrontal area (both sides), dorsal aspect of the anterior cingulate gyrus nociceptive cortex (both sides) and the lateral part of the orbitofrontal cortex (right side) were found to have blood flow reduction in the group of patients with chronic pain. As for chronic pain and its correlation with clinical features such as a depressive state, anticipation anxiety, post-traumatic stress disorder (PTSD), and conversion hysteria, the mechanism in the brain that was suggested by this study should be followed-up by functional neuroimaging studies. (author)

  3. Glucagon-like peptide-1 inhibits blood-brain glucose transfer in humans

    DEFF Research Database (Denmark)

    Lerche, Susanne; Brock, Birgitte; Rungby, Jørgen

    2008-01-01

    OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has many effects on glucose homeostasis, and GLP-1 receptors are broadly represented in many tissues including the brain. Recent research in rodents suggests a protective effect of GLP-1 on brain tissue. The mechanism is unknown. We therefore tested...... whether these neuroprotective effects could relate to changes of glucose transport and consumption. RESEARCH DESIGN AND METHODS: We studied 10 healthy men in a randomized, double-blinded, placebo-controlled cross-over experiment. We used positron emission tomography to determine the acute insulin......-independent effect of GLP-1 on unidirectional glucose transport into the brain during a pituitary-pancreatic normoglycemic (plasma glucose approximately 4.5 mmol/l) clamp with 18-fluoro-deoxy-glucose as tracer. RESULTS: On average, GLP-1 reduced cerebral glucose transport by 27% in total cerebral gray matter (P = 0...

  4. Regional brain glucose use in unstressed rats after two days of starvation

    International Nuclear Information System (INIS)

    Mans, A.M.; Davis, D.W.; Hawkins, R.A.

    1987-01-01

    Regional brain glucose use was measured in conscious, unrestrained, fed rats and after 2 days of starvation, using quantitative autoradiography and [6- 14 C]glucose. Plasma glucose, lactate, and ketone body concentrations and brain glucose and lactate content were measured in separate groups of rats. Glucose concentrations were lower in starved rats in both plasma and brain; plasma ketone body concentrations were elevated. Glucose use was found to be lower throughout the brain by about 12%. While some areas seemed to be affected more than others, statistical analysis showed that none were exceptionally different. The results could not be explained by increased loss of 14 C as lactate or pyruvate during the experimental period, because the arteriovenous differences of these species were insignificant. The calculated contribution by ketone bodies to the total energy consumption was between 3 and 9% for the brain as a whole in the starved rats and could, therefore, partially account for the depression seen in glucose use. It was concluded that glucose oxidation is slightly depressed throughout the brain after 2 days of starvation

  5. Abnormality of cerebral cortical glucose metabolism in temporal lobe epilepsy with cognitive function impairment

    International Nuclear Information System (INIS)

    Bang-Hung Yang; Tsung-Szu Yeh; Tung-Ping Su; Jyh-Cheng Chen; Ren-Shyan Liu

    2004-01-01

    Objective: People with epilepsy commonly report having problems with their memory. Many indicate that memory difficulties significantly hinder their functioning at work, in school, and at home. Besides, some studies have reported that memory performance as a prognostic factor is of most value in patients with risk of refractory epilepsy and when used in a multidisciplinary setting. However, the cerebral cortical areas involving memory impairment in epilepsy is still unknown. The purpose of this study was to access changes of cerebral glucose metabolism of epilepsy patients using [F-18] fluorodeoxyglucose positron emission tomography (FDG PET). Method: Nine temporal lobe epilepsy patients were studied. Each patient was confirmed with lesions in right mesial temporal lobe by MRI, PET and EEG. Serial cognition function tests were performed. Regional cerebral glucose metabolism (rCMRglc) was measured by PET at 45 minutes after injection of 370 MBq of FDG. Parametric images were generated by grand mean scaling each scan to 50. The images were then transformed into standard stereotactic space. Statistical parametric mapping (SPM2) was applied to find the correlations between verbal memory, figure memory, perception intelligent quotation (PIQ) and rCMRglc in epilepsy patients. The changes of rCMRglc were significant if corrected p value was less than 0.05. Results: There was no significant relationship between figure memory score and verbal memory score. FDG-PET scan showed changes of rCMRglc positive related with verbal memory score in precentral gyms of right frontal lobe (Brodmann area 4, corrected p < 0.001, voxel size 240) and cingulated gyms of right limbic lobe (Brodmann area 32, corrected p=0.002, voxel size 143). No negative relationship was demonstrable between verbal memory and rCMRglc in this study. Besides, significanfiy positive correlation between figure memory was shown in cuneus of right occipital lobe (Brodmann area 18, corrected p < 0.001, voxel size

  6. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability

    NARCIS (Netherlands)

    García-Cáceres, Cristina; Quarta, Carmelo; Varela, Luis; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Johansson, Pia; Ninkovic, Jovica; Yi, Chun-Xia; Le Thuc, Ophelia; Szigeti-Buck, Klara; Cai, Weikang; Meyer, Carola W.; Pfluger, Paul T.; Fernandez, Ana M.; Luquet, Serge; Woods, Stephen C.; Torres-Alemán, Ignacio; Kahn, C. Ronald; Götz, Magdalena; Horvath, Tamas L.; Tschöp, Matthias H.

    2016-01-01

    We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and

  7. Neurobehavioral Abnormalities Associated with Executive Dysfunction after Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Rodger Ll. Wood

    2017-10-01

    Full Text Available Objective: This article will address how anomalies of executive function after traumatic brain injury (TBI can translate into altered social behavior that has an impact on a person’s capacity to live safely and independently in the community.Method: Review of literature on executive and neurobehavioral function linked to cognitive ageing in neurologically healthy populations and late neurocognitive effects of serious TBI. Information was collated from internet searches involving MEDLINE, PubMed, PyscINFO and Google Scholar as well as the authors’ own catalogs.Conclusions: The conventional distinction between cognitive and emotional-behavioral sequelae of TBI is shown to be superficial in the light of increasing evidence that executive skills are critical for integrating and appraising environmental events in terms of cognitive, emotional and social significance. This is undertaken through multiple fronto-subcortical pathways within which it is possible to identify a predominantly dorsolateral network that subserves executive control of attention and cognition (so-called cold executive processes and orbito-frontal/ventro-medial pathways that underpin the hot executive skills that drive much of behavior in daily life. TBI frequently involves disruption to both sets of executive functions but research is increasingly demonstrating the role of hot executive deficits underpinning a wide range of neurobehavioral disorders that compromise relationships, functional independence and mental capacity in daily life.

  8. Statistical distribution of blood serotonin as a predictor of early autistic brain abnormalities

    Directory of Open Access Journals (Sweden)

    Janušonis Skirmantas

    2005-07-01

    Full Text Available Abstract Background A wide range of abnormalities has been reported in autistic brains, but these abnormalities may be the result of an earlier underlying developmental alteration that may no longer be evident by the time autism is diagnosed. The most consistent biological finding in autistic individuals has been their statistically elevated levels of 5-hydroxytryptamine (5-HT, serotonin in blood platelets (platelet hyperserotonemia. The early developmental alteration of the autistic brain and the autistic platelet hyperserotonemia may be caused by the same biological factor expressed in the brain and outside the brain, respectively. Unlike the brain, blood platelets are short-lived and continue to be produced throughout the life span, suggesting that this factor may continue to operate outside the brain years after the brain is formed. The statistical distributions of the platelet 5-HT levels in normal and autistic groups have characteristic features and may contain information about the nature of this yet unidentified factor. Results The identity of this factor was studied by using a novel, quantitative approach that was applied to published distributions of the platelet 5-HT levels in normal and autistic groups. It was shown that the published data are consistent with the hypothesis that a factor that interferes with brain development in autism may also regulate the release of 5-HT from gut enterochromaffin cells. Numerical analysis revealed that this factor may be non-functional in autistic individuals. Conclusion At least some biological factors, the abnormal function of which leads to the development of the autistic brain, may regulate the release of 5-HT from the gut years after birth. If the present model is correct, it will allow future efforts to be focused on a limited number of gene candidates, some of which have not been suspected to be involved in autism (such as the 5-HT4 receptor gene based on currently available clinical and

  9. Association between dopamine D4 receptor polymorphism and age related changes in brain glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    Full Text Available Aging is associated with reductions in brain glucose metabolism in some cortical and subcortical regions, but the rate of decrease varies significantly between individuals, likely reflecting genetic and environmental factors and their interactions. Here we test the hypothesis that the variant of the dopamine receptor D4 (DRD4 gene (VNTR in exon 3, which has been associated with novelty seeking and sensitivity to environmental stimuli (negative and positive including the beneficial effects of physical activity on longevity, influence the effects of aging on the human brain. We used positron emission tomography (PET and [(18F]fluoro-D-glucose ((18FDG to measure brain glucose metabolism (marker of brain function under baseline conditions (no stimulation in 82 healthy individuals (age range 22-55 years. We determined their DRD4 genotype and found an interaction with age: individuals who did not carry the 7-repeat allele (7R-, n = 53 had a significant (p<0.0001 negative association between age and relative glucose metabolism (normalized to whole brain glucose metabolism in frontal (r = -0.52, temporal (r = -0.51 and striatal regions (r = -0.47, p<0.001; such that older individuals had lower metabolism than younger ones. In contrast, for carriers of the 7R allele (7R+ n = 29, these correlations with age were not significant and they only showed a positive association with cerebellar glucose metabolism (r = +0.55; p = 0.002. Regression slopes of regional brain glucose metabolism with age differed significantly between the 7R+ and 7R- groups in cerebellum, inferior temporal cortex and striatum. These results provide evidence that the DRD4 genotype might modulate the associations between regional brain glucose metabolism and age and that the carriers of the 7R allele appear to be less sensitive to the effects of age on brain glucose metabolism.

  10. Brain glucose utilization in systemic lupus erythematosus with neuropsychiatric symptoms: a controlled positron emission tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Otte, A. [Institute of Nuclear Medicine, University Hospital, Basel (Switzerland)]|[Department of Nuclear Medicine, University Hospital Freiburg (Germany); Weiner, S.M. [Department of Rheumatology and Immunology, University Hospital Freiburg (Germany); Peter, H.H. [Department of Rheumatology and Immunology, University Hospital Freiburg (Germany); Mueller-Brand, J. [Institute of Nuclear Medicine, University Hospital, Basel (Switzerland); Goetze, M. [Institute of Nuclear Medicine, University Hospital, Basel (Switzerland); Moser, E. [Department of Nuclear Medicine, University Hospital Freiburg (Germany); Gutfleisch, J. [Department of Rheumatology and Immunology, University Hospital Freiburg (Germany); Hoegerle, S. [Department of Nuclear Medicine, University Hospital Freiburg (Germany); Juengling, F.D. [Department of Nuclear Medicine, University Hospital Freiburg (Germany); Nitzsche, E.U. [Department of Nuclear Medicine, University Hospital Freiburg (Germany)

    1997-07-01

    In contrast to morphological imaging [such as magnetic resonance imaging (MRI) or computed tomography], functional imaging may be of advantage in the detection of brain abnormalities in cases of neuropsychiatric systemic lupus erythematosus (SLE). Therefore, we studied 13 patients (aged 40{+-}14 years, 11 female, 2 male) with neuropsychiatric SLE who met four of the American Rheumatism Association criteria for the classification of SLE. Ten clinically and neurologically healthy volunteers served as controls (aged 40{+-}12 years, 5 female, 5 male). Both groups were investigated using fluorine-18-labelled fluorodeoxyglucose brain positron emission tomography (PET) and cranial MRI. The normal controls and 11 of the 13 patients showed normal MRI scans. However, PET scan was abnormal in all 13 SLE patients. Significant group-to-group differences in the glucose metabolic index (GMI=region of interest uptake/global uptake at the level of the basal ganglia and thalamus) were found in the parieto-occipital region on both sides: the GMI of the parieto-occipital region on the right side was 0.922{+-}0.045 in patients and 1.066{+-}0.081 in controls (P<0.0001, Mann Whitney U test), while on the left side it was 0.892{+-}0.060 in patients and 1.034{+-}0.051 in controls (P=0.0002). Parieto-occipital hypometabolism is a conspicuous finding in mainly MRI-negative neuropsychiatric SLE. As the parieto-occipital region is located at the boundary of blood supply of all three major arteries, it could be the most vulnerable zone of the cerebrum and may be affected at an early stage of the cerebrovascular disease. (orig.). With 1 fig., 1 tab.

  11. Preliminary research on abnormal brain detection by wavelet-energy and quantum- behaved PSO.

    Science.gov (United States)

    Zhang, Yudong; Ji, Genlin; Yang, Jiquan; Wang, Shuihua; Dong, Zhengchao; Phillips, Preetha; Sun, Ping

    2016-04-29

    It is important to detect abnormal brains accurately and early. The wavelet-energy (WE) was a successful feature descriptor that achieved excellent performance in various applications; hence, we proposed a WE based new approach for automated abnormal detection, and reported its preliminary results in this study. The kernel support vector machine (KSVM) was used as the classifier, and quantum-behaved particle swarm optimization (QPSO) was introduced to optimize the weights of the SVM. The results based on a 5 × 5-fold cross validation showed the performance of the proposed WE + QPSO-KSVM was superior to ``DWT + PCA + BP-NN'', ``DWT + PCA + RBF-NN'', ``DWT + PCA + PSO-KSVM'', ``WE + BPNN'', ``WE +$ KSVM'', and ``DWT $+$ PCA $+$ GA-KSVM'' w.r.t. sensitivity, specificity, and accuracy. The work provides a novel means to detect abnormal brains with excellent performance.

  12. Congenital brain abnormalities: an update on malformations of cortical development and infratentorial malformations.

    Science.gov (United States)

    Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2014-07-01

    In the past two decades, significant progress in neuroimaging and genetic techniques has allowed for advances in the correct definition/classification of congenital brain abnormalities, which have resulted in a better understanding of their pathogenesis. In addition, new groups of diseases, such as axonal guidance disorders or tubulinopathies, are increasingly reported. Well-defined neuroimaging diagnostic criteria have been suggested for the majority of congenital brain abnormalities. Accurate diagnoses of these complex abnormalities, including distinction between malformations and disruptions, are of paramount significance for management, prognosis, and family counseling. In the next decade, these advances will hopefully be translated into deeper understanding of these disorders and more specific treatments. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Fine print in isotope effects: the glucose anomeric equilibrium and binding of glucose to human brain hexokinase

    International Nuclear Information System (INIS)

    Lewis, B.E; Schramm, V.L.

    2002-01-01

    Binding isotope effects are a sensitive measure of changes in molecular vibrational character that occur during ligand-receptor binding. In this study, we have measured isotope effects on the binding of glucose to human brain hexokinase using the ultrafiltration method, with the following results: 0.991±0.001, 0.908±0.003, 1.010±0.001, 0.974±0.002, 1.022±0.002 for [ 14 C]-glucose mixed with [1- 3 H]-, [2- 3 H]-, [3- 3 H]-, [5- 3 H]-, [6,6- 3 H]-glucose, respectively. Comparing the observed data with isotope effects on the anomeric equilibrium in glucose reported previously proves the existence of binding isotope effects in this system. Preliminary computational results are presented to explain the observed binding isotope effects in terms of hydrogen bond patterns and molecular crowding found in the binary complex of sugar and enzyme. (author)

  14. Generalized decrease in brain glucose metabolism during fasting in humans studied by PET

    International Nuclear Information System (INIS)

    Redies, C.; Hoffer, L.J.; Beil, C.

    1989-01-01

    In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged

  15. Structural brain abnormalities in 12 persons with aniridia [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Madison K. Grant

    2017-09-01

    Full Text Available Background: Aniridia is a disorder predominately caused by heterozygous loss-of-function mutations of the PAX6 gene, which is a transcriptional regulator necessary for normal eye and brain development.  The ocular abnormalities of aniridia have been well characterized, but mounting evidence has implicated brain-related phenotypes as a prominent feature of this disorder as well.  Investigations using neuroimaging in aniridia patients have shown reductions in discrete brain structures and changes in global grey and white matter.  However, limited sample sizes and substantive heterogeneity of structural phenotypes in the brain remain a challenge.  Methods: Here, we examined brain structure in a new population sample in an effort to add to the collective understanding of anatomical abnormalities in aniridia.  The current study used 3T magnetic resonance imaging to acquire high-resolution structural data in 12 persons with aniridia and 12 healthy demographically matched comparison subjects.  Results: We examined five major structures: the anterior commissure, the posterior commissure, the pineal gland, the corpus callosum, and the optic chiasm.  The most consistent reductions were found in the anterior commissure and the pineal gland; however, abnormalities in all of the other structures examined were present in at least one individual.  Conclusions: Our results indicate that the anatomical abnormalities in aniridia are variable and largely individual-specific.  These findings suggest that future studies investigate this heterogeneity further, and that normal population variation should be considered when evaluating structural abnormalities.

  16. Abnormal brain magnetic resonance imaging in two patients with Smith-Magenis syndrome.

    Science.gov (United States)

    Maya, Idit; Vinkler, Chana; Konen, Osnat; Kornreich, Liora; Steinberg, Tamar; Yeshaya, Josepha; Latarowski, Victoria; Shohat, Mordechai; Lev, Dorit; Baris, Hagit N

    2014-08-01

    Smith-Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion in chromosome 17p11.2. Seventy percent of SMS patients have a common deletion interval spanning 3.5 megabases (Mb). Clinical features of SMS include characteristic mild dysmorphic features, ocular anomalies, short stature, brachydactyly, and hypotonia. SMS patients have a unique neurobehavioral phenotype that includes intellectual disability, self-injurious behavior and severe sleep disturbance. Little has been reported in the medical literature about anatomical brain anomalies in patients with SMS. Here we describe two patients with SMS caused by the common deletion in 17p11.2 diagnosed using chromosomal microarray (CMA). Both patients had a typical clinical presentation and abnormal brain magnetic resonance imaging (MRI) findings. One patient had subependymal periventricular gray matter heterotopia, and the second had a thin corpus callosum, a thin brain stem and hypoplasia of the cerebellar vermis. This report discusses the possible abnormal MRI images in SMS and reviews the literature on brain malformations in SMS. Finally, although structural brain malformations in SMS patients are not a common feature, we suggest baseline routine brain imaging in patients with SMS in particular, and in patients with chromosomal microdeletion/microduplication syndromes in general. Structural brain malformations in these patients may affect the decision-making process regarding their management. © 2014 Wiley Periodicals, Inc.

  17. Diffusion tensor MR imaging in neurofibromatosis type 1: expanding the knowledge of microstructural brain abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Ferraz-Filho, Jose R.L.; Muniz, Marcos P.; Souza, Antonio S. [Medical School in Sao Jose do Rio Preto (FAMERP), Radiology Department, Sao Paulo (Brazil); Rocha, Antonio J. da [School Medical Sciences of the Santa Casa de Sao Paulo, Radiology Department, Sao Paulo (Brazil); Goloni-Bertollo, Eny M.; Pavarino-Bertelli, Erika C. [Center of Research and attendace in Neurofibromatosis (CEPAN) of Medical School in Sao Jose do Rio Preto (FAMERP), Sao Paulo (Brazil)

    2012-04-15

    Neurofibromatosis type 1 (NF1) is a hereditary disease with a dominant autosomal pattern. In children and adolescents, it is frequently associated with the appearance of T2-weighted hyperintensities in the brain's white matter. MRI with diffusion tensor imaging (DTI) is used to detect white matter abnormalities by measuring fractional anisotropy (FA). This study employed DTI to evaluate the relationship between FA patterns and the findings of T2 sequences, with the aim of improving our understanding of anatomical changes and microstructural brain abnormalities in individuals with NF1. Forty-four individuals with NF1 and 20 control subjects were evaluated. The comparative analysis of FA between NF1 and control groups was based on four predetermined anatomical regions of the brain hemispheres (basal ganglia, cerebellum, pons, thalamus) and related the presence or absence of T2-weighted hyperintensities in the brain, which are called unidentified bright objects (UBOs). The FA values between the groups demonstrated statistically significant differences (P {<=} 0.05) for the cerebellum and thalamus in patients with NF1, independent of the occurrence of UBOs. Diffusion tensor MR imaging confirms the influence of UBOs in the decrease of FA values in this series of patients with NF1. Additionally, this technique allows the characterization of microstructural abnormalities even in some brain regions that appear normal in conventional MR sequences. (orig.)

  18. Diffusion tensor MR imaging in neurofibromatosis type 1: expanding the knowledge of microstructural brain abnormalities

    International Nuclear Information System (INIS)

    Ferraz-Filho, Jose R.L.; Muniz, Marcos P.; Souza, Antonio S.; Rocha, Antonio J. da; Goloni-Bertollo, Eny M.; Pavarino-Bertelli, Erika C.

    2012-01-01

    Neurofibromatosis type 1 (NF1) is a hereditary disease with a dominant autosomal pattern. In children and adolescents, it is frequently associated with the appearance of T2-weighted hyperintensities in the brain's white matter. MRI with diffusion tensor imaging (DTI) is used to detect white matter abnormalities by measuring fractional anisotropy (FA). This study employed DTI to evaluate the relationship between FA patterns and the findings of T2 sequences, with the aim of improving our understanding of anatomical changes and microstructural brain abnormalities in individuals with NF1. Forty-four individuals with NF1 and 20 control subjects were evaluated. The comparative analysis of FA between NF1 and control groups was based on four predetermined anatomical regions of the brain hemispheres (basal ganglia, cerebellum, pons, thalamus) and related the presence or absence of T2-weighted hyperintensities in the brain, which are called unidentified bright objects (UBOs). The FA values between the groups demonstrated statistically significant differences (P ≤ 0.05) for the cerebellum and thalamus in patients with NF1, independent of the occurrence of UBOs. Diffusion tensor MR imaging confirms the influence of UBOs in the decrease of FA values in this series of patients with NF1. Additionally, this technique allows the characterization of microstructural abnormalities even in some brain regions that appear normal in conventional MR sequences. (orig.)

  19. GLP-1 analog raises glucose transport capacity of blood-brain barrier in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, M.; Brock, B.; Egefjord, L.

    2017-01-01

    Objectives: Glucose enters the brain tissue from plasma by facilitated diffusion across the two membranes of the endothelium of the blood-brain barrier (BBB), mediated by the glucose transporter 1 (GLUT1). There is evidence in Alzheimer's disease (AD) of reduction of glucose transport across...... the blood-brain barrier, due to diminished GLUT1 translocation and expression at the BBB. Reduced BBB GLUT1 expression is known to aggravate AD pathology and further impair cognitive function, implying that GLUT1 may be a potential target of therapy directed towards AD neurovascular dysfunction...... and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here...

  20. Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs

    OpenAIRE

    Ramnanan, Christopher J.; Saraswathi, Viswanathan; Smith, Marta S.; Donahue, E. Patrick; Farmer, Ben; Farmer, Tiffany D.; Neal, Doss; Williams, Philip E.; Lautz, Margaret; Mari, Andrea; Cherrington, Alan D.; Edgerton, Dale S.

    2011-01-01

    In rodents, acute brain insulin action reduces blood glucose levels by suppressing the expression of enzymes in the hepatic gluconeogenic pathway, thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether a similar mechanism is functional in large animals, including humans, is unknown. Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought about by infusion of insulin into the head arteries (during a pancreatic clamp to maintain basal hepatic...

  1. Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation

    DEFF Research Database (Denmark)

    Madsen, P L; Hasselbalch, S G; Hagemann, L P

    1995-01-01

    fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic...

  2. Single abnormal value on 3-hour oral glucose tolerance test during pregnancy is associated with adverse maternal and neonatal outcomes: a systematic review and metaanalysis.

    Science.gov (United States)

    Roeckner, Jared T; Sanchez-Ramos, Luis; Jijon-Knupp, Rubymel; Kaunitz, Andrew M

    2016-09-01

    The purpose of this study was to determine whether women with 1 abnormal value on 3-hour 100-g oral glucose tolerance test are at an increased risk for adverse pregnancy outcomes. Gestational diabetes mellitus is diagnosed by a 2-step method, with a 3-hour, 100-g oral glucose tolerance test that is reserved for women with an abnormal 1-hour, 50-g glucose challenge test. Although the increased maternal-fetal morbidity with gestational diabetes mellitus is well established, controversy remains about the risk that is associated with an isolated abnormal value during a 3-hour, 100-g oral glucose tolerance test. Prospective and retrospective studies that evaluated the maternal and perinatal impact of 1 abnormal glucose value during a 3-hour, 100-g oral glucose tolerance test were identified with the use of computerized databases. Data were extracted and quantitative analyses were performed. Twenty-five studies (7 prospective and 18 retrospective) that met criteria for metaanalysis included 4466 women with 1 abnormal glucose value on oral glucose tolerance test. Patients with 1 abnormal glucose value had significantly worse pregnancy outcomes compared with women with zero abnormal values with the following pooled odds ratios: macrosomia, 1.59 (95% confidence interval, 1.16-2.19); large for gestational age, 1.38 (95% confidence interval, 1.09-1.76); increased mean birthweight, 44.5 g (95% confidence interval, 8.10-80.80 g); neonatal hypoglycemia, 1.88 (95% confidence interval, 1.05-3.38); total cesarean delivery, 1.69 (95% confidence interval, 1.40-2.05); pregnancy-induced hypertension, 1.55 (95% confidence interval, 1.31-1.83), and Apgar score of test (normal glucose screen). With the exception of birthweight, outcomes of patients with 1 abnormal glucose value were similar to outcomes of patients with gestational diabetes mellitus. Women with 1 abnormal value on 3-hour, 100-g oral glucose tolerance test have a significantly increased risk for poor outcomes comparable

  3. Neonatal Brain Abnormalities and Memory and Learning Outcomes at 7 Years in Children Born Very Preterm

    Science.gov (United States)

    Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

    2014-01-01

    Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term born controls. Neonatal brain abnormalities, and in particular deep grey matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children, especially global, white-matter, grey-matter and cerebellar abnormalities. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function. PMID:23805915

  4. Abnormal brain MRI in a case of acute ataxia as the only sign of abdominal neuroblastoma

    International Nuclear Information System (INIS)

    Molla Mohammadi, M.; Karimzadeh, P.; Khatami, A.; Jadali, F.

    2010-01-01

    Ataxia is a movement disorder that may manifest an acute, intermittent, non progressive or chronic progressive course. Ataxia alone is rare as a para neoplastic sign, especially if it is due to neuroblastoma (abdominal or chest). We report an abdominal neuroblastoma in a two-year-old girl presenting with only acute ataxia and abnormal neuroimaging. Brain MRI showed abnormal signal finding in the medulla, pons, cortico spinal tract and the periventricular space. In the abdominal CT, a mass was detected in the right adrenal gland with calcification and the histopathologic examination re-vealed neuroblastoma. We suggest in children with acute ataxia, with or without opalescence-myoclonus, neuroblastoma should be considered.

  5. Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery.

    Science.gov (United States)

    Duarte, João M N; Morgenthaler, Florence D; Gruetter, Rolf

    2017-06-01

    Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.

  6. Quantitative assessment of brain glucose metabolic rates using in vivo deuterium magnetic resonance spectroscopy.

    Science.gov (United States)

    Lu, Ming; Zhu, Xiao-Hong; Zhang, Yi; Mateescu, Gheorghe; Chen, Wei

    2017-11-01

    Quantitative assessment of cerebral glucose consumption rate (CMR glc ) and tricarboxylic acid cycle flux (V TCA ) is crucial for understanding neuroenergetics under physiopathological conditions. In this study, we report a novel in vivo Deuterium ( 2 H) MRS (DMRS) approach for simultaneously measuring and quantifying CMR glc and V TCA in rat brains at 16.4 Tesla. Following a brief infusion of deuterated glucose, dynamic changes of isotope-labeled glucose, glutamate/glutamine (Glx) and water contents in the brain can be robustly monitored from their well-resolved 2 H resonances. Dynamic DMRS glucose and Glx data were employed to determine CMR glc and V TCA concurrently. To test the sensitivity of this method in response to altered glucose metabolism, two brain conditions with different anesthetics were investigated. Increased CMR glc (0.46 vs. 0.28 µmol/g/min) and V TCA (0.96 vs. 0.6 µmol/g/min) were found in rats under morphine as compared to deeper anesthesia using 2% isoflurane. This study demonstrates the feasibility and new utility of the in vivo DMRS approach to assess cerebral glucose metabolic rates at high/ultrahigh field. It provides an alternative MRS tool for in vivo study of metabolic coupling relationship between aerobic and anaerobic glucose metabolisms in brain under physiopathological states.

  7. Specificity of abnormal brain volume in major depressive disorder: a comparison with borderline personality disorder.

    Science.gov (United States)

    Depping, Malte S; Wolf, Nadine D; Vasic, Nenad; Sambataro, Fabio; Thomann, Philipp A; Christian Wolf, R

    2015-03-15

    Abnormal brain volume has been frequently demonstrated in major depressive disorder (MDD). It is unclear if these findings are specific for MDD since aberrant brain structure is also present in disorders with depressive comorbidity and affective dysregulation, such as borderline personality disorder (BPD). In this transdiagnostic study, we aimed to investigate if regional brain volume loss differentiates between MDD and BPD. Further, we tested for associations between brain volume and clinical variables within and between diagnostic groups. 22 Females with a DSM-IV diagnosis of MDD, 17 females with a DSM-IV diagnosis of BPD and without comorbid posttraumatic stress disorder, and 22 age-matched female healthy controls (HC) were investigated using magnetic resonance imaging. High-resolution structural data were analyzed using voxel-based morphometry. A significant (pdisorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. N-terminal pro-brain natriuretic peptide and abnormal brain aging: The AGES-Reykjavik Study.

    Science.gov (United States)

    Sabayan, Behnam; van Buchem, Mark A; de Craen, Anton J M; Sigurdsson, Sigurdur; Zhang, Qian; Harris, Tamara B; Gudnason, Vilmundur; Arai, Andrew E; Launer, Lenore J

    2015-09-01

    To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals. In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI. In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output. Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated. © 2015 American Academy of Neurology.

  9. Paediatrics brain imaging in epilepsy: common presenting symptoms and spectrum of abnormalities detected on MRI

    International Nuclear Information System (INIS)

    Ali, A.; Akram, F.; Khan, G.; Hussain, S.

    2017-01-01

    Epilepsy, a common neurological disorder can present at any age and has a number of aetiologies with underlying brain disease being the most common aetiology. Brain imaging becomes important and mandatory in the work up for epilepsy in localization and lateralization of the seizure focus. Methods: This cross-sectional study was conducted in the department of Radiology Ayub Medical Teaching Institution Abbottabad from 1st March 2015 to 31st March 2016. A total of 209 children aged 28 days to 14 years were included in the study who presented with seizures to clinicians. Information obtained from history, clinical examination and investigations especially MRI brains were recorded in a prescribed pro forma. The data was analysed in SPSS 20. Results: MRI examination was unremarkable in 44.01% (n=92) and mild generalized brain atrophy was noted in 12.91% (n=27). Arachnoid cysts, mild unilateral brain atrophy and hydrocephalous due to aqueduct stenosis were recorded in 3.82% (n=8) of each group. Neoplastic lesions were the second most common abnormal MRI finding and constituted 5.74% (n=12). Leukodystrophy was diagnosed in 4.78% (n=10). MRI examination showed ring enhancing lesions (tuberculomas) and AVM in 1.43% (n=3) of each group. Perinatal ischemia and intracranial infection, (focal or generalized) were recorded in 2.87% (n=6) of each group. A 0.95 % (n=2) of children in each group had agenesis of corpus callosum and cavernoma. The radiological MRI diagnosis of Raussmussen encephalitis was made in 3.34% (n=7). Single case, each of mesial temporal sclerosis, subdural haemorrhage, infarct and craniopharyngioma was recorded making 0.47 % of the total patients in each case. Conclusion: MRI examination was abnormal in significant number of patients (55.86%), so therefore if properly utilized, in a good clinical context, this can identify most of the structural brain abnormalities in paediatric patients presenting with seizures. (author)

  10. Effects of lindane on the glucose metabolism in rat brain cortex cells

    International Nuclear Information System (INIS)

    Pulido, J.A.; del Hoyo, N.; Perez-Albarsanz, M.A.

    1990-01-01

    The influence of 0.5 mM γ-hexachlorocyclohexane (γ-HCH, lindane) on glucose transport has been investigated using the analog 3-O-methyl-D(U- 14 C) glucose. The glucose uptake was lineal for at least 10 sec. Preincubation of dissociated brain cortex cells with lindane decreased the transport of glucose with respect to the controls. The treatment of brain cortex cells with other organochlorine compounds indicated that the α-, δ-HCH isomers and dieldrin reproduced the same inhibitory pattern, while β-HCH and endrin were inactive. The total radioactivity incorporated into CO 2 from (U- 14 C) glucose in the cerebral cortex is also inhibited by lindane in a time dependent manner

  11. Regional brain glucose metabolism and blood flow in streptozocin-induced diabetic rats

    International Nuclear Information System (INIS)

    Jakobsen, J.; Nedergaard, M.; Aarslew-Jensen, M.; Diemer, N.H.

    1990-01-01

    Brain regional glucose metabolism and regional blood flow were measured from autoradiographs by the uptake of [ 3 H]-2-deoxy-D-glucose and [ 14 C]iodoantipyrine in streptozocin-induced diabetic (STZ-D) rats. After 2 days of diabetes, glucose metabolism in the neocortex, basal ganglia, and white matter increased by 34, 37, and 8%, respectively, whereas blood flow was unchanged. After 4 mo, glucose metabolism in the same three regions was decreased by 32, 43, and 60%. This reduction was paralleled by a statistically nonsignificant reduction in blood flow in neocortex and basal ganglia. It is suggested that the decrease of brain glucose metabolism in STZ-D reflects increased ketone body oxidation and reduction of electrochemical work

  12. Serum Lipids and Glucose Abnormalities in HIV/AIDS Patients on ...

    African Journals Online (AJOL)

    METHODS: PLWHA who were regular on ART for at least three months and had pre-treatment CD4+ count, fasting lipid and glucose profiles were grouped into two treatment regimens: protease inhibitor, (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI). Pre and post-exposure metabolic and nonmetabolic ...

  13. Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain.

    Science.gov (United States)

    Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L; Kanekiyo, Takahisa; Bu, Guojun

    2015-04-08

    Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of Aβ in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor β in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. Copyright © 2015 the authors 0270-6474/15/355851-09$15.00/0.

  14. Comparison of brain volume abnormalities between ADHD and conduct disorder in adolescence

    Science.gov (United States)

    Stevens, Michael C.; Haney-Caron, Emily

    2012-01-01

    Background Previous studies of brain structure abnormalities in conduct disorder and attention-deficit/hyperactivity disorder (ADHD) samples have been limited owing to cross-comorbidity, preventing clear understanding of which structural brain abnormalities might be specific to or shared by each disorder. To our knowledge, this study was the first direct comparison of grey and white matter volumes in diagnostically “pure” (i.e., no comorbidities) conduct disorder and ADHD samples. Methods Groups of adolescents with noncormobid conduct disorder and with noncomorbid, combined-subtype ADHD were compared with age- and sex-matched controls using DARTEL voxel-based analysis of T1-weighted brain structure images. Analysis of variance with post hoc analyses compared whole brain grey and white matter volumes among the groups. Results We included 24 adolescents in each study group. There was an overall 13% reduction in grey matter volume in adolescents with conduct disorder, reflecting numerous frontal, temporal, parietal and subcortical deficits. The same grey matter regions typically were not abnormal in those with ADHD. Deficits in frontal lobe regions previously identified in studies of patients with ADHD either were not detected, or group differences from controls were not as strong as those between the conduct disorder and control groups. White matter volume measurements did not differentiate conduct disorder and ADHD. Limitations Our modest sample sizes prevented meaningful examination of individual features of ADHD or conduct disorder, such as aggression, callousness, or hyperactive versus inattentive symptom subtypes. Conclusion The evidence supports theories of frontotemporal abnormalities in adolescents with conduct disorder, but raises questions about the prominence of frontal lobe and striatal structural abnormalities in those with noncomorbid, combined-subtype ADHD. The latter point is clinically important, given the widely held belief that ADHD is

  15. Simultaneous, quantitative measurement of local blood flow and glucose utilization in tissue samples in normal and injured feline brain.

    Science.gov (United States)

    DeWitt, D S; Yuan, X Q; Becker, D P; Hayes, R L

    1988-01-01

    Cerebral blood flow (CBF) and local cerebral glucose utilization (LCGU) were measured using radioactive microspheres and [14C]2-deoxyglucose, respectively, in 26 brain regions in control animals (n = 8) and in animals (n = 4) sustaining low-level experimental brain injury. Examination of the initial (resting) CBF measurement in the uninjured cats revealed two subgroups with significantly (p less than 0.01) different CBF levels. In uninjured cats with normal CBF levels (33.4 +/- 1.8 ml/100 g/min) there was a close linear relationship between CBF and LCGU (n = 0.71, p less than 0.01). In contrast, the remainder of the uninjured cats exhibited abnormally high levels of CBF (72.6 +/- 9.9 ml/100 g/min) and the absence of a close relationship between CBF and LCGU (r = 0.27). One hour following low-level (2.0 atm) fluid percussion brain injury, CBF was increased and LCGU was decreased, though not significantly. The relationship between CBF and LCGU remained intact (r = 0.66, p less than 0.01) in most brain regions. However, the relationship between CBF and LCGU in the hippocampus differed significantly from the relationship between the two parameters in the rest of the brain. Thus, the use of the radioactive microsphere method for CBF measurements allows multiple measurements of CBF and permits the assessment of the status of the cerebral vasculature prior to experimental manipulations such as traumatic brain injury. In view of our current findings of an abnormal relationship between CBF and LCGU in cats with high resting CBF levels, this is an important advantage. In addition, the combination of the microsphere and 2-DG techniques within the same tissue samples allows for the investigation of the effects of traumatic injury on the important relationship between CBF and LCGU.

  16. Effects of Bisphenol A on glucose homeostasis and brain insulin signaling pathways in male mice.

    Science.gov (United States)

    Fang, Fangfang; Chen, Donglong; Yu, Pan; Qian, Wenyi; Zhou, Jing; Liu, Jingli; Gao, Rong; Wang, Jun; Xiao, Hang

    2015-02-01

    The potential effects of Bisphenol A (BPA) on peripheral insulin resistance have recently gained more attention, however, its functions on brain insulin resistance are still unknown. The aim of the present study was to investigate the effects of BPA on insulin signaling and glucose transport in mouse brain. The male mice were administrated of 100 μg/kg/day BPA or vehicle for 15 days then challenged with glucose and insulin tolerance tests. The insulin levels were detected with radioimmunoassay (RIA), and the insulin signaling pathways were investigated by Western blot. Our results revealed that BPA significantly increased peripheral plasma insulin levels, and decreased the insulin signals including phosphorylated insulin receptor (p-IR), phosphorylated insulin receptor substrate 1 (p-IRS1), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular regulated protein kinases (p-ERK1/2) in the brain, though insulin expression in both hippocampus and profrontal cortex was increased. In parallel, BPA exposure might contribute to glucose transport disturbance in the brain since the expression of glucose transporters were markedly decreased. In conclusion, BPA exposure perturbs the insulin signaling and glucose transport in the brain, therefore, it might be a risk factor for brain insulin resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Topography of brain glucose hypometabolism and epileptic network in glucose transporter 1 deficiency.

    Science.gov (United States)

    Akman, Cigdem Inan; Provenzano, Frank; Wang, Dong; Engelstad, Kristin; Hinton, Veronica; Yu, Julia; Tikofsky, Ronald; Ichese, Masonari; De Vivo, Darryl C

    2015-02-01

    (18)F fluorodeoxyglucose positron emission tomography ((18)F FDG-PET) facilitates examination of glucose metabolism. Previously, we described regional cerebral glucose hypometabolism using (18)F FDG-PET in patients with Glucose transporter 1 Deficiency Syndrome (Glut1 DS). We now expand this observation in Glut1 DS using quantitative image analysis to identify the epileptic network based on the regional distribution of glucose hypometabolism. (18)F FDG-PET scans of 16 Glut1 DS patients and 7 healthy participants were examined using Statistical parametric Mapping (SPM). Summed images were preprocessed for statistical analysis using MATLAB 7.1 and SPM 2 software. Region of interest (ROI) analysis was performed to validate SPM results. Visual analysis of the (18)F FDG-PET images demonstrated prominent regional glucose hypometabolism in the thalamus, neocortical regions and cerebellum bilaterally. Group comparison using SPM analysis confirmed that the regional distribution of glucose hypo-metabolism was present in thalamus, cerebellum, temporal cortex and central lobule. Two mildly affected patients without epilepsy had hypometabolism in cerebellum, inferior frontal cortex, and temporal lobe, but not thalamus. Glucose hypometabolism did not correlate with age at the time of PET imaging, head circumference, CSF glucose concentration at the time of diagnosis, RBC glucose uptake, or CNS score. Quantitative analysis of (18)F FDG-PET imaging in Glut1 DS patients confirmed that hypometabolism was present symmetrically in thalamus, cerebellum, frontal and temporal cortex. The hypometabolism in thalamus correlated with the clinical history of epilepsy. Copyright © 2014. Published by Elsevier B.V.

  18. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    International Nuclear Information System (INIS)

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-01-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions

  19. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-05-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.

  20. GLUT-1 GLUCOSE TRANSPORTERS IN THE BLOOD-BRAIN BARRIER: DIFFERENTIAL PHOSPHORYLATION

    Science.gov (United States)

    Devraj, Kavi; Klinger, Marianne E.; Myers, Roland L.; Mokashi, Ashwini; Hawkins, Richard A.; Simpson, Ian A.

    2013-01-01

    Glucose is the primary metabolic fuel for the mammalian brain and a continuous supply is required to maintain normal CNS function. The transport of glucose across the blood-brain barrier (BBB) into the brain is mediated by the facilitative glucose transporter GLUT-1. Prior studies (Simpson et al. 2001) had revealed that the conformations of the GLUT-1 transporter were different in luminal (blood facing) and abluminal (brain facing) membranes of bovine cerebral endothelial cells, based on differential antibody recognition. In this study we have extended these observations and using a combination of 2D-PAGE/Western blotting and immunogold electron microscopy we determined that these different conformations are exhibited in vivo and arise from differential phosphorylation of GLUT-1 and not from alternative splicing or altered O- or N-linked glycosylation. PMID:21910135

  1. Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

    Science.gov (United States)

    Xu, Long-Chun; Zhang, Gang; Zou, Yue; Zhang, Min-Feng; Zhang, Dong-Sheng; Ma, Hua; Zhao, Wen-Bo; Zhang, Guang-Yu

    2017-10-13

    The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

  2. Association of leukocyte count and hsCRP with metabolic abnormalities in subjects with normal glucose tolerance (CURES - 64).

    Science.gov (United States)

    Gokulakrishnan, K; Deepa, R; Sampathkumar, R; Balasubramanyam, M; Mohan, V

    2009-01-01

    The aim of the present study was to assess the association of leukocyte count and high sensitivity C-Reactive protein (hsCRP) with metabolic abnormalities in subjects with normal glucose tolerance. Subjects with Normal Glucose Tolerance (NGT) (n = 865) were recruited from the Chennai Urban Rural Epidemiology Study [CURES]. Standard methods were used for assessing hsCRP [Nephelometry, in a subset] and leukocytes [Flowcytometry, Sysmex SF-3000]. Insulin resistance was calculated using the Homeostasis Assessment model (HOMA-IR). Body mass index, waist circumference, systolic and diastolic blood pressure, fasting plasma glucose, HbA1c, serum cholesterol, LDL cholesterol, HOMA IR and hsCRP increased significantly with increasing tertiles of leukocyte count [p for trend leukocyte count and hsCRP showed a positive correlation with cardiovascular risk factors. Leukocyte count showed a positive correlation with hsCRP [p = 0.008]. Both mean leukocyte count [p leukocyte count [p leukocyte count and hsCRP] and MS/cardiovascular risk factors in Asian Indians even among non-diabetic subjects.

  3. Regional alterations in glucose consumption and metabolite levels during postischemic recovery in cat brain.

    Science.gov (United States)

    Tanaka, K; Welsh, F A; Greenberg, J H; O'Flynn, R; Harris, V A; Reivich, M

    1985-12-01

    Local CMRgl (LCMRgl) and metabolite levels were measured in the same tissue samples following 4 h of recirculation after 1 h of occlusion of the middle cerebral artery in the cat. The rate of glucose utilization was calculated using direct measurement of tissue deoxyglucose-6-phosphate and using a "lumped" constant corrected in each sample for alterations in tissue glucose. Increased LCMRgl (compared with that in sham-operated animals) occurred in regions with only minor alterations in levels of lactate and phosphocreatine. By contrast, LCMRgl was markedly depressed in regions with major changes in lactate and high-energy phosphates. Interestingly, tissue levels of glucose and unphosphorylated deoxyglucose were abnormally elevated in regions with profound energy failure. These results indicate an inhibition of glucose utilization in regions damaged by ischemia, despite the persistent elevation of tissue lactate. Increased glucose metabolism at 4 h post ischemia was detected only in areas with minor anaerobic alteration of metabolite levels.

  4. No abnormalities of intrinsic brain connectivity in the interictal phase of migraine with aura.

    Science.gov (United States)

    Hougaard, A; Amin, F M; Magon, S; Sprenger, T; Rostrup, E; Ashina, M

    2015-04-01

    Functional neuroimaging studies have shown hyperresponsiveness of cortical areas to visual stimuli in migraine patients with aura outside of attacks. This may be a key feature in the initiation of aura episodes and possibly also migraine headache attacks. It is unknown if cortical dysfunction is present at rest, i.e. in the absence of any external stimuli. Functional magnetic resonance imaging is a powerful technique for evaluating resting state functional connectivity, i.e. coherence of brain activity across cerebral areas. The objective of this study was to investigate resting-state functional brain connectivity in migraineurs with aura outside of attacks using functional magnetic resonance imaging. Forty patients suffering from migraine with visual aura and 40 individually age and gender matched healthy controls with no history or family history of migraine were investigated. Following advanced denoising, the data were analyzed both in a hypothesis-driven fashion, testing for abnormalities involving 27 different brain areas of potential relevance to migraine with aura including the cortical visual areas, the amygdala and peri-aqueductal grey matter, and in a data-driven exploratory fashion (dual regression) in order to reveal any possible between-group differences of resting state networks. Age, gender, attack frequency and disease duration were included as nuisance variables. No differences of functional connectivity were found between patients and controls. The previously reported increased cortical hyperresponsivity in the interictal phase of migraine with aura is unlikely to be caused by abnormalities of intrinsic brain connectivity. The interictal migraine aura brain may be abnormally functioning only during exposure to external stimuli. © 2015 EAN.

  5. Relationship between regional brain glucose metabolism and temperament factor of personality

    International Nuclear Information System (INIS)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun

    2005-01-01

    Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24±4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor

  6. Relationship between regional brain glucose metabolism and temperament factor of personality

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24{+-}4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor.

  7. Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

    International Nuclear Information System (INIS)

    Wong, K.L.; Tyce, G.M.

    1983-01-01

    The metabolism of glucose in brains during sustained hypoglycemia was studied. [U- 14 C]Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. In the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia

  8. Positron emission tomography studies in the normal and abnormal ageing of human brain

    International Nuclear Information System (INIS)

    Comar, D.; Baron, J.C.

    1987-01-01

    Until recently, the investigation of the neurophysiological correlates of normal and abnormal ageing of the human brain was limited by methodological constraints, as the technics available provided only a few parameters (e.g. electroencephalograms, cerebral blood flow) monitored in superficial brain structures in a grossly regional and poorly quantitative way. Lately several non invasive techniques have been developed which allow to investigate in vivo both quantitatively and on local basis a number of previously inaccessible important aspects of brain function. Among these techniques, such as single photon emission tomography imaging of computerized electric events, nuclear magnetic resonance, positron emission tomography stands out as the most powerful and promising method since it allows the in vivo measurement of biochemical and pharmacological parameters

  9. Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated insulin secretion via sympathetic innervation.

    Science.gov (United States)

    Tudurí, Eva; Beiroa, Daniel; Stegbauer, Johannes; Fernø, Johan; López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

    2016-11-01

    Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i.c.v.) injection with specific agonists for the three main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors: activation of KOR and DOR did not alter glucose tolerance, whereas activation of brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin secretion (GSIS), reduced insulin sensitivity, increased the expression of gluconeogenic genes in the liver and, consequently, impaired glucose tolerance. Pharmacological blockade of α2A-adrenergic receptors prevented DAMGO-induced glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit GSIS and to impair glucose tolerance in α2A-adrenoceptor knockout mice, indicating that the effects of central MOR activation on β-cells are mediated via sympathetic innervation. Our results show for the first time a new role of the central opioid system, specifically the MOR, in the regulation of insulin secretion and glucose metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Prognostic implications of fasting plasma glucose in subjects with echocardiographic abnormalities

    DEFF Research Database (Denmark)

    Pareek, Manan; Vaduganathan, Muthiah; Bhatt, Deepak L

    2017-01-01

    AIMS: To examine whether baseline fasting plasma glucose (FPG) modifies the prognostic role of left ventricular (LV) mass, geometric pattern, and diastolic function, for prediction of cardiovascular morbidity and mortality. METHODS: Population-based cohort study comprising of 1047 men and 456 women...... with preserved ejection fraction, included between 2002 and 2006, who underwent echocardiography based on groups defined by FPG, measured prior to echocardiography. The clinical endpoint was the composite of cardiovascular events and all-cause mortality, assessed through national and local registries. Cox...... of 8.3years, 449 composite events occurred. FPG (hazard ratio (HR), 1.09 (95% confidence interval (CI): 1.05-1.13), P

  11. Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

    Science.gov (United States)

    Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

    2017-01-01

    Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Added value of fetal MRI in fetuses with suspected brain abnormalities on neurosonography : a systematic review and meta-analysis

    NARCIS (Netherlands)

    van Doorn, Martine; Oude Rengerink, K|info:eu-repo/dai/nl/375367292; Newsum, Esther A; Reneman, Liesbeth; Majoie, Charles B; Pajkrt, Eva

    PURPOSE: To evaluate the additional diagnostic value of fetal Magnetic Resonance Imaging (MRI) in fetuses with suspected brain abnormalities identified with advanced neurosonography (NS). METHODS: A systematic literature search was performed for studies reporting on a comparison between diagnosis

  13. Assessment of abnormal brain structures and networks in major depressive disorder using morphometric and connectome analyses.

    Science.gov (United States)

    Chen, Vincent Chin-Hung; Shen, Chao-Yu; Liang, Sophie Hsin-Yi; Li, Zhen-Hui; Tyan, Yeu-Sheng; Liao, Yin-To; Huang, Yin-Chen; Lee, Yena; McIntyre, Roger S; Weng, Jun-Cheng

    2016-11-15

    It is hypothesized that the phenomenology of major depressive disorder (MDD) is subserved by disturbances in the structure and function of brain circuits; however, findings of structural abnormalities using MRI have been inconsistent. Generalized q-sampling imaging (GQI) methodology provides an opportunity to assess the functional integrity of white matter tracts in implicated circuits. The study population was comprised of 16 outpatients with MDD (mean age 44.81±2.2 years) and 30 age- and gender-matched healthy controls (mean age 45.03±1.88 years). We excluded participants with any other primary mental disorder, substance use disorder, or any neurological illnesses. We used T1-weighted 3D MRI with voxel-based morphometry (VBM) and vertex-wise shape analysis, and GQI with voxel-based statistical analysis (VBA), graph theoretical analysis (GTA) and network-based statistical (NBS) analysis to evaluate brain structure and connectivity abnormalities in MDD compared to healthy controls correlates with clinical measures of depressive symptom severity, Hamilton Depression Rating Scale 17-item (HAMD) and Hospital Anxiety and Depression Scale (HADS). Using VBM and vertex-wise shape analyses, we found significant volumetric decreases in the hippocampus and amygdala among subjects with MDD (pbrain disorder with abnormal circuit structure and connectivity. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Initial investigation of glucose metabolism in mouse brain using enriched 17 O-glucose and dynamic 17 O-MRS.

    Science.gov (United States)

    Borowiak, Robert; Reichardt, Wilfried; Kurzhunov, Dmitry; Schuch, Christian; Leupold, Jochen; Krafft, Axel Joachim; Reisert, Marco; Lange, Thomas; Fischer, Elmar; Bock, Michael

    2017-08-01

    In this initial work, the in vivo degradation of 17 O-labeled glucose was studied during cellular glycolysis. To monitor cellular glucose metabolism, direct 17 O-magnetic resonance spectroscopy (MRS) was used in the mouse brain at 9.4 T. Non-localized spectra were acquired with a custom-built transmit/receive (Tx/Rx) two-turn surface coil and a free induction decay (FID) sequence with a short TR of 5.4 ms. The dynamics of labeled oxygen in the anomeric 1-OH and 6-CH 2 OH groups was detected using a Hankel-Lanczos singular value decomposition (HLSVD) algorithm for water suppression. Time-resolved 17 O-MRS (temporal resolution, 42/10.5 s) was performed in 10 anesthetized (1.25% isoflurane) mice after injection of a 2.2 M solution containing 2.5 mg/g body weight of differently labeled 17 O-glucose dissolved in 0.9% physiological saline. From a pharmacokinetic model fit of the H 2 17 O concentration-time course, a mean apparent cerebral metabolic rate of 17 O-labeled glucose in mouse brain of CMR Glc  = 0.07 ± 0.02 μmol/g/min was extracted, which is of the same order of magnitude as a literature value of 0.26 ± 0.06 μmol/g/min reported by 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET). In addition, we studied the chemical exchange kinetics of aqueous solutions of 17 O-labeled glucose at the C1 and C6 positions with dynamic 17 O-MRS. In conclusion, the results of the exchange and in vivo experiments demonstrate that the C6- 17 OH label in the 6-CH 2 OH group is transformed only glycolytically by the enzyme enolase into the metabolic end-product H 2 17 O, whereas C1- 17 OH ends up in water via direct hydrolysis as well as glycolysis. Therefore, dynamic 17 O-MRS of highly labeled 17 O-glucose could provide a valuable non-radioactive alternative to FDG PET in order to investigate glucose metabolism. Copyright © 2017 John Wiley & Sons, Ltd.

  15. The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer.

    Science.gov (United States)

    Meidenbauer, Joshua J; Mukherjee, Purna; Seyfried, Thomas N

    2015-01-01

    Metabolic therapy using ketogenic diets (KD) is emerging as an alternative or complementary approach to the current standard of care for brain cancer management. This therapeutic strategy targets the aerobic fermentation of glucose (Warburg effect), which is the common metabolic malady of most cancers including brain tumors. The KD targets tumor energy metabolism by lowering blood glucose and elevating blood ketones (β-hydroxybutyrate). Brain tumor cells, unlike normal brain cells, cannot use ketone bodies effectively for energy when glucose becomes limiting. Although plasma levels of glucose and ketone bodies have been used separately to predict the therapeutic success of metabolic therapy, daily glucose levels can fluctuate widely in brain cancer patients. This can create difficulty in linking changes in blood glucose and ketones to efficacy of metabolic therapy. A program was developed (Glucose Ketone Index Calculator, GKIC) that tracks the ratio of blood glucose to ketones as a single value. We have termed this ratio the Glucose Ketone Index (GKI). The GKIC was used to compute the GKI for data published on blood glucose and ketone levels in humans and mice with brain tumors. The results showed a clear relationship between the GKI and therapeutic efficacy using ketogenic diets and calorie restriction. The GKIC is a simple tool that can help monitor the efficacy of metabolic therapy in preclinical animal models and in clinical trials for malignant brain cancer and possibly other cancers that express aerobic fermentation.

  16. Exercise, Energy Intake, Glucose Homeostasis, and the Brain

    Science.gov (United States)

    van Praag, Henriette; Fleshner, Monika; Schwartz, Michael W.

    2014-01-01

    Here we summarize topics covered in an SFN symposium that considered how and why exercise and energy intake affect neuroplasticity and, conversely, how the brain regulates peripheral energy metabolism. This article is not a comprehensive review of the subject, but rather a view of how the authors' findings fit into a broader context. Emerging findings elucidate cellular and molecular mechanisms by which exercise and energy intake modify the plasticity of neural circuits in ways that affect brain health. By enhancing neurogenesis, synaptic plasticity and neuronal stress robustness, exercise and intermittent energy restriction/fasting may optimize brain function and forestall metabolic and neurodegenerative diseases. Moreover, brain-centered glucoregulatory and immunomodulating systems that mediate peripheral health benefits of intermittent energetic challenges have recently been described. A better understanding of adaptive neural response pathways activated by energetic challenges will enable the development and optimization of interventions to reduce the burden of disease in our communities. PMID:25392482

  17. Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs

    Science.gov (United States)

    Ramnanan, Christopher J.; Saraswathi, Viswanathan; Smith, Marta S.; Donahue, E. Patrick; Farmer, Ben; Farmer, Tiffany D.; Neal, Doss; Williams, Philip E.; Lautz, Margaret; Mari, Andrea; Cherrington, Alan D.; Edgerton, Dale S.

    2011-01-01

    In rodents, acute brain insulin action reduces blood glucose levels by suppressing the expression of enzymes in the hepatic gluconeogenic pathway, thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether a similar mechanism is functional in large animals, including humans, is unknown. Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought about by infusion of insulin into the head arteries (during a pancreatic clamp to maintain basal hepatic insulin and glucagon levels) activated hypothalamic Akt, altered STAT3 signaling in the liver, and suppressed hepatic gluconeogenic gene expression without altering EGP or gluconeogenesis. Rather, brain hyperinsulinemia slowly caused a modest reduction in net hepatic glucose output (NHGO) that was attributable to increased net hepatic glucose uptake and glycogen synthesis. This was associated with decreased levels of glycogen synthase kinase 3β (GSK3β) protein and mRNA and with decreased glycogen synthase phosphorylation, changes that were blocked by hypothalamic PI3K inhibition. Therefore, we conclude that the canine brain senses physiologic elevations in plasma insulin, and that this in turn regulates genetic events in the liver. In the context of basal insulin and glucagon levels at the liver, this input augments hepatic glucose uptake and glycogen synthesis, reducing NHGO without altering EGP. PMID:21865644

  18. Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs.

    Science.gov (United States)

    Ramnanan, Christopher J; Saraswathi, Viswanathan; Smith, Marta S; Donahue, E Patrick; Farmer, Ben; Farmer, Tiffany D; Neal, Doss; Williams, Philip E; Lautz, Margaret; Mari, Andrea; Cherrington, Alan D; Edgerton, Dale S

    2011-09-01

    In rodents, acute brain insulin action reduces blood glucose levels by suppressing the expression of enzymes in the hepatic gluconeogenic pathway, thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether a similar mechanism is functional in large animals, including humans, is unknown. Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought about by infusion of insulin into the head arteries (during a pancreatic clamp to maintain basal hepatic insulin and glucagon levels) activated hypothalamic Akt, altered STAT3 signaling in the liver, and suppressed hepatic gluconeogenic gene expression without altering EGP or gluconeogenesis. Rather, brain hyperinsulinemia slowly caused a modest reduction in net hepatic glucose output (NHGO) that was attributable to increased net hepatic glucose uptake and glycogen synthesis. This was associated with decreased levels of glycogen synthase kinase 3β (GSK3β) protein and mRNA and with decreased glycogen synthase phosphorylation, changes that were blocked by hypothalamic PI3K inhibition. Therefore, we conclude that the canine brain senses physiologic elevations in plasma insulin, and that this in turn regulates genetic events in the liver. In the context of basal insulin and glucagon levels at the liver, this input augments hepatic glucose uptake and glycogen synthesis, reducing NHGO without altering EGP.

  19. Effect of Toxoplasma gondii infection on glucose metabolism in the brain of pregnant rats by [18F]FDG microPET imaging

    International Nuclear Information System (INIS)

    Fei Xu; Xina Meng; Tingshu Xu; Ting Zhang; Mudan Lu; Hongxiang Zhuge

    2014-01-01

    Toxoplasma gondii (T. gondii) is a pathogenic protozoan parasite, infection of which in early pregnancy increases the risk of serious sequelae in fetus. The aim of this study is to investigate the effect of T. gondii infection on glucose metabolism in the brain of pregnant rats by microPET using 18 F-fluorodeoxygulcose ( 18 F-FDG) as the tracer. Thirty female SD rats were divided into the T. gondii infection and control group. After set for pregnancy, the body weight was assessed, T. gondii infection was identified by PCR, ELISA technology and immunohistochemistry, and glucose metabolism in brain of rats was monitored by microPET scan. Our results showed that brain glucose metabolism was significantly increased in T. gondii-infected group comparing to the control, indicating microPET scan is more sensitive to detect the abnormality than traditional measurements. In addition, bio-distribution of 18 F-FDG in T. gondii-infected rats was assessed by using another twenty female SD rats, which has higher uptake of 18 F-FDG at 30 min after injection in whole brain. Furthermore, the expression profile of GLUT1 was also higher in the brain of pregnant rats of the infected group. Therefore, microPET can be effectively applied to in vivo assessment of small animals and contributes to early diagnosis of T. gondii infection, which also assists in understanding birth defects caused by T. gondii infection. (author)

  20. Motor-related brain abnormalities in HIV-infected patients. A multimodal MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yawen; Wang, Xiaoxiao; Miao, Hui; Wei, Yarui; Ali, Rizwan [University of Science and Technology of China, Centers for Biomedical Engineering, Hefei, Anhui (China); Li, Ruili; Li, Hongjun [Capital Medical University, Department of Radiology, Beijing Youan Hospital, Beijing (China); Qiu, Bensheng [University of Science and Technology of China, Centers for Biomedical Engineering, Hefei, Anhui (China); Anhui Computer Application Institute of Traditional Chinese Medicine, Hefei, Anhui (China)

    2017-11-15

    It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND. (orig.)

  1. Brain structure abnormalities in young women who presented conduct disorder in childhood/adolescence.

    Science.gov (United States)

    Budhiraja, Meenal; Savic, Ivanka; Lindner, Philip; Jokinen, Jussi; Tiihonen, Jari; Hodgins, Sheilagh

    2017-08-01

    The phenotype and genotype of antisocial behavior among females are different from those among males. Previous studies have documented structural brain alterations in males with antisocial behavior, yet little is known about the neural correlates of female antisocial behavior. The present study examined young women who had presented conduct disorder (CDW) prior to age 15 to determine whether brain abnormalities are present in adulthood and whether the observed abnormalities are associated with comorbid disorders or maltreatment that typically characterize this population. Using magnetic resonance imaging and voxel-based morphometry, we compared gray matter volumes (GMV) of 31 women who presented CD by midadolescence and 25 healthy women (HW), age, on average, 23 years. Participants completed structured, validated interviews to diagnose mental disorders, and validated questionnaires to document physical and sexual abuse. Relative to HW, CDW presented increased GMV in the left superior temporal gyrus that was associated with past alcohol and drug dependence, current use of alcohol and drugs, and current anxiety and depression symptoms and maltreatment. Additionally, CDW displayed reduced GMV in lingual gyrus, hippocampus, and anterior cingulate cortex that was associated with past comorbid disorders, current alcohol and drugs use, current anxiety and depression symptoms, and maltreatment. The CDW also presented reduced total GMV that was associated with past comorbid disorders and current anxiety/depression symptoms. Alterations of brain structure were observed among young adult females with prior CD, relative to HW, all of which were associated with internalizing and externalizing disorders and maltreatment that typically accompany CD.

  2. Motor-related brain abnormalities in HIV-infected patients. A multimodal MRI study

    International Nuclear Information System (INIS)

    Zhou, Yawen; Wang, Xiaoxiao; Miao, Hui; Wei, Yarui; Ali, Rizwan; Li, Ruili; Li, Hongjun; Qiu, Bensheng

    2017-01-01

    It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND. (orig.)

  3. Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors

    Science.gov (United States)

    Haziza, Simon; Mohan, Nitin; Loe-Mie, Yann; Lepagnol-Bestel, Aude-Marie; Massou, Sophie; Adam, Marie-Pierre; Le, Xuan Loc; Viard, Julia; Plancon, Christine; Daudin, Rachel; Koebel, Pascale; Dorard, Emilie; Rose, Christiane; Hsieh, Feng-Jen; Wu, Chih-Che; Potier, Brigitte; Herault, Yann; Sala, Carlo; Corvin, Aiden; Allinquant, Bernadette; Chang, Huan-Cheng; Treussart, François; Simonneau, Michel

    2017-05-01

    Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities. Here we report a sensitive method to measure the changes in intraneuronal transport induced by brain-disease-related genetic risk factors using fluorescent nanodiamonds (FNDs). We show that the high brightness, photostability and absence of cytotoxicity allow FNDs to be tracked inside the branches of dissociated neurons with a spatial resolution of 12 nm and a temporal resolution of 50 ms. As proof of principle, we applied the FND tracking assay on two transgenic mouse lines that mimic the slight changes in protein concentration (∼30%) found in the brains of patients. In both cases, we show that the FND assay is sufficiently sensitive to detect these changes.

  4. Brain gene expression differences are associated with abnormal tail biting behavior in pigs.

    Science.gov (United States)

    Brunberg, E; Jensen, P; Isaksson, A; Keeling, L J

    2013-03-01

    Knowledge about gene expression in animals involved in abnormal behaviors can contribute to the understanding of underlying biological mechanisms. This study aimed to explore the motivational background to tail biting, an abnormal injurious behavior and severe welfare problem in pig production. Affymetrix microarrays were used to investigate gene expression differences in the hypothalamus and prefrontal cortex of pigs performing tail biting, pigs receiving bites to the tail and neutral pigs who were not involved in the behavior. In the hypothalamus, 32 transcripts were differentially expressed (P biting behavior as performers or receivers. Among these 19 transcripts were genes associated with production traits in pigs (PDK4), sociality in humans and mice (GTF2I) and novelty seeking in humans (EGF). These are in line with hypotheses linking tail biting with reduced back fat thickness and explorative behavior. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  5. Abnormal brain connectivity patterns in adults with ADHD: a coherence study.

    Directory of Open Access Journals (Sweden)

    João Ricardo Sato

    Full Text Available Studies based on functional magnetic resonance imaging (fMRI during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC and regions of the Default Mode Network (DMN in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD relative to subjects with typical development (TD. Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC in three groups (adult patients with ADHD, n=21; TD age-matched subjects, n=21; young TD subjects, n=21 using a more comprehensive analytical approach - unsupervised machine learning using a one-class support vector machine (OC-SVM that quantifies an abnormality index for each individual. The median abnormality index for patients with ADHD was greater than for TD age-matched subjects (p=0.014; the ADHD and young TD indices did not differ significantly (p=0.480; the median abnormality index of young TD was greater than that of TD age-matched subjects (p=0.016. Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. In addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits.

  6. Chemical exchange-sensitive spin-lock MRI of glucose analog 3-O-methyl-d-glucose in normal and ischemic brain.

    Science.gov (United States)

    Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

    2018-05-01

    Glucose transport is important for understanding brain glucose metabolism. We studied glucose transport with a presumably non-toxic and non-metabolizable glucose analog, 3-O-methyl-d-glucose, using a chemical exchange-sensitive spin-lock MRI technique at 9.4 Tesla. 3-O-methyl-d-glucose showed comparable chemical exchange properties with d-glucose and 2-deoxy-d-glucose in phantoms, and higher and lower chemical exchange-sensitive spin-lock sensitivity than Glc and 2-deoxy-d-glucose in in vivo experiments, respectively. The changes of the spin-lattice relaxation rate in the rotating frame (Δ R 1 ρ) in normal rat brain peaked at ∼15 min after the intravenous injection of 1 g/kg 3-O-methyl-d-glucose and almost maintained a plateau for >1 h. Doses up to 4 g/kg 3-O-methyl-d-glucose were linearly correlated with Δ R 1 ρ. In rats with focal ischemic stroke, chemical exchange-sensitive spin-lock with 3-O-methyl-d-glucose injection at 1 h after stroke onset showed reduced Δ R 1 ρ in the ischemic core but higher Δ R 1 ρ in the peri-core region compared to normal tissue, which progressed into the ischemic core at 3 h after stroke onset. This suggests that the hyper-chemical exchange-sensitive spin-lock region observed at 1 h is the ischemic penumbra at-risk of infarct. In summary, 3-O-methyl-d-glucose-chemical exchange-sensitive spin-lock can be a sensitive MRI technique to probe the glucose transport in normal and ischemic brains.

  7. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer.

    Science.gov (United States)

    Seyfried, T N; Sanderson, T M; El-Abbadi, M M; McGowan, R; Mukherjee, P

    2003-10-06

    Brain tumours lack metabolic versatility and are dependent largely on glucose for energy. This contrasts with normal brain tissue that can derive energy from both glucose and ketone bodies. We examined for the first time the potential efficacy of dietary therapies that reduce plasma glucose and elevate ketone bodies in the CT-2A syngeneic malignant mouse astrocytoma. C57BL/6J mice were fed either a standard diet unrestricted (SD-UR), a ketogenic diet unrestricted (KD-UR), the SD restricted to 40% (SD-R), or the KD restricted to 40% of the control standard diet (KD-R). Body weights, tumour weights, plasma glucose, beta-hydroxybutyrate (beta-OHB), and insulin-like growth factor 1 (IGF-1) were measured 13 days after tumour implantation. CT-2A growth was rapid in both the SD-UR and KD-UR groups, but was significantly reduced in both the SD-R and KD-R groups by about 80%. The results indicate that plasma glucose predicts CT-2A growth and that growth is dependent more on the amount than on the origin of dietary calories. Also, restriction of either diet significantly reduced the plasma levels of IGF-1, a biomarker for angiogenesis and tumour progression. Owing to a dependence on plasma glucose, IGF-1 was also predictive of CT-2A growth. Ketone bodies are proposed to reduce stromal inflammatory activities, while providing normal brain cells with a nonglycolytic high-energy substrate. Our results in a mouse astrocytoma suggest that malignant brain tumours are potentially manageable with dietary therapies that reduce glucose and elevate ketone bodies.

  8. Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

    Science.gov (United States)

    Glenn, Thomas C; Martin, Neil A; McArthur, David L; Hovda, David A; Vespa, Paul; Johnson, Matthew L; Horning, Michael A; Brooks, George A

    2015-06-01

    We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-(2)H2]glucose, i.e., D2-glucose, and [3-(13)C]lactate) techniques involving central venous tracer infusion along with cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Patients with traumatic brain injury (TBI) who had nonpenetrating head injuries (n=12, all male) were entered into the study after consent of patients' legal representatives. Written and informed consent was obtained from healthy controls (n=6, including one female). As in previous investigations, the cerebral metabolic rate (CMR) for glucose was suppressed after TBI. Near normal arterial glucose and lactate levels in patients studied 5.7±2.2 days (range of days 2-10) post-injury, however, belied a 71% increase in systemic lactate production, compared with control, that was largely cleared by greater (hepatic+renal) glucose production. After TBI, gluconeogenesis from lactate clearance accounted for 67.1% of glucose rate of appearance (Ra), which was compared with 15.2% in healthy controls. We conclude that elevations in blood glucose concentration after TBI result from a massive mobilization of lactate from corporeal glycogen reserves. This previously unrecognized mobilization of lactate subserves hepatic and renal gluconeogenesis. As such, a lactate shuttle mechanism indirectly makes substrate available for the body and its essential organs, including the brain, after trauma. In addition, when elevations in arterial lactate concentration occur after TBI, lactate shuttling may provide substrate directly to vital organs of the body, including the injured brain.

  9. A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats

    Directory of Open Access Journals (Sweden)

    Motoyama Caio SM

    2011-09-01

    Full Text Available Abstract Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H or the alternation of chow (C and an H diet (CH regimen induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.

  10. Cerebral abnormalities in cocaine abusers: Demonstration by SPECT perfusion brain scintigraphy. Work in progress

    International Nuclear Information System (INIS)

    Tumeh, S.S.; Nagel, J.S.; English, R.J.; Moore, M.; Holman, B.L.

    1990-01-01

    Single photon emission computed tomography (SPECT) perfusion brain scans with iodine-123 isopropyl iodoamphetamine (IMP) were obtained in 12 subjects who acknowledged using cocaine on a sporadic to a daily basis. The route of cocaine administration varied from nasal to intravenous. Concurrent abuse of other drugs was also reported. None of the patients were positive for human immunodeficiency virus. Brain scans demonstrated focal defects in 11 subjects, including seven who were asymptomatic, and no abnormality in one. Among the findings were scattered focal cortical deficits, which were seen in several patients and which ranged in severity from small and few to multiple and large, with a special predilection for the frontal and temporal lobes. No perfusion deficits were seen on I-123 SPECT images in five healthy volunteers. Focal alterations in cerebral perfusion are seen commonly in asymptomatic drug users, and these focal deficits are readily depicted by I-123 IMP SPECT

  11. Structural brain abnormalities in the frontostriatal system and cerebellum in pedophilia.

    Science.gov (United States)

    Schiffer, Boris; Peschel, Thomas; Paul, Thomas; Gizewski, Elke; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Krueger, Tillmann H C

    2007-11-01

    Even though previous neuropsychological studies and clinical case reports have suggested an association between pedophilia and frontocortical dysfunction, our knowledge about the neurobiological mechanisms underlying pedophilia is still fragmentary. Specifically, the brain morphology of such disorders has not yet been investigated using MR imaging techniques. Whole brain structural T1-weighted MR images from 18 pedophile patients (9 attracted to males, 9 attracted to females) and 24 healthy age-matched control subjects (12 hetero- and 12 homosexual) from a comparable socioeconomic stratum were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. Compared to the homosexual and heterosexual control subjects, pedophiles showed decreased gray matter volume in the ventral striatum (also extending into the nucl. accumbens), the orbitofrontal cortex and the cerebellum. These observations further indicate an association between frontostriatal morphometric abnormalities and pedophilia. In this respect these findings may support the hypothesis that there is a shared etiopathological mechanism in all obsessive-compulsive spectrum disorders.

  12. Comparing CAT12 and VBM8 for Detecting Brain Morphological Abnormalities in Temporal Lobe Epilepsy

    Directory of Open Access Journals (Sweden)

    Farnaz Farokhian

    2017-08-01

    Full Text Available The identification of the brain morphological alterations that play important roles in neurodegenerative/neurological diseases will contribute to our understanding of the causes of these diseases. Various automated software programs are designed to provide an automatic framework to detect brain morphological changes in structural magnetic resonance imaging (MRI data. A voxel-based morphometry (VBM analysis can also be used for the detection of brain volumetric abnormalities. Here, we compared gray matter (GM and white matter (WM abnormality results obtained by a VBM analysis using the Computational Anatomy Toolbox (CAT12 via the current version of Statistical Parametric Mapping software (SPM12 with the results obtained by a VBM analysis using the VBM8 toolbox implemented in the older software SPM8, in adult temporal lobe epilepsy (TLE patients with (n = 51 and without (n = 57 hippocampus sclerosis (HS, compared to healthy adult controls (n = 28. The VBM analysis using CAT12 showed that compared to the healthy controls, significant GM and WM reductions were located in ipsilateral mesial temporal lobes in the TLE-HS patients, and slight GM amygdala swelling was present in the right TLE-no patients (n = 27. In contrast, the VBM analysis via the VBM8 toolbox showed significant GM and WM reductions only in the left TLE-HS patients (n = 25 compared to the healthy controls. Our findings thus demonstrate that compared to VBM8, a VBM analysis using CAT12 provides a more accurate volumetric analysis of the brain regions in TLE. Our results further indicate that a VBM analysis using CAT12 is more robust and accurate against volumetric alterations than the VBM8 toolbox.

  13. Abnormal structural connectivity in the brain networks of children with hydrocephalus

    Directory of Open Access Journals (Sweden)

    Weihong Yuan

    2015-01-01

    Full Text Available Increased intracranial pressure and ventriculomegaly in children with hydrocephalus are known to have adverse effects on white matter structure. This study seeks to investigate the impact of hydrocephalus on topological features of brain networks in children. The goal was to investigate structural network connectivity, at both global and regional levels, in the brains in children with hydrocephalus using graph theory analysis and diffusion tensor tractography. Three groups of children were included in the study (29 normally developing controls, 9 preoperative hydrocephalus patients, and 17 postoperative hydrocephalus patients. Graph theory analysis was applied to calculate the global network measures including small-worldness, normalized clustering coefficients, normalized characteristic path length, global efficiency, and modularity. Abnormalities in regional network parameters, including nodal degree, local efficiency, clustering coefficient, and betweenness centrality, were also compared between the two patients groups (separately and the controls using two tailed t-test at significance level of p < 0.05 (corrected for multiple comparison. Children with hydrocephalus in both the preoperative and postoperative groups were found to have significantly lower small-worldness and lower normalized clustering coefficient than controls. Children with hydrocephalus in the postoperative group were also found to have significantly lower normalized characteristic path length and lower modularity. At regional level, significant group differences (or differences at trend level in regional network measures were found between hydrocephalus patients and the controls in a series of brain regions including the medial occipital gyrus, medial frontal gyrus, thalamus, cingulate gyrus, lingual gyrus, rectal gyrus, caudate, cuneus, and insular. Our data showed that structural connectivity analysis using graph theory and diffusion tensor tractography is sensitive to

  14. Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucose Metabolism

    Science.gov (United States)

    Volkow, Nora D.; Tomasi, Dardo; Wang, Gene-Jack; Vaska, Paul; Fowler, Joanna S.; Telang, Frank; Alexoff, Dave; Logan, Jean; Wong, Christopher

    2011-01-01

    Context The dramatic increase in use of cellular telephones has generated concern about possible negative effects of radiofrequency signals delivered to the brain. However, whether acute cell phone exposure affects the human brain is unclear. Objective To evaluate if acute cell phone exposure affects brain glucose metabolism, a marker of brain activity. Design, Setting, and Participants Randomized crossover study conducted between January 1 and December 31, 2009, at a single US laboratory among 47 healthy participants recruited from the community. Cell phones were placed on the left and right ears and positron emission tomography with (18F)fluorodeoxyglucose injection was used to measure brain glucose metabolism twice, once with the right cell phone activated (sound muted) for 50 minutes (“on” condition) and once with both cell phones deactivated (“off” condition). Statistical parametric mapping was used to compare metabolism between on and off conditions using paired t tests, and Pearson linear correlations were used to verify the association of metabolism and estimated amplitude of radiofrequency-modulated electromagnetic waves emitted by the cell phone. Clusters with at least 1000 voxels (volume >8 cm3) and P cell phone exposure was associated with increased brain glucose metabolism in the region closest to the antenna. This finding is of unknown clinical significance. PMID:21343580

  15. Glucose Administration Enhances fMRI Brain Activation and Connectivity Related to Episodic Memory Encoding for Neutral and Emotional Stimuli

    Science.gov (United States)

    Parent, Marise B.; Krebs-Kraft, Desiree L.; Ryan, John P.; Wilson, Jennifer S.; Harenski, Carla; Hamann, Stephan

    2011-01-01

    Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with…

  16. Brain Microstructural Abnormalities Are Related to Physiological Alterations in End-Stage Renal Disease.

    Directory of Open Access Journals (Sweden)

    Zhigang Bai

    Full Text Available To study whole-brain microstructural alterations in patients with end-stage renal disease (ESRD and examine the relationship between brain microstructure and physiological indictors in the disease.Diffusion tensor imaging data were collected from 35 patients with ESRD (28 men, 18-61 years and 40 age- and gender-matched healthy controls (HCs, 32 men, 22-58 years. A voxel-wise analysis was then used to identify microstructural alterations over the whole brain in the ESRD patients compared with the HCs. Multiple biochemical measures of renal metabolin, vascular risk factors, general cognitive ability and dialysis duration were correlated with microstructural integrity for the patients.Compared to the HCs, the ESRD patients exhibited disrupted microstructural integrity in not only white matter (WM but also gray matter (GM regions, as characterized by decreased fractional anisotropy (FA and increased mean diffusivity (MD, axial diffusivity (AD and radial diffusivity (RD. Further correlation analyses revealed that the in MD, AD and RD values showed significantly positive correlations with the blood urea nitrogen in the left superior temporal gyrus and significantly negative correlations with the calcium levels in the left superior frontal gyrus (orbital part in the patients.Our findings suggest that ESRD is associated with widespread diffusion abnormalities in both WM and GM regions in the brain, and microstructural integrity of several GM regions are related to biochemical alterations in the disease.

  17. Three-dimensional textural analysis of brain images reveals distributed grey-matter abnormalities in schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Ganeshan, Balaji [University of Sussex, Falmer, Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton (United Kingdom); University of Sussex, Falmer, Department of Engineering and Design, Brighton (United Kingdom); Miles, Kenneth A.; Critchley, Hugo D. [University of Sussex, Falmer, Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton (United Kingdom); Young, Rupert C.D.; Chatwin, Christopher R. [University of Sussex, Falmer, Department of Engineering and Design, Brighton (United Kingdom); Gurling, Hugh M.D. [University College London, Department of Mental Health Sciences, London (United Kingdom)

    2010-04-15

    Three-dimensional (3-D) selective- and relative-scale texture analysis (TA) was applied to structural magnetic resonance (MR) brain images to quantify the presence of grey-matter (GM) and white-matter (WM) textural abnormalities associated with schizophrenia. Brain TA comprised volume filtration using the Laplacian of Gaussian filter to highlight fine, medium and coarse textures within GM and WM, followed by texture quantification. Relative TA (e.g. ratio of fine to medium) was also computed. T1-weighted MR whole-brain images from 32 participants with diagnosis of schizophrenia (n = 10) and healthy controls (n = 22) were examined. Five patients possessed marker alleles (SZ8) associated with schizophrenia on chromosome 8 in the pericentriolar material 1 gene while the remaining five had not inherited any of the alleles (SZ0). Filtered fine GM texture (mean grey-level intensity; MGI) most significantly differentiated schizophrenic patients from controls (P = 0.0058; area under the receiver-operating characteristic curve = 0.809, sensitivity = 90%, specificity = 70%). WM measurements did not distinguish the two groups. Filtered GM and WM textures (MGI) correlated with total GM and WM volume respectively. Medium-to-coarse GM entropy distinguished SZ0 from controls (P = 0.0069) while measures from SZ8 were intermediate between the two. 3-D TA of brain MR enables detection of subtle distributed morphological features associated with schizophrenia, determined partly by susceptibility genes. (orig.)

  18. Three-dimensional textural analysis of brain images reveals distributed grey-matter abnormalities in schizophrenia

    International Nuclear Information System (INIS)

    Ganeshan, Balaji; Miles, Kenneth A.; Critchley, Hugo D.; Young, Rupert C.D.; Chatwin, Christopher R.; Gurling, Hugh M.D.

    2010-01-01

    Three-dimensional (3-D) selective- and relative-scale texture analysis (TA) was applied to structural magnetic resonance (MR) brain images to quantify the presence of grey-matter (GM) and white-matter (WM) textural abnormalities associated with schizophrenia. Brain TA comprised volume filtration using the Laplacian of Gaussian filter to highlight fine, medium and coarse textures within GM and WM, followed by texture quantification. Relative TA (e.g. ratio of fine to medium) was also computed. T1-weighted MR whole-brain images from 32 participants with diagnosis of schizophrenia (n = 10) and healthy controls (n = 22) were examined. Five patients possessed marker alleles (SZ8) associated with schizophrenia on chromosome 8 in the pericentriolar material 1 gene while the remaining five had not inherited any of the alleles (SZ0). Filtered fine GM texture (mean grey-level intensity; MGI) most significantly differentiated schizophrenic patients from controls (P = 0.0058; area under the receiver-operating characteristic curve = 0.809, sensitivity = 90%, specificity = 70%). WM measurements did not distinguish the two groups. Filtered GM and WM textures (MGI) correlated with total GM and WM volume respectively. Medium-to-coarse GM entropy distinguished SZ0 from controls (P = 0.0069) while measures from SZ8 were intermediate between the two. 3-D TA of brain MR enables detection of subtle distributed morphological features associated with schizophrenia, determined partly by susceptibility genes. (orig.)

  19. TUBA1A Mutation Associated With Eye Abnormalities in Addition to Brain Malformation.

    Science.gov (United States)

    Myers, Kenneth A; Bello-Espinosa, Luis E; Kherani, Amin; Wei, Xing-Chang; Innes, Allan Micheil

    2015-11-01

    We describe the case of a boy with a TUBA1A mutation presenting with microphthalmia and congenital cataracts in addition to microcephaly and severe brain malformation. A boy presented in early infancy with microphthalmia, congenital cataracts, and microcephaly. His neurological course included severe hypotonia and drug-resistant epilepsy. Magnetic resonance imaging of the brain revealed a complex malformation that included agenesis of the corpus callosum, severely hypoplastic cerebellar vermis, mildly hypoplastic and dysplastic cerebellar hemispheres, mildly hypoplastic brainstem, mild posterior simplified cerebral gyral pattern, dysplastic basal ganglia and thalami, hypoplastic optic nerves, and absent olfactory bulbs. TUBA1A genetic testing was conducted and revealed a previously unreported heterozygous 808G>T missense mutation. Parental genetic testing was negative, indicating that the child's mutation was de novo. The TUBA1A gene encodes tubulin alpha-1A, a protein with an important role in microtubule function and stability. Human mutations can result in a wide spectrum of brain malformations including lissencephaly, microlissencephaly, cerebellar hypoplasia, agenesis of the corpus callosum, pachygyria and polymicrogyria. Although TUBA1A is expressed in both developing brain and retinal tissue, there are no reported cases of TUBA1A mutations in association with major developmental ophthalmologic abnormalities. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. A simple method for measuring glucose utilization of insulin-sensitive tissues by using the brain as a reference

    International Nuclear Information System (INIS)

    Namba, Hiroki; Nakagawa, Keiichi; Iyo, Masaomi; Fukushi, Kiyoshi; Irie, Toshiaki

    1994-01-01

    A simple method, without measurement of the plasma input function, to obtain semiquantitative values of glucose utilization in tissues other than the brain with radioactive deoxyglucose is reported. The brain, in which glucose utilization is essentially insensitive to plasma glucose and insulin concentrations, was used as an internal reference. The effects of graded doses of oral glucose loading (0.5, 1 and 2 mg/g body weight) on insulin-sensitive tissues (heart, muscle and fat tissue) were studied in the rat. By using the brain-reference method, dose-dependent increases in glucose utilization were clearly shown in all the insulin-sensitive tissues examined. The method seems to be of value for measurement of glucose utilization using radioactive deoxyglucose and positron emission tomography in the heart or other insulin-sensitive tissues, especially during glucose loading. (orig.)

  1. Impact of polymorphisms in WFS1 on prediabetic phenotypes in a population-based sample of middle-aged people with normal and abnormal glucose regulation

    DEFF Research Database (Denmark)

    Sparsø, T; Andersen, G; Albrechtsen, Anders

    2008-01-01

    .025) and decreased 30-min serum insulin levels (p = 0.047) after an oral glucose load. In glucose-tolerant individuals the same allele was associated with increased fasting serum insulin concentration (p = 0.019) and homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.026). To study the complex...... interaction of WFS1 rs734312 on insulin release and insulin resistance we introduced Hotelling's T (2) test. Assuming bivariate normal distribution, we constructed standard error ellipses of the insulinogenic index and HOMA-IR when stratified according to glucose tolerance status around the means of each WFS1...... rs734312 genotype level. The interaction term between individuals with normal glucose tolerance and abnormal glucose regulation on the insulinogenic index and HOMA-IR was significantly associated with the traits (p = 0.0017). CONCLUSIONS/INTERPRETATION: Type 2 diabetes-associated risk alleles of WFS1...

  2. Glucose metabolism in different regions of the rat brain under hypokinetic stress influence

    Science.gov (United States)

    Konitzer, K.; Voigt, S.

    1980-01-01

    Glucose metabolism in rats kept under long term hypokinetic stress was studied in 7 brain regions. Determination was made of the regional levels of glucose, lactate, glutamate, glutamine, aspartate, gamma-aminobutyrate and the incorporation of C-14 from plasma glucose into these metabolites, in glycogen and protein. From the content and activity data the regional glucose flux was approximated quantitatively. Under normal conditions the activity gradient cortex and frontal pole cerebellum, thalamus and mesencephalon, hypothalamus and pons and medulla is identical with that of the regional blood supply (measured with I131 serum albumin as the blood marker). Within the first days of immobilization a functional hypoxia occurred in all brain regions and the utilization of cycle amino acids for protein synthesis was strongly diminished. After the first week of stress the capillary volumes of all regions increased, aerobic glucose metabolism was enhanced (factors 1.3 - 2.0) and the incorporation of glucose C-14 via cycle amino acids into protein was considerably potentiated. The metabolic parameters normalized between the 7th and 11th week of stress. Blood supply and metabolic rate increased most in the hypothalamus.

  3. Evaluation of Brain and Cervical MRI Abnormality Rates in Patients With Systemic Lupus Erythematosus With or Without Neurological Manifestations

    International Nuclear Information System (INIS)

    Harirchian, Mohammad Hossein; Saberi, Hazhir; Najafizadeh, Seyed Reza; Hashemi, Seyed Ali

    2011-01-01

    Central nervous system (CNS) involvement has been observed in 14-80% of patients with systemic lupus erythematosus (SLE). Magnetic resonance imaging (MRI) is an appropriate method for evaluating CNS involvement in these patients. Clinical manifestations and MRI findings of CNS lupus should be differentiated from other mimicking diseases such as multiple sclerosis (MS). The aim of this study was to evaluate the prevalence and extent of brain and cervical cord MRI lesions of lupus patients. The relationship between neurological signs and symptoms and MRI findings were evaluated as well. Fifty SLE patients who had been referred to the rheumatology clinic of our hospital within 2009 were included in a cross sectional study. All patients fulfilled the revised 1981 American College of Rheumatology (ACR) criteria for SLE. We evaluated the neurological signs and symptoms and brain and cervical MRI findings in these patients. Forty-one patients (82%) were female and nine (18%) were male. The mean age was 30.1 ± 9.3 years. Twenty eight (56%) patients had an abnormal brain MRI. No one showed any abnormality in the cervical MRI. The lesions in 20 patients were similar to demyelinative plaques. Seventeen patients with abnormal brain MRI were neurologically asymptomatic. There was only a significant relationship between neurological motor manifestations and brain MRI abnormal findings. Unlike the brain, cervical MRI abnormality and especially asymptomatic cord involvement in MRI is quite rare in SLE patients. This finding may be helpful to differentiate SLE from other CNS disorders such as MS

  4. Resting state brain glucose metabolism is not reduced in normotensive healthy men during aging, after correction for brain atrophy.

    Science.gov (United States)

    Ibáñez, Vicente; Pietrini, Pietro; Furey, Maura L; Alexander, Gene E; Millet, Philippe; Bokde, Arun L W; Teichberg, Diane; Schapiro, Mark B; Horwitz, Barry; Rapoport, Stanley I

    2004-03-15

    Studies using positron emission tomography (PET) have reported that global and regional values for cerebral blood flow and metabolic rates for glucose (CMRglc and rCMRglc) decline with age in humans. We wished to determine if such decreases could have reflected a partial volume effect (PVE) of cerebral atrophy in the elderly, rather than "intrinsic" reductions per gram brain. We used PET to compare rCMRglc, before and after correcting for the PVE, between 13 healthy older men (aged: 55-82 years) and 11 healthy young men (aged: 22-34 years). PET was performed with 18F-fluoro-2-deoxy-d-glucose while the subjects were in the "resting" state (eyes covered and ears plugged with cotton). The PET scans were normalized to a common brain volume after superimposing them on the subjects' tissue segmented magnetic resonance scans. Analysis showed that rCMRglc in the absence of a PVE correction was significantly less in the older group in insular, frontal, superior temporal cortical, and thalamic regions. Statistical significant differences in rCMRglc, however, were absent after the PVE correction. Thus, statistically significant age reductions in regional brain glucose metabolism, corrected for brain atrophy, are not detectable in healthy normotensive men scanned while in the resting state.

  5. mTOR signaling and its roles in normal and abnormal brain development.

    Directory of Open Access Journals (Sweden)

    Nobuyuki eTakei

    2014-04-01

    Full Text Available Target of rapamycin (TOR was first identified in yeast as a target molecule of rapamycin, an anti-fugal and immunosuppressant macrolide compound. In mammals, its orthologue is called mTOR (mammalian TOR. mTOR is a serine/threonine kinase that converges different extracellular stimuli, such as nutrients and growth factors, and diverges into several biochemical reactions, including translation, autophagy, transcription, and lipid synthesis among others. These biochemical reactions govern cell growth and cause cells to attain an anabolic state. Thus, the disruption of mTOR signaling is implicated in a wide array of diseases such as cancer, diabetes, and obesity. In the central nervous system (CNS, the mTOR signaling cascade is activated by nutrients, neurotrophic factors, and neurotransmitters that enhances protein (and possibly lipid synthesis and suppresses autophagy. These processes contribute to normal neuronal growth by promoting their differentiation, neurite elongation and branching, and synaptic formation during development. Therefore, disruption of mTOR signaling may cause neuronal degeneration and abnormal neural development. While reduced mTOR signaling is associated with neurodegeneration, excess activation of mTOR signaling causes abnormal development of neurons and glia, leading to brain malformation. In this review, we first introduce the current state of molecular knowledge of mTOR complexes and signaling in general. We then describe mTOR activation in neurons, which leads to translational enhancement, and finally discuss the link between mTOR and normal/abnormal neuronal growth during development.

  6. Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder.

    Science.gov (United States)

    Noordermeer, Siri D S; Luman, Marjolein; Greven, Corina U; Veroude, Kim; Faraone, Stephen V; Hartman, Catharina A; Hoekstra, Pieter J; Franke, Barbara; Buitelaar, Jan K; Heslenfeld, Dirk J; Oosterlaan, Jaap

    2017-11-01

    Attention-deficit/hyperactivity disorder (ADHD) is associated with structural abnormalities in total gray matter, basal ganglia, and cerebellum. Findings of structural abnormalities in frontal and temporal lobes, amygdala, and insula are less consistent. Remarkably, the impact of comorbid oppositional defiant disorder (ODD) (comorbidity rates up to 60%) on these neuroanatomical differences is scarcely studied, while ODD (in combination with conduct disorder) has been associated with structural abnormalities of the frontal lobe, amygdala, and insula. The aim of this study was to investigate the effect of comorbid ODD on cerebral volume and cortical thickness in ADHD. Three groups, 16 ± 3.5 years of age (mean ± SD; range 7-29 years), were studied on volumetric and cortical thickness characteristics using structural magnetic resonance imaging (surface-based morphometry): ADHD+ODD (n = 67), ADHD-only (n = 243), and control subjects (n = 233). Analyses included the moderators age, gender, IQ, and scan site. ADHD+ODD and ADHD-only showed volumetric reductions in total gray matter and (mainly) frontal brain areas. Stepwise volumetric reductions (ADHD+ODD conduct disorder rather than ODD. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. Assessment of regional glucose metabolism in aging brain and dementia with positron-emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Reivich, M.; Alavi, A.; Ferris, S.; Christman, D.; Fowler, J.; MacGregor, R.; Farkas, T.; Greenberg, J.; Dann, R.; Wolf, A.

    1981-01-01

    This paper explores the alterations in regional glucose metabolism that occur in elderly subjects and those with senile dementia compared to normal young volunteers. Results showed a tendency for the frontal regions to have a lower metabolic rate in patients with dementia although this did not reach the level of significance when compared to the elderly control subjects. The changes in glucose metabolism were symmetrical in both the left and right hemispheres. There was a lack of correlation between the mean cortical metabolic rates for glucose and the global mental function in the patients with senile dementia. This is at variance with most of the regional cerebral blood flow data that has been collected. This may be partly related to the use of substrates other than glucose by the brain in elderly and demented subjects. (PSB)

  8. The nature of white matter abnormalities in blast-related mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Jasmeet P. Hayes

    2015-01-01

    Full Text Available Blast-related traumatic brain injury (TBI has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI. The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC group, and blast-related mTBI with LOC (mTBI + LOC group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1 a region-specific analysis and 2 a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of

  9. Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

    Science.gov (United States)

    Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

    2013-01-01

    Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

  10. Glucose-Coated Gold Nanoparticles Transfer across Human Brain Endothelium and Enter Astrocytes In Vitro

    Science.gov (United States)

    Gromnicova, Radka; Davies, Heather A.; Sreekanthreddy, Peddagangannagari; Romero, Ignacio A.; Lund, Torben; Roitt, Ivan M.; Phillips, James B.; Male, David K.

    2013-01-01

    The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier. PMID:24339894

  11. Glucose-coated gold nanoparticles transfer across human brain endothelium and enter astrocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Radka Gromnicova

    Full Text Available The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier.

  12. Burden and Socio-Behavioral Correlates of Uncontrolled Abnormal Glucose Metabolism in an Urban Population of India.

    Science.gov (United States)

    Mahapatra, Tanmay; Chakraborty, Kaushik; Mahapatra, Sanchita; Mahapatra, Umakanta; Pandey, Naren; Thomson, Peter L; Musk, Arthur W; Mitra, Ramendra N

    2016-01-01

    Progressive burden of diabetes mellitus is a major concern in India. Data on the predictors of poor glycemic control among diabetics are scanty. A population-based cross-sectional study nested in an urban cohort was thus conducted in West Bengal, India to determine the burden and correlates of total and uncontrolled abnormalities in glucose metabolism (AGM) in a representative population. From 9046 adult cohort-members, 269 randomly selected consenting subjects (non-response = 7.24%) were interviewed, examined [blood pressure (BP), anthropometry], tested for fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1C). Those having pre-diagnosed diabetes or FPG ≥126 or HbA1c≥6.5 were defined as diabetic. Among non-diabetics, subjects with FPG (mg/dl) = 100-125 or HbA1C(%) = 5.7-6.4 were defined as pre-diabetic. Pre-diagnosed cases with current FPG ≥126 were defined as uncontrolled AGM. Descriptive and regression analyses were conducted using SAS-9.3.2. Among participants, 28.62% [95% Confidence Interval (95%CI) = 23.19-34.06)] were overweight [body mass index(BMI) = (25-29.99)kg/meter2], 7.81% (4.58-11.03) were obese(BMI≥30kg/meter2), 20.82% (15.93-25.70) were current smokers, 12.64% (8.64-16.64) were current alcohol-drinkers and 46.32% of responders (39.16-53.47) had family history of diabetes. 17.84% (13.24-22.45) had stage-I [140≤average systolic BP (AvSBP in mm of mercury)urban India should include interventions targeting appropriate diabetic control among relatively older persons, unemployed, business-owners, retired, ex-smokers, ex-drinkers and hypertensives.

  13. Impact of newly diagnosed abnormal glucose regulation on long-term prognosis in low risk patients with ST-elevation myocardial infarction: A follow-up study

    Directory of Open Access Journals (Sweden)

    Abdelnoor Michael

    2011-07-01

    Full Text Available Abstract Background Patients with acute myocardial infarction and newly detected abnormal glucose regulation have been shown to have a less favourable prognosis compared to patients with normal glucose regulation. The importance and timing of oral glucose tolerance testing (OGTT in patients with acute myocardial infarction without known diabetes is uncertain. The aim of the present study was to evaluate the impact of abnormal glucose regulation classified by an OGTT in-hospital and at three-month follow-up on clinical outcome in patients with acute ST elevation myocardial infarction (STEMI without known diabetes. Methods Patients (n = 224, age 58 years with a primary percutanous coronary intervention (PCI treated STEMI were followed for clinical events (all-cause mortality, non-fatal myocardial re-infarction, recurrent ischemia causing hospital admission, and stroke. The patients were classified by a standardised 75 g OGTT at two time points, first, at a median time of 16.5 hours after hospital admission, then at three-month follow-up. Based on the OGTT results, the patients were categorised according to the WHO criteria and the term abnormal glucose regulation was defined as the sum of impaired fasting glucose, impaired glucose tolerance and type 2-diabetes. Results The number of patients diagnosed with abnormal glucose regulation in-hospital and at three-month was 105 (47% and 50 (25%, respectively. During the follow up time of (median 33 (27, 39 months, 58 (25.9% patients experienced a new clinical event. There were six deaths, 15 non-fatal re-infarction, 33 recurrent ischemia, and four strokes. Kaplan-Meier analysis of survival free of composite end-points showed similar results in patients with abnormal and normal glucose regulation, both when classified in-hospital (p = 0.4 and re-classified three months later (p = 0.3. Conclusions Patients with a primary PCI treated STEMI, without previously known diabetes, appear to have an excellent

  14. Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

    Science.gov (United States)

    Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

    2016-01-01

    Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

  15. Multidimensional morphometric 3D MRI analyses for detecting brain abnormalities in children: impact of control population.

    Science.gov (United States)

    Wilke, Marko; Rose, Douglas F; Holland, Scott K; Leach, James L

    2014-07-01

    Automated morphometric approaches are used to detect epileptogenic structural abnormalities in 3D MR images in adults, using the variance of a control population to obtain z-score maps in an individual patient. Due to the substantial changes the developing human brain undergoes, performing such analyses in children is challenging. This study investigated six features derived from high-resolution T1 datasets in four groups: normal children (1.5T or 3T data), normal clinical scans (3T data), and patients with structural brain lesions (3T data), with each n = 10. Normative control data were obtained from the NIH study on normal brain development (n = 401). We show that control group size substantially influences the captured variance, directly impacting the patient's z-scores. Interestingly, matching on gender does not seem to be beneficial, which was unexpected. Using data obtained at higher field scanners produces slightly different base rates of suprathreshold voxels, as does using clinically derived normal studies, suggesting a subtle but systematic effect of both factors. Two approaches for controlling suprathreshold voxels in a multidimensional approach (combining features and requiring a minimum cluster size) were shown to be substantial and effective in reducing this number. Finally, specific strengths and limitations of such an approach could be demonstrated in individual cases.

  16. Multicenter Study of Brain Volume Abnormalities in Children and Adolescent-Onset Psychosis

    Science.gov (United States)

    Reig, Santiago; Parellada, Mara; Castro-Fornieles, Josefina; Janssen, Joost; Moreno, Dolores; Baeza, Inmaculada; Bargalló, Nuria; González-Pinto, Ana; Graell, Montserrat; Ortuño, Felipe; Otero, Soraya; Arango, Celso; Desco, Manuel

    2011-01-01

    The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of “schizophrenia” or “other psychosis” showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents. PMID:20478821

  17. Abnormal small-world brain functional networks in obsessive-compulsive disorder patients with poor insight.

    Science.gov (United States)

    Lei, Hui; Cui, Yan; Fan, Jie; Zhang, Xiaocui; Zhong, Mingtian; Yi, Jinyao; Cai, Lin; Yao, Dezhong; Zhu, Xiongzhao

    2017-09-01

    There are limited data on neurobiological correlates of poor insight in obsessive-compulsive disorder (OCD). This study explored whether specific changes occur in small-world network (SWN) properties in the brain functional network of OCD patients with poor insight. Resting-state electroencephalograms (EEGs) were recorded for 12 medication-free OCD patients with poor insight, 50 medication-free OCD patients with good insight, and 36 healthy controls. Both of the OCD groups exhibited topological alterations in the brain functional network characterized by abnormal small-world parameters at the beta band. However, the alterations at the theta band only existed in the OCD patients with poor insight. A relatively small sample size. Subjects were naïve to medications and those with Axis I comorbidity were excluded, perhaps limiting generalizability. Disrupted functional integrity at the beta bands of the brain functional network may be related to OCD, while disrupted functional integrity at the theta band may be associated with poor insight in OCD patients, thus this study might provide novel insight into our understanding of the pathophysiology of OCD. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Regional brain structural abnormality in ischemic stroke patients: a voxel-based morphometry study

    Directory of Open Access Journals (Sweden)

    Ping Wu

    2016-01-01

    Full Text Available Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment (r = -0.609, P = 0.047 and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale (r = -0.737, P = 0.010. Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

  19. Regional brain structural abnormality in ischemic stroke patients: a voxel-based morphometry study.

    Science.gov (United States)

    Wu, Ping; Zhou, Yu-Mei; Zeng, Fang; Li, Zheng-Jie; Luo, Lu; Li, Yong-Xin; Fan, Wei; Qiu, Li-Hua; Qin, Wei; Chen, Lin; Bai, Lin; Nie, Juan; Zhang, San; Xiong, Yan; Bai, Yu; Yin, Can-Xin; Liang, Fan-Rong

    2016-09-01

    Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment ( r = -0.609, P = 0.047) and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale ( r = -0.737, P = 0.010). Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

  20. Detection of glucose in the human brain with1H MRS at 7 Tesla.

    Science.gov (United States)

    Kaiser, Lana G; Hirokazu, Kawaguchi; Fukunaga, Masaki; B Matson, Gerald

    2016-12-01

    A new method is proposed for noninvasive detection of glucose in vivo using proton MR spectroscopy at 7 Tesla. The proposed method utilizes J-difference editing to uncover the resonance of beta-glucose (β-glc) at 3.23 ppm, which is strongly overlapped with choline. Calculations using the density matrix formalism are used to maximize the signal-to-noise ratio of the β-glc resonance at 3.23 ppm. The calculations are verified using phantom and in vivo data collected at 7 Tesla. The proposed method allows observation of the glucose signal at 3.23 ppm in the human brain spectrum. Additional co-edited resonances of N-acetylaspartylglutamatate and glutathione are also detected in the same experiment. The proposed method does not require carbon ( 13 C)- labeled glucose injections and 13 C hardware; as such, it has a potential to provide valuable information on intrinsic glucose concentration in the human brain in vivo. Magn Reson Med 76:1653-1660, 2016. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  1. Glucose metabolism in brain tumor as studied by positron-emission tomography

    International Nuclear Information System (INIS)

    Tsukiyama, Takashi; Tsubokawa, Takashi; Kido, Goro; Kumakawa, Hitoshi; Iio, Masaaki; Hara, Toshihiko.

    1988-01-01

    Although high rates of glycolysis have been correlated with malignancy in glioma on the basis of PET findings using 18-F-deoxyglucose, these results indicate only the activity of hexokinase in the tumor cells; they do not demonstrate what kinds of systems of glycolysis increase. In this report, the differences in the activities of systems of glycolysis on both benign and malignant tumors were studied by means of PET using 11 C-glucose and 11 C-pyruvate administration, along with PET studies of r-CBF, r-OEF and r-CMRO 2 . At a benign glioma, the uptake of 11 C-glucose was lower than in normal brain tissue, with lower r-CBF, r-OEF, and r-CMRO 2 values. Many malignant tumors and cases of meningioma showed increases in glucose uptake with lower oxygen metabolism. On the other hand, the activities of 11 C-pyruvate in both benign and malignant tumors were increased 34 - 131 % relative to normal brain tissue, and there was no difference between benign and malignant tumors. According to these findings, it might be concluded that benign and malignant tumors have mainly an anerobic glycolytic pathway. However, the findings of the alternation of 11 C-glucose uptake suggest that, in addition to the anerobic glycolytic pathway, an alternative metabolic pathway of glucose, such as a pentose-phosphate pathway or an amino-acid-utilizing pathway, may also be present. (author)

  2. Resistance of brain glucose metabolism to thiopental-induced CNS depression in newborn piglets.

    Science.gov (United States)

    Walter, Bernd; Eiselt, Michael; Cumming, Paul; Xiong, Guoming; Hinz, Rainer; Uthe, Susanne; Brust, Peter; Bauer, Reinhard

    2013-05-01

    The transition from mild sedation to deep anaesthesia is marked by the phenomenon of burst suppression (BS). FDG-PET studies show that the cerebral metabolic rate for glucose (CMRglc) declines dramatically with onset of BS in the adult brain. Global CMRglc increases substantially in the post-natal period and achieves its maximum in preadolescence. However, the impact of post-natal brain development on the vulnerability of CMRglc to the onset of BS has not been documented. Therefore, cerebral blood flow and metabolism were measured using a variant of the Kety-Schmidt method, in conjunction with quantitative regional estimation of brain glucose uptake by FDG-PET in groups of neonate and juvenile pigs, under a condition of light sedation or after induction of deep anaesthesia with thiopental. Quantification of simultaneous ECoG recordings was used to establish the correlation between anaesthesia-related changes in brain electrical activity and the observed cerebrometabolic changes. In the condition of light sedation the magnitude of CMRglc was approximately 20% higher in the older pigs, with the greatest developmental increase evident in the cerebral cortex and basal ganglia (Penergy demand of neonate brain during deep anaesthesia represents a reduced part of thiopental suppressing brain metabolism in neonates. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  3. In situ mouse carotid perfusion model: glucose and cholesterol transport in the eye and brain.

    Science.gov (United States)

    Cattelotte, Julie; André, Pascal; Ouellet, Mélissa; Bourasset, Fanchon; Scherrmann, Jean-Michel; Cisternino, Salvatore

    2008-08-01

    The in situ mouse brain perfusion method for measuring blood-brain barrier permeability was adapted to assess transport of solutes at the blood-brain and blood-eye barriers. The procedure was checked with radiolabeled markers in oxygenated bicarbonate-buffered fluid infused for 30 to 120 sec via a carotid artery. Vascular flow estimated with diazepam was 2.2-fold lower in the eye than in the brain. The vascular volume and the integrity markers sucrose and inulin indicated that a perfusion flow rate of 2.5 mL/min preserved the physical integrity of these organs. However, the brain vasculature integrity was more sensitive to acute perfusion pressure than the eye vasculature. The functional capacities of blood barriers were assessed with D-glucose; its transport followed Michaelis-Menten kinetics with an apparent K(m) of 7.6 mmol/L and a V(max) of 23 micromol/sec per g in the brain, and a K(m) of 22.9 mmol/L and a V(max) of 40 micromol/sec per g in the eye. The transport of cholesterol to the brain and eye was significantly enhanced by adding the Abca1 inhibitor probucol, suggesting an Abca1-mediated efflux at the mouse brain and eye blood barriers. Thus in situ carotid perfusion is suitable for elucidating transport processes at the blood-brain and blood-eye barriers.

  4. Brain and cognition abnormalities in long-term anabolic-androgenic steroid users.

    Science.gov (United States)

    Kaufman, Marc J; Janes, Amy C; Hudson, James I; Brennan, Brian P; Kanayama, Gen; Kerrigan, Andrew R; Jensen, J Eric; Pope, Harrison G

    2015-07-01

    Anabolic-androgenic steroid (AAS) use is associated with psychiatric symptoms including increased aggression as well as with cognitive dysfunction. The brain effects of long-term AAS use have not been assessed in humans. This multimodal magnetic resonance imaging study of the brain compared 10 male weightlifters reporting long-term AAS use with 10 age-matched weightlifters reporting no AAS exposure. Participants were administered visuospatial memory tests and underwent neuroimaging. Brain volumetric analyses were performed; resting-state fMRI functional connectivity (rsFC) was evaluated using a region-of-interest analysis focused on the amygdala; and dorsal anterior cingulate cortex (dACC) metabolites were quantified by proton magnetic resonance spectroscopy (MRS). AAS users had larger right amygdala volumes than nonusers (P=0.002) and reduced rsFC between right amygdala and frontal, striatal, limbic, hippocampal, and visual cortical areas. Left amygdala volumes were slightly larger in AAS users (P=0.061) but few group differences were detected in left amygdala rsFC. AAS users also had lower dACC scyllo-inositol levels (P=0.004) and higher glutamine/glutamate ratios (P=0.028), possibly reflecting increased glutamate turnover. On a visuospatial cognitive task, AAS users performed more poorly than nonusers, with the difference approaching significance (P=0.053). Long-term AAS use is associated with right amygdala enlargement and reduced right amygdala rsFC with brain areas involved in cognitive control and spatial memory, which could contribute to the psychiatric effects and cognitive dysfunction associated with AAS use. The MRS abnormalities we detected could reflect enhanced glutamate turnover and increased vulnerability to neurotoxic or neurodegenerative processes, which could contribute to AAS-associated cognitive dysfunction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Brain Abnormalities in Congenital Fibrosis of the Extraocular Muscles Type 1: A Multimodal MRI Imaging Study.

    Directory of Open Access Journals (Sweden)

    Wen Miao

    Full Text Available To explore the possible brain structural and functional alterations in congenital fibrosis of extraocular muscles type 1 (CFEOM1 patients using multimodal MRI imaging.T1-weighted, diffusion tensor images and functional MRI data were obtained from 9 KIF21A positive patients and 19 age- and gender-matched healthy controls. Voxel based morphometry and tract based spatial statistics were applied to the T1-weighted and diffusion tensor images, respectively. Amplitude of low frequency fluctuations and regional homogeneity were used to process the functional MRI data. We then compared these multimodal characteristics between CFEOM1 patients and healthy controls.Compared with healthy controls, CFEOM1 patients demonstrated increased grey matter volume in bilateral frontal orbital cortex and in the right temporal pole. No diffusion indices changes were detected, indicating unaffected white matter microstructure. In addition, from resting state functional MRI data, trend of amplitude of low-frequency fluctuations increases were noted in the right inferior parietal lobe and in the right frontal cortex, and a trend of ReHo increase (p<0.001 uncorrected in the left precentral gyrus, left orbital frontal cortex, temporal pole and cingulate gyrus.CFEOM1 patients had structural and functional changes in grey matter, but the white matter was unaffected. These alterations in the brain may be due to the abnormality of extraocular muscles and their innervating nerves. Future studies should consider the possible correlations between brain morphological/functional findings and clinical data, especially pertaining to eye movements, to obtain more precise answers about the role of brain area changes and their functional consequence in CFEOM1.

  6. Neonatal brain abnormalities associated with autism spectrum disorder in children born very preterm.

    Science.gov (United States)

    Ure, Alexandra M; Treyvaud, Karli; Thompson, Deanne K; Pascoe, Leona; Roberts, Gehan; Lee, Katherine J; Seal, Marc L; Northam, Elisabeth; Cheong, Jeanie L; Hunt, Rod W; Inder, Terrie; Doyle, Lex W; Anderson, Peter J

    2016-05-01

    Very preterm (VP) survivors are at increased risk of autism spectrum disorder (ASD) compared with term-born children. This study explored whether neonatal magnetic resonance (MR) brain features differed in VP children with and without ASD at 7 years. One hundred and seventy-two VP children (brain MR scans at term equivalent age (TEA; 40 weeks' gestation ±2 weeks) and were assessed for ASD at 7 years of age. The presence and severity of white matter, cortical gray matter, deep nuclear gray matter, and cerebellar abnormalities were assessed, and total and regional brain volumes were measured. ASD was diagnosed using a standardized parent report diagnostic interview and confirmed via an independent assessment. Eight VP children (4.7%) were diagnosed with ASD. Children with ASD had more cystic lesions in the cortical white matter at TEA compared with those without ASD (odds ratio [OR] 8.7, 95% confidence interval [CI] 1.5, 51.3, P = 0.02). There was also some evidence for smaller cerebellar volumes in children with ASD compared with those without ASD (OR = 0.82, CI = 0.66, 1.00, P = 0.06). Overall, the results suggest that VP children with ASD have different brain structure in the neonatal period compared with those who do not have ASD. Autism Res 2016, 9: 543-552. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  7. Abnormal connectivity in the sensorimotor network predicts attention deficits in traumatic brain injury.

    Science.gov (United States)

    Shumskaya, Elena; van Gerven, Marcel A J; Norris, David G; Vos, Pieter E; Kessels, Roy P C

    2017-03-01

    The aim of this study was to explore modifications of functional connectivity in multiple resting-state networks (RSNs) after moderate to severe traumatic brain injury (TBI) and evaluate the relationship between functional connectivity patterns and cognitive abnormalities. Forty-three moderate/severe TBI patients and 34 healthy controls (HC) underwent resting-state fMRI. Group ICA was applied to identify RSNs. Between-subject analysis was performed using dual regression. Multiple linear regressions were used to investigate the relationship between abnormal connectivity strength and neuropsychological outcome. Forty (93%) TBI patients showed moderate disability, while 2 (5%) and 1 (2%) upper severe disability and low good recovery, respectively. TBI patients performed worse than HC on the domains attention and language. We found increased connectivity in sensorimotor, visual, default mode (DMN), executive, and cerebellar RSNs after TBI. We demonstrated an effect of connectivity in the sensorimotor RSN on attention (p < 10 -3 ) and a trend towards a significant effect of the DMN connectivity on attention (p = 0.058). A group-by-network interaction on attention was found in the sensorimotor network (p = 0.002). In TBI, attention was positively related to abnormal connectivity within the sensorimotor RSN, while in HC this relation was negative. Our results show altered patterns of functional connectivity after TBI. Attention impairments in TBI were associated with increased connectivity in the sensorimotor network. Further research is needed to test whether attention in TBI patients is directly affected by changes in functional connectivity in the sensorimotor network or whether the effect is actually driven by changes in the DMN.

  8. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    Science.gov (United States)

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  9. Frequency of brain MRI abnormalities in neuromyelitis optica spectrum disorder at presentation: A cohort of Latin American patients.

    Science.gov (United States)

    Carnero Contentti, Edgar; Daccach Marques, Vanessa; Soto de Castillo, Ibis; Tkachuk, Veronica; Antunes Barreira, Amilton; Armas, Elizabeth; Chiganer, Edson; de Aquino Cruz, Camila; Di Pace, José Luis; Hryb, Javier Pablo; Lavigne Moreira, Carolina; Lessa, Carmen; Molina, Omaira; Perassolo, Monica; Soto, Arnoldo; Caride, Alejandro

    2018-01-01

    Brain magnetic resonance imaging (BMRI) lesions were classically not reported in neuromyelitis optica (NMO). However, BMRI lesions are not uncommon in NMO spectrum disorder (NMOSD) patients. To report BMRI characteristic abnormalities (location and configuration) in NMOSD patients at presentation. Medical records and BMRI characteristics of 79 patients with NMOSD (during the first documented attack) in Argentina, Brazil and Venezuela were reviewed retrospectively. BMRI abnormalities were observed in 81.02% of NMOSD patients at presentation. Forty-two patients (53.1%) showed typical-NMOSD abnormalities. We found BMRI abnormalities at presentation in the brainstem/cerebellum (n = 26; 32.9%), optic chiasm (n = 16; 20.2%), area postrema (n = 13; 16.4%), thalamus/hypothalamus (n = 11; 13.9%), corpus callosum (n = 11; 13.9%), periependymal-third ventricle (n = 9; 11.3%), corticospinal tract (n = 7; 8.8%), hemispheric white matter (n = 1; 1.2%) and nonspecific areas (n = 49; 62.03%). Asymptomatic BMRI lesions were more common. The frequency of brain MRI abnormalities did not differ between patients who were positive and negative for aquaporin 4 antibodies at presentation. Typical brain MRI abnormalities are frequent in NMOSD at disease onset. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Differing patterns of brain structural abnormalities between black and white patients with their first episode of psychosis.

    LENUS (Irish Health Repository)

    Morgan, K D

    2010-07-01

    African-Caribbean and black African people living in the UK are reported to have a higher incidence of diagnosed psychosis compared with white British people. It has been argued that this may be a consequence of misdiagnosis. If this is true they might be less likely to show the patterns of structural brain abnormalities reported in white British patients. The aim of this study therefore was to investigate whether there are differences in the prevalence of structural brain abnormalities in white and black first-episode psychosis patients.

  11. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

    1987-01-01

    Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for /sup 82/Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity.

  12. Acute glucose and lactate metabolism are associated with cognitive recovery following traumatic brain injury.

    Science.gov (United States)

    Mannino, Christina; Glenn, Thomas C; Hovda, David A; Vespa, Paul M; McArthur, David L; Van Horn, John D; Wright, Matthew J

    2018-04-01

    Traumatic brain injury (TBI) is associated with acute cerebral metabolic crisis (ACMC). ACMC-related atrophy appears to be prominent in frontal and temporal lobes following moderate-to-severe TBI. This atrophy is correlated with poorer cognitive outcomes in TBI. The current study investigated ability of acute glucose and lactate metabolism to predict long-term recovery of frontal-temporal cognitive function in participants with moderate-to-severe TBI. Cerebral metabolic rate of glucose and lactate were measured by the Kety-Schmidt method on days 0-7 post-injury. Indices of frontal-temporal cognitive processing were calculated for six months post-injury; 12 months post-injury; and recovery (the difference between the six- and 12-month scores). Glucose and lactate metabolism were included in separate regression models, as they were highly intercorrelated. Also, glucose and lactate values were centered and averaged and included in a final regression model. Models for the prediction frontal-temporal cognition at six and 12 months post-injury were not significant. However, average glucose and lactate metabolism predicted recovery of frontal-temporal cognition, accounting for 23% and 22% of the variance, respectively. Also, maximum glucose metabolism, but not maximum lactate metabolism, was an inverse predictor in the recovery of frontal-temporal cognition, accounting for 23% of the variance. Finally, the average of glucose and lactate metabolism predicted frontal-temporal cognitive recovery, accounting for 22% of the variance. These data indicate that acute glucose and lactate metabolism both support cognitive recovery from TBI. Also, our data suggest that control of endogenous fuels and/or supplementation with exogenous fuels may have therapeutic potential for cognitive recovery from TBI. © 2017 Wiley Periodicals, Inc.

  13. The metabolic trinity, glucose-glycogen-lactate, links astrocytes and neurons in brain energetics, signaling, memory, and gene expression.

    Science.gov (United States)

    Dienel, Gerald A

    2017-01-10

    Glucose, glycogen, and lactate are traditionally identified with brain energetics, ATP turnover, and pathophysiology. However, recent studies extend their roles to include involvement in astrocytic signaling, memory consolidation, and gene expression. Emerging roles for these brain fuels and a readily-diffusible by-product are linked to differential fluxes in glycolytic and oxidative pathways, astrocytic glycogen dynamics, redox shifts, neuron-astrocyte interactions, and regulation of astrocytic activities by noradrenaline released from the locus coeruleus. Disproportionate utilization of carbohydrate compared with oxygen during brain activation is influenced by catecholamines, but its physiological basis is not understood and its magnitude may be affected by technical aspects of metabolite assays. Memory consolidation and gene expression are impaired by glycogenolysis blockade, and prevention of these deficits by injection of abnormally-high concentrations of lactate was interpreted as a requirement for astrocyte-to-neuron lactate shuttling in memory and gene expression. However, lactate transport was not measured and evidence for presumed shuttling is not compelling. In fact, high levels of lactate used to preserve memory consolidation and induce gene expression are sufficient to shut down neuronal firing via the HCAR1 receptor. In contrast, low lactate levels activate a receptor in locus coeruleus that stimulates noradrenaline release that may activate astrocytes throughout brain. Physiological relevance of exogenous concentrations of lactate used to mimic and evaluate metabolic, molecular, and behavioral effects of lactate requires close correspondence with the normal lactate levels, the biochemical and cellular sources and sinks, and specificity of lactate delivery to target cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu Shengjie [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Chemaitilly, Wassim [Division of Endocrinology, Department of Pediatric Medicine, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Lukose, Renin C.; Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2012-11-15

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  15. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    International Nuclear Information System (INIS)

    Hua Chiaho; Wu Shengjie; Chemaitilly, Wassim; Lukose, Renin C.; Merchant, Thomas E.

    2012-01-01

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test ≥7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  16. Abnormal autonomic and associated brain activities during rest in autism spectrum disorder

    Science.gov (United States)

    Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T.; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R.

    2014-01-01

    Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916

  17. Study of cerebral metabolism of glucose in normal human brain correlated with age

    International Nuclear Information System (INIS)

    Si, M.

    2007-01-01

    Full text: The objective was to determine whether cerebral metabolism in various regions of the brain differs with advancing age by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They (with the age ranging from 21 to 88; mean age+/-SD: 49.77+/-13.51) were selected with: (i)absence of clear focal brain lesions (epilepsy.cerebrovascular diseases etc);(ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes;(iii) absence of psychiatric disorders and abuse of drugs and alcohol. They were sub grouped into six groups with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose were matched. All subgroups were compared to the control group of 31-40 years old (84 samples; mean age+/-SD: 37.15+/-2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later, their brains were scanned for 10min. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2) .The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three-dimensional localized by MNI Space utility (MSU) software. Results:Relative hypometabolic brain areas detected are mainly in the cortical structures such as bilateral prefrontal cortex, superior temporal gyrus(BA22), parietal cortex (inferior parietal lobule and precuneus(BA40, insula(BA13)), parahippocampal gyrus and amygdala (p<0.01).It is especially apparent in the prefrontal cortex (BA9)and sensory-motor cortex(BA5, 7) (p<0.001), while basal ganglia and cerebellum remained metabolically unchanged with advancing age. Conclusions Regional cerebral metabolism of glucose shows a descent tendency with aging, especially in the prefrontal cortex (BA9)and

  18. Dynamic brain glucose metabolism identifies anti-correlated cortical-cerebellar networks at rest.

    Science.gov (United States)

    Tomasi, Dardo G; Shokri-Kojori, Ehsan; Wiers, Corinde E; Kim, Sunny W; Demiral, Şukru B; Cabrera, Elizabeth A; Lindgren, Elsa; Miller, Gregg; Wang, Gene-Jack; Volkow, Nora D

    2017-12-01

    It remains unclear whether resting state functional magnetic resonance imaging (rfMRI) networks are associated with underlying synchrony in energy demand, as measured by dynamic 2-deoxy-2-[ 18 F]fluoroglucose (FDG) positron emission tomography (PET). We measured absolute glucose metabolism, temporal metabolic connectivity (t-MC) and rfMRI patterns in 53 healthy participants at rest. Twenty-two rfMRI networks emerged from group independent component analysis (gICA). In contrast, only two anti-correlated t-MC emerged from FDG-PET time series using gICA or seed-voxel correlations; one included frontal, parietal and temporal cortices, the other included the cerebellum and medial temporal regions. Whereas cerebellum, thalamus, globus pallidus and calcarine cortex arose as the strongest t-MC hubs, the precuneus and visual cortex arose as the strongest rfMRI hubs. The strength of the t-MC linearly increased with the metabolic rate of glucose suggesting that t-MC measures are strongly associated with the energy demand of the brain tissue, and could reflect regional differences in glucose metabolism, counterbalanced metabolic network demand, and/or differential time-varying delivery of FDG. The mismatch between metabolic and functional connectivity patterns computed as a function of time could reflect differences in the temporal characteristics of glucose metabolism as measured with PET-FDG and brain activation as measured with rfMRI.

  19. Brain volumetric abnormalities in patients with anorexia and bulimia nervosa: a voxel-based morphometry study.

    Science.gov (United States)

    Amianto, Federico; Caroppo, Paola; D'Agata, Federico; Spalatro, Angela; Lavagnino, Luca; Caglio, Marcella; Righi, Dorico; Bergui, Mauro; Abbate-Daga, Giovanni; Rigardetto, Roberto; Mortara, Paolo; Fassino, Secondo

    2013-09-30

    Recent studies focussing on neuroimaging features of eating disorders have observed that anorexia nervosa (AN) is characterized by significant grey matter (GM) atrophy in many brain regions, especially in the cerebellum and anterior cingulate cortex. To date, no studies have found GM atrophy in bulimia nervosa (BN) or have directly compared patients with AN and BN. We used voxel-based morphometry (VBM) to characterize brain abnormalities in AN and BN patients, comparing them with each other and with a control group, and correlating brain volume with clinical features. We recruited 17 AN, 13 BN and 14 healthy controls. All subjects underwent high-resolution magnetic resonance imaging (MRI) with a T1-weighted 3D image. VBM analysis was carried out with the FSL-VBM 4.1 tool. We found no global atrophy, but regional GM reduction in AN with respect to controls and BN in the cerebellum, fusiform area, supplementary motor area, and occipital cortex, and in the caudate in BN compared to AN and controls. Both groups of patients had a volumetric increase bilaterally in somatosensory regions with respect to controls, in areas that are typically involved in the sensory-motor integration of body stimuli and in mental representation of the body image. Our VBM study documented, for the first time in BN patients, the presence of volumetric alterations and replicated previous findings in AN patients. We evidenced morphological differences between AN and BN, demonstrating in the latter atrophy of the caudate nucleus, a region involved in reward mechanisms and processes of self-regulation, perhaps involved in the genesis of the binge-eating behaviors of this disorder. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Factors associated with screening for glucose abnormalities after gestational diabetes mellitus: baseline cohort of the interventional IMPACT study.

    Science.gov (United States)

    Bihan, H; Cosson, E; Khiter, C; Vittaz, L; Faghfouri, F; Leboeuf, D; Carbillon, L; Dauphin, H; Reach, G; Valensi, P

    2014-04-01

    Although it is important to screen women who have had gestational diabetes mellitus (GDM) for abnormal post-partum glucose levels, such testing is rarely performed. The aim of this study was to use data from the first observational phase of the IMPACT study to determine rates of screening within 6 months of delivery in a multiethnic cohort, focusing in particular on the effects of social deprivation and the risk of future diabetes. To investigate the frequency of post-partum screening, charts were analyzed, and all women attending four centres located in a deprived area who had had GDM between January 2009 and December 2010 were contacted by phone. The Evaluation of Precarity and Inequalities in Health Examination Centres (EPICES) deprivation index and Finnish Diabetes Risk Score (FINDRISK) questionnaire were also evaluated. Data were evaluable for 589 of the 719 women contacted (mean age: 33.4 ± 5.2 years; mean body mass index: 27.6 ± 5.4 kg/m(2)), and 196 (33.3%) reported having been screened. On multivariate analysis, factors associated with a lack of screening were smoking [odds ratio (OR): 0.42 (0.20-0.90), P<0.05], low consumption of fruit and vegetables [OR: 0.58 (0.39-0.82), P<0.01] and heavier offspring birth weight (P<0.05), although there were no differences in FINDRISK and EPICES scores between screened and unscreened women. One-third of women who had had GDM reported having been screened for dysglycaemia at 6 months post-partum. However, it is expected that the interventional phase of the IMPACT study will increase screening rates, especially in women with the risk factors associated with lower screening rates during this observational phase. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Added value of fetal MRI in fetuses with suspected brain abnormalities on neurosonography: a systematic review and meta-analysis

    NARCIS (Netherlands)

    van Doorn, Martine; Oude Rengerink, Katrien; Newsum, Esther A.; Reneman, Liesbeth; Majoie, Charles B.; Pajkrt, Eva

    2016-01-01

    To evaluate the additional diagnostic value of fetal Magnetic Resonance Imaging (MRI) in fetuses with suspected brain abnormalities identified with advanced neurosonography (NS). A systematic literature search was performed for studies reporting on a comparison between diagnosis with NS and MRI, in

  2. Cross-Sectional and Longitudinal Abnormalities in Brain Structure in Children with Severe Mood Dysregulation or Bipolar Disorder

    Science.gov (United States)

    Adleman, Nancy E.; Fromm, Stephen J.; Razdan, Varun; Kayser, Reilly; Dickstein, Daniel P.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen

    2012-01-01

    Background: There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in BD have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time.…

  3. Mutation in mitochondrial ribosomal protein MRPS22 leads to Cornelia de Lange-like phenotype, brain abnormalities and hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    Smits, P.; Saada, A.; Wortmann, S.B.; Heister, A.; Brink, M.; Pfundt, R.P.; Miller, C.; Haas, D.; Hantschmann, R.; Rodenburg, R.J.T.; Smeitink, J.A.M.; Heuvel, L.P.W.J. van den

    2011-01-01

    The oxidative phosphorylation (OXPHOS) system is under control of both the mitochondrial and the nuclear genomes; 13 subunits are synthesized by the mitochondrial translation machinery. We report a patient with Cornelia de Lange-like dysmorphic features, brain abnormalities and hypertrophic

  4. Detection of glycemic abnormalities in adolescents with beta thalassemia using continuous glucose monitoring and oral glucose tolerance in adolescents and young adults with β-thalassemia major: Pilot study

    Directory of Open Access Journals (Sweden)

    Ashraf T Soliman

    2013-01-01

    Full Text Available Background: Both insulin deficiency and resistance are reported in patients with β-thalassemia major (BTM. The use of continuous blood glucose monitoring (CGM, among the different methods for early detection of glycemic abnormalities, has not been studied thoroughly in these adolescents. Materials and Methods: To assess the oralglucose tolerance (OGT and 72-h continuous glucose concentration by the continuous glucose monitoring system (CGMS and calculate homeostatic model assessment (HOMA, and the quantitative insulin sensitivity check index (QUICKI was conducted in 16 adolescents with BTM who were receiving regular blood transfusions every 2-4 weeks and iron-chelation therapy since early childhood. Results: Sixteen adolescents with BTM (age: 19.75 ± 3 years were investigated. Using OGTT, (25% had impaired fasting blood (plasma glucose concentration (BG (>5.6 mmol/L. 2-h after the glucose load, one of them had BG = 16.2 mmol/L (diabetic and two had impaired glucose tolerance (IGT (BG > 7.8 and 11.1 mmol/L and 9 with IGT (56%. HOMA and QUICKI revealed levels 0.33 (0.36 ± 0.03, respectively, ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the β-cell function (B% on one hand and the fasting and the 2-h BG (r=−0.6, and − 0.48, P < 0.01, respectively on the other hand. Neither fasting serum insulin nor c-peptide concentrations were correlated with fasting BG or ferritin levels. The average and maximum blood glucose levels during CGM were significantly correlated with the fasting BG (r = 0.68 and 0.39, respectively, with P < 0.01 and with the BG at 2-hour after oral glucose intake (r = 0.87 and 0.86 respectively, with P < 0.001. Ferritin concentrations were correlated with the fasting BG and the 2-h blood glucose levels in the OGTT (r = 0.52, and r = 0.43, respectively, P < 0.01 as well as with the average BG recorded by CGM (r = 0.75, P < 0.01. Conclusion: CGM has proven to

  5. Clinical significance of brain SPECT abnormalities of thalami and cerebellum in cerebral palsy with normal MRI

    Energy Technology Data Exchange (ETDEWEB)

    Park, C. H.; Lim, S. Y.; Lee, I. Y.; Kim, O. H.; Bai, M. S.; Kim, S. J.; Yoon, S. N.; Cho, C. W. [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    1997-07-01

    The cerebral palsy(CP) encephalopathies are often of uncertain etiology and various functional image findings comparing with anatomical image findings have been reported. However, only a few have mentioned its clinical implications. The purpose of our report is to compare clinical severity and functional SPECT abnormalities of thalami and cerebellum in CP patients with normal MRI. Thirty six CP patients with bilateral spastic palsy who had normal MRI and brain SPECT were studied from July 1996 to September 1997. The patients' age at the time of SPECT was 22.84{+-}17.69 months. The patients were divided into two groups according to motor quotient(MQ); moderate defect (>50MQ : n=27 MQ=22.78{+-}10.36), mild defect (<50MQ : n=9, MQ=66.11{+-}13.87). The degree of rCBF decrease between the two groups was evaluated by {chi}{sup 2} test. Brain SPECT was performed following IV administration of 0.05-0.1 mCi/kg (minimum 2.0 mCi) of Tc-99m ECD and chloral hydrate sedation (50-80 mg/kg p.o) using a triple head system (MS 3, Siemens). Interpretation of brain SPECT was visual analysis: severe decrease is defined when the defect is moderate to marked and mild decrease in rCBF as mild. Seven of 36 (19.4%) showed unilateral or bilateral moderate decrease in rCBF in thalami, 20(55.6%) showed mild decrease, and 9(25.0%) showed no decreased rCBF. All 7 who had moderate thalamic defect reveled moderate motor defect clinically. Ten of 36(27.9%) revealed unilateral or bilateral moderate rCBF defect, 23 (63.9%) depicted mild defect, and 3(8.3%) showed no defect. Sixteen with moderate thalamic rCBF defect showed moderate motor defect in 15 patients. There was statistically significant (p=0.02605) relationship between rCBF defect and motor defect in our CP patients. In conclusion, brain SPECT appears sensitive, non-invasive tool in the evaluation as well as in the prognostication of bilateral spastic cerebral palsy patients and deserves further study using larger number of patients.

  6. A survey of obesity and abnormal glucose tolerance in first degree relatives of women with polycystic ovarian syndrome referred to gynaecology clinics of Shiraz university of medical sciences

    Directory of Open Access Journals (Sweden)

    marziye Akbarzadeh

    2011-03-01

    Full Text Available Polycystic ovarian (pco syndrome is one of the most prevalent( 4-8% endocrine glands disorders among premenopause women. Polycystic ovary syndrome as a form of functional ovarian hyperandrogenemia may has characteristics such as choronic anovulation, infertility, abnormal menstruation and android obesity. This diseas has genetic aspect and in different studies similar abnormalities have been seen in their first degree relatives. Materials and Methods: This research is a case-control study carried out on 107 individuals as case group and 107 individuals as control group selected by simple random sampling in 2009. After recognition patients with PCO syndrome , their first degree relatives (Father,mother,sister and brother have been interviewed. BMI and WHR indices of the both blood samples were taken to study their serum glucose tolerance. Results: Case group, from view point of obesity (BMI≥30 and centeral obesity , ITG level and diabetes regarding WHO standards was higher than similar individuals in control group,but this difference was not statistically significant . The mean of fasting blood sugar in fathers , mothers , brothers and sisters of cas group was significantly higher (p=0.001. Regarding Chi-square test there was no significant relation between obesity diabetes in the both groups. , (BMI≥30kg/m2, centeral obesity and lack of impaired glucose tolerance and type2 diabetes in the both groups. Conclusion: The first degree relatives of the women suffering from polycystic ovarian syndrome are exposed to abnormal glucose tolerance and android obesity.

  7. Maternal insulin sensitivity is associated with oral glucose-induced changes in fetal brain activity.

    Science.gov (United States)

    Linder, Katarzyna; Schleger, Franziska; Ketterer, Caroline; Fritsche, Louise; Kiefer-Schmidt, Isabelle; Hennige, Anita; Häring, Hans-Ulrich; Preissl, Hubert; Fritsche, Andreas

    2014-06-01

    Fetal programming plays an important role in the pathogenesis of type 2 diabetes. The aim of the present study was to investigate whether maternal metabolic changes during OGTT influence fetal brain activity. Thirteen healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was determined by glucose and insulin measurements at 0, 60 and 120 min. At each time point, fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device and response latencies were determined. Maternal insulin increased from a fasting level of 67 ± 25 pmol/l (mean ± SD) to 918 ± 492 pmol/l 60 min after glucose ingestion and glucose levels increased from 4.4 ± 0.3 to 7.4 ± 1.1 mmol/l. Over the same time period, fetal response latencies decreased from 297 ± 99 to 235 ± 84 ms (p = 0.01) and then remained stable until 120 min (235 ± 84 vs 251 ± 91 ms, p = 0.39). There was a negative correlation between maternal insulin sensitivity and fetal response latencies 60 min after glucose ingestion (r = 0.68, p = 0.02). After a median split of the group based on maternal insulin sensitivity, fetuses of insulin-resistant mothers showed a slower response to auditory stimuli (283 ± 79 ms) than those of insulin-sensitive mothers (178 ± 46 ms, p = 0.03). Lower maternal insulin sensitivity is associated with slower fetal brain responses. These findings provide the first evidence of a direct effect of maternal metabolism on fetal brain activity and suggest that central insulin resistance may be programmed during fetal development.

  8. Abnormal Spontaneous Brain Activity in Patients With Anisometropic Amblyopia Using Resting-State Functional Magnetic Resonance Imaging.

    Science.gov (United States)

    Tang, Angcang; Chen, Taolin; Zhang, Junran; Gong, Qiyong; Liu, Longqian

    2017-09-01

    To explore the abnormality of spontaneous activity in patients with anisometropic amblyopia under resting-state functional magnetic resonance imaging (Rs-fMRI). Twenty-four participants were split into two groups. The anisometropic amblyopia group had 10 patients, all of whom had anisometropic amblyopia of the right eye, and the control group had 14 healthy subjects. All participants underwent Rs-fMRI scanning. Measurement of amplitude of low frequency fluctuations of the brain, which is a measure of the amplitudes of spontaneous brain activity, was used to investigate brain changes between the anisometropic amblyopia and control groups. Compared with an age- and gender-matched control group, the anisometropic amblyopia group showed increased amplitude of low frequency fluctuations of spontaneous brain activity in the left superior temporal gyrus, the left inferior parietal lobe, the left pons, and the right inferior semi-lunar lobe. The anisometropic amblyopia group also showed decreased amplitude of low frequency fluctuations in the bilateral medial frontal gyrus. This study demonstrated abnormal spontaneous brain activities in patients with anisometropic amblyopia under Rs-fMRI, and these abnormalities might contribute to the neuropathological mechanisms of anisometropic amblyopia. [J Pediatr Ophthalmol Strabismus. 2017;54(5):303-310.]. Copyright 2017, SLACK Incorporated.

  9. Abnormal subcortical brain morphology in patients with knee osteoarthritis: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Cui Ping eMao

    2016-01-01

    Full Text Available Despite the involvement of subcortical brain structures in the pathogenesis of chronic pain and persistent pain as the defining symptom of knee osteoarthritis (KOA, little attention has been paid to the morphometric measurements of these subcortical nuclei in patients with KOA. The purpose of this study is to explore the potential morphological abnormalities of subcortical brain structures in patients with KOA as compared to healthy control subjects by using high resolution MRI. Structural MRI data were acquired from 26 patients with KOA and 31 demographically similar healthy individuals. The MR data were analyzed by using FMRIB's integrated registration and segmentation tool (FIRST. Both volumetric analysis and surface-based shape analysis were performed to characterize the subcortical morphology. The normalized volumes of bilateral caudate nucleus were significantly smaller in the KOA group than in the control group (P = 0.004. There was also a trend toward smaller volume of the hippocampus in KOA as compared to the control group (P = 0.027. Detailed surface analyses further localized these differences with a greater involvement of the left hemisphere (P < 0.05, corrected for the caudate nucleus. Hemispheric asymmetry (right larger than left of the caudate nucleus was found in both KOA and control groups. Besides, no significant correlation was found between the structural data and pain intensities. Our results indicated that patients with KOA had statistically significant smaller normalized volumes of bilateral caudate nucleus and a trend toward smaller volume of the hippocampus as compared to the control subjects. Further investigations are necessary to characterize the role of caudate nucleus in the course of chronicity of pain associated with KOA.

  10. Disrupted nodal and hub organization account for brain network abnormalities in Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Yuko Koshimori

    2016-11-01

    Full Text Available The recent application of graph theory to brain networks promises to shed light on complex diseases such as Parkinson’s disease. This study aimed to investigate functional changes in sensorimotor and cognitive networks in parkinsonian patients, with a focus on inter- and intra-connectivity organization in the disease-associated nodal and hub regions using the graph theoretical analyses. Resting-state functional MRI data of a total of 65 participants, including 23 healthy controls and 42 patients, were investigated in 120 nodes for local efficiency, betweenness centrality, and degree. Hub regions were identified in the healthy control and patient groups. We found nodal and hub changes in patients compared with healthy controls, including the right pre-supplementary motor area, left anterior insula, bilateral mid-insula, bilateral dorsolateral prefrontal cortex, and right caudate nucleus. In general, nodal regions within the sensorimotor network (i.e. right pre-supplementary motor area and right mid-insula displayed weakened connectivity, with the former node associated with more severe bradykinesia, and impaired integration with default mode network regions. The left mid-insula also lost its hub properties in patients. Within the executive networks, the left anterior insular cortex lost its hub properties in patients, while a new hub region was identified in the right caudate nucleus, paralleled by an increased level of inter- and intra-connectivity in the bilateral dorsolateral prefrontal cortex possibly representing compensatory mechanisms. These findings highlight the diffuse changes in nodal organization and regional hub disruption accounting for the distributed abnormalities across brain networks and the clinical manifestations of Parkinson’s disease.

  11. Steady-state brain glucose transport kinetics re-evaluated with a four-state conformational model

    Directory of Open Access Journals (Sweden)

    João M N Duarte

    2009-10-01

    Full Text Available Glucose supply from blood to brain occurs through facilitative transporter proteins. A near linear relation between brain and plasma glucose has been experimentally determined and described by a reversible model of enzyme kinetics. A conformational four-state exchange model accounting for trans-acceleration and asymmetry of the carrier was included in a recently developed multi-compartmental model of glucose transport. Based on this model, we demonstrate that brain glucose (Gbrain as function of plasma glucose (Gplasma can be described by a single analytical equation namely comprising three kinetic compartments: blood, endothelial cells and brain. Transport was described by four parameters: apparent half saturation constant Kt, apparent maximum rate constant Tmax, glucose consumption rate CMRglc, and the iso-inhibition constant Kii that suggests Gbrain as inhibitor of the isomerisation of the unloaded carrier. Previous published data, where Gbrain was quantified as a function of plasma glucose by either biochemical methods or NMR spectroscopy, were used to determine the aforementioned kinetic parameters. Glucose transport was characterized by Kt ranging from 1.5 to 3.5 mM, Tmax/CMRglc from 4.6 to 5.6, and Kii from 51 to 149 mM. It was noteworthy that Kt was on the order of a few mM, as previously determined from the reversible model. The conformational four-state exchange model of glucose transport into the brain includes both efflux and transport inhibition by Gbrain, predicting that Gbrain eventually approaches a maximum concentration. However, since Kii largely exceeds Gplasma, iso-inhibition is unlikely to be of substantial importance for plasma glucose below 25 mM. As a consequence, the reversible model can account for most experimental observations under euglycaemia and moderate cases of hypo- and hyperglycaemia.

  12. Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

    Science.gov (United States)

    Altmann, Andre; Botía, Juan A; Jahanshad, Neda; Hibar, Derrek P; Absil, Julie; Alhusaini, Saud; Alvim, Marina K M; Auvinen, Pia; Bartolini, Emanuele; Bergo, Felipe P G; Bernardes, Tauana; Blackmon, Karen; Braga, Barbara; Caligiuri, Maria Eugenia; Calvo, Anna; Carr, Sarah J; Chen, Jian; Chen, Shuai; Cherubini, Andrea; David, Philippe; Domin, Martin; Foley, Sonya; França, Wendy; Haaker, Gerrit; Isaev, Dmitry; Keller, Simon S; Kotikalapudi, Raviteja; Kowalczyk, Magdalena A; Kuzniecky, Ruben; Langner, Soenke; Lenge, Matteo; Leyden, Kelly M; Liu, Min; Loi, Richard Q; Martin, Pascal; Mascalchi, Mario; Morita, Marcia E; Pariente, Jose C; Rodríguez-Cruces, Raul; Rummel, Christian; Saavalainen, Taavi; Semmelroch, Mira K; Severino, Mariasavina; Thomas, Rhys H; Tondelli, Manuela; Tortora, Domenico; Vaudano, Anna Elisabetta; Vivash, Lucy; von Podewils, Felix; Wagner, Jan; Weber, Bernd; Yao, Yi; Yasuda, Clarissa L; Zhang, Guohao; Bargalló, Nuria; Bender, Benjamin; Bernasconi, Neda; Bernasconi, Andrea; Bernhardt, Boris C; Blümcke, Ingmar; Carlson, Chad; Cavalleri, Gianpiero L; Cendes, Fernando; Concha, Luis; Delanty, Norman; Depondt, Chantal; Devinsky, Orrin; Doherty, Colin P; Focke, Niels K; Gambardella, Antonio; Guerrini, Renzo; Hamandi, Khalid; Jackson, Graeme D; Kälviäinen, Reetta; Kochunov, Peter; Kwan, Patrick; Labate, Angelo; McDonald, Carrie R; Meletti, Stefano; O'Brien, Terence J; Ourselin, Sebastien; Richardson, Mark P; Striano, Pasquale; Thesen, Thomas; Wiest, Roland; Zhang, Junsong; Vezzani, Annamaria; Ryten, Mina; Thompson, Paul M

    2018-01-01

    opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = −0.27 to −0.51; P < 1.49 × 10−4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < −0.0018; P < 1.49 × 10−4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed. PMID:29365066

  13. Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation for advanced Parkinson's disease.

    Science.gov (United States)

    Volonté, M A; Garibotto, V; Spagnolo, F; Panzacchi, A; Picozzi, P; Franzin, A; Giovannini, E; Leocani, L; Cursi, M; Comi, G; Perani, D

    2012-07-01

    Despite its large clinical application, our understanding about the mechanisms of action of deep brain stimulation of the subthalamic nucleus is still limited. Aim of the present study was to explore cortical and subcortical metabolic modulations measured by Positron Emission Tomography associated with improved motor manifestations after deep brain stimulation in Parkinson disease, comparing the ON and OFF conditions. Investigations were performed in the stimulator off- and on-conditions in 14 parkinsonian patients and results were compared with a group of matched healthy controls. The results were also used to correlate metabolic changes with the clinical effectiveness of the procedure. The comparisons using Statistical parametric mapping revealed a brain metabolic pattern typical of advanced Parkinson disease. The direct comparison in ON vs OFF condition showed mainly an increased metabolism in subthalamic regions, corresponding to the deep brain stimulation site. A positive correlation exists between neurostimulation clinical effectiveness and metabolic differences in ON and OFF state, including the primary sensorimotor, premotor and parietal cortices, anterior cingulate cortex. Deep brain stimulation seems to operate modulating the neuronal network rather than merely exciting or inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal features suggest that the improvement of specific motor signs associated with deep brain stimulation might be explained by the functional modulation, not only in the target region, but also in surrounding and remote connecting areas, resulting in clinically beneficial effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Burden and Socio-Behavioral Correlates of Uncontrolled Abnormal Glucose Metabolism in an Urban Population of India.

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    Tanmay Mahapatra

    Full Text Available Progressive burden of diabetes mellitus is a major concern in India. Data on the predictors of poor glycemic control among diabetics are scanty. A population-based cross-sectional study nested in an urban cohort was thus conducted in West Bengal, India to determine the burden and correlates of total and uncontrolled abnormalities in glucose metabolism (AGM in a representative population.From 9046 adult cohort-members, 269 randomly selected consenting subjects (non-response = 7.24% were interviewed, examined [blood pressure (BP, anthropometry], tested for fasting plasma glucose (FPG and glycosylated hemoglobin (HbA1C. Those having pre-diagnosed diabetes or FPG ≥126 or HbA1c≥6.5 were defined as diabetic. Among non-diabetics, subjects with FPG (mg/dl = 100-125 or HbA1C(% = 5.7-6.4 were defined as pre-diabetic. Pre-diagnosed cases with current FPG ≥126 were defined as uncontrolled AGM. Descriptive and regression analyses were conducted using SAS-9.3.2.Among participants, 28.62% [95% Confidence Interval (95%CI = 23.19-34.06] were overweight [body mass index(BMI = (25-29.99kg/meter2], 7.81% (4.58-11.03 were obese(BMI≥30kg/meter2, 20.82% (15.93-25.70 were current smokers, 12.64% (8.64-16.64 were current alcohol-drinkers and 46.32% of responders (39.16-53.47 had family history of diabetes. 17.84% (13.24-22.45 had stage-I [140≤average systolic BP (AvSBP in mm of mercury<160 or 90≤average diastolic BP (AvDBP<100] and 12.64% (8.64-16.64 had stage-II (AvSBP≥160 or AvDBP≥160 hypertension. Based on FPG and HbA1c, 10.41% (6.74-14.08 were diabetic and 27.88% (22.49-33.27 were pre-diabetic. Overall prevalence of diabetes was 15.61% (11.25-19.98. Among pre-diagnosed cases, 46.43% (26.74-66.12 had uncontrolled AGM. With one year increase in age [Odds Ratio(OR = 1.05(1.03-1.07], retired subjects [OR = 9.14(1.72-48.66], overweight[OR = 2.78(1.37-5.64], ex-drinkers [OR = 4.66(1.35-16.12] and hypertensives [ORStage I = 3.75(1.42-9.94; ORStage II = 4

  15. Abnormal serotonin transporter availability in the brains of adults with conduct disorder.

    Science.gov (United States)

    Chang, Chieh; Gau, Susan Shur-Fen; Huang, Wen-Sheng; Shiue, Chyng-Yann; Yeh, Chin-Bin

    2017-06-01

    The aims of the current study were to determine whether patients with conduct disorder (CD) showed an abnormal availability of serotonin reuptake transporter (SERT), and if their hyperkinetic symptoms, impulsivity, and quality of life were correlated with the availability of SERT. We recruited 14 drug-naïve patients with CD and eight age-matched healthy controls (HCs). The adult attention-deficit/hyperactivity disorder (ADHD) self-report scale (ASRS), Barrett impulsivity scale (BIS), and the World Health Organization quality of life-brief version (WHOQOL-BREF) scale were administered. Positron emission tomography (PET) of the brain with 4-[ 18 F]-ADAM was arranged for SERT imaging. SERT availability was significantly reduced in the striatum and midbrain of patients with CD. Quality of life and inattention symptoms were also significantly correlated with the availability of SERT in the prefrontal cortex. The study suggested that a reduction in the availability of SERT might be associated with CD and could potentially predict poor quality of life or symptoms of inattention for these patients. The implications of our results might be limited to individuals with CD; a future study with a larger sample to validate our preliminary results is warranted. Copyright © 2016. Published by Elsevier B.V.

  16. Structural brain abnormalities in patients with type I bipolar disorder and suicidal behavior.

    Science.gov (United States)

    Duarte, Dante G G; Neves, Maila de Castro L; Albuquerque, Maicon R; Turecki, Gustavo; Ding, Yang; de Souza-Duran, Fabio Luis; Busatto, Geraldo; Correa, Humberto

    2017-07-30

    Some studies have identified brain morphological changes in the frontolimbic network (FLN) in bipolar subjects who attempt suicide (SA). The present study investigated neuroanatomical abnormalities in the FLN to find a possible neural signature for suicidal behavior in patients with bipolar disorder type I (BD-I). We used voxel-based morphometry to compare euthymic patients with BD-I who had attempted suicide (n=20), who had not attempted suicide (n=19) and healthy controls (HCs) (n=20). We also assessed the highest medical lethality of their previous SA. Compared to the participants who had not attempted suicide, the patients with BD-I who had attempted suicide exhibited significantly increased gray matter volume (GMV) in the right rostral anterior cingulate cortex (ACC), which was more pronounced and extended further to the left ACC in the high-lethality subgroup (p<0.05, with family-wise error (FWE) correction for multiple comparisons using small-volume correction). GMV in the insula and orbitofrontal cortex was also related to suicide lethality (p<0.05, FWE-corrected). The current findings suggest that morphological changes in the FLN could be a signature of previous etiopathogenic processes affecting regions related to suicidality and its severity in BD-I patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  17. Disrupted Gamma Synchrony after Mild Traumatic Brain Injury and Its Correlation with White Matter Abnormality

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    Chao Wang

    2017-10-01

    Full Text Available Mild traumatic brain injury (mTBI has been firmly associated with disrupted white matter integrity due to induced white matter damage and degeneration. However, comparatively less is known about the changes of the intrinsic functional connectivity mediated via neural synchronization in the brain after mTBI. Moreover, despite the presumed link between structural and functional connectivity, no existing studies in mTBI have demonstrated clear association between the structural abnormality of white matter axons and the disruption of neural synchronization. To investigate these questions, we recorded resting state EEG and diffusion tensor imaging (DTI from a cohort of military service members. A newly developed synchronization measure, the weighted phase lag index was applied on the EEG data for estimating neural synchronization. Fractional anisotropy was computed from the DTI data for estimating white matter integrity. Fifteen service members with a history of mTBI within the past 3 years were compared to 22 demographically similar controls who reported no history of head injury. We observed that synchronization at low-gamma frequency band (25–40 Hz across scalp regions was significantly decreased in mTBI cases compared with controls. The synchronization in theta (4–7 Hz, alpha (8–13 Hz, and beta (15–23 Hz frequency bands were not significantly different between the two groups. In addition, we found that across mTBI cases, the disrupted synchronization at low-gamma frequency was significantly correlated with the white matter integrity of the inferior cerebellar peduncle, which was also significantly reduced in the mTBI group. These findings demonstrate an initial correlation between the impairment of white matter integrity and alterations in EEG synchronization in the brain after mTBI. The results also suggest that disruption of intrinsic neural synchronization at low-gamma frequency may be a characteristic functional pathology

  18. Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder

    NARCIS (Netherlands)

    Noordermeer, S.D.; Luman, M.; Greven, C.U.; Veroude, K.; Faraone, S.V.; Hartman, C.A.; Hoekstra, P.J.; Franke, B.; Buitelaar, J.K.; Heslenfeld, D.J.; Oosterlaan, J.

    2017-01-01

    BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with structural abnormalities in total gray matter, basal ganglia, and cerebellum. Findings of structural abnormalities in frontal and temporal lobes, amygdala, and insula are less consistent. Remarkably, the impact of

  19. Structural brain abnormalities in adolescents with autism spectrum disorder and patients with attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Brieber, Sarah; Neufang, Susanne; Bruning, Nicole; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Fink, Gereon R; Konrad, Kerstin

    2007-12-01

    Although autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are two distinct neurodevelopmental diseases, they share behavioural, neuropsychological and neurobiological characteristics. For the identification of endophenotypes across diagnostic categories, further investigations of phenotypic overlap between ADHD and autism at the behavioural, neurocognitive, and brain levels are needed. We examined regional grey matter differences and similarities in children and adolescents with ASD and ADHD in comparison to healthy controls using structural magnetic resonance imaging (MRI) and voxel-based morphometry. With regard to clinical criteria, the clinical groups did not differ with respect to ADHD symptoms; however, only patients with ASD showed deficits in social communication and interaction, according to parental rating. Structural abnormalities across both clinical groups compared to controls became evident as grey matter reductions in the left medial temporal lobe and as higher grey matter volumes in the left inferior parietal cortex. In addition, autism-specific brain abnormalities were found as increased grey matter volume in the right supramarginal gyrus. While the shared structural deviations in the medial temporal lobe might be attributed to an unspecific delay in brain development and might be associated with memory deficits, the structural abnormalities in the inferior parietal lobe may correspond to attentional deficits observed in both ASD and ADHD. By contrast, the autism-specific grey matter abnormalities near the right temporo-parietal junction may be associated with impaired 'theory of mind' abilities. These findings shed some light on both similarities and differences in the neurocognitive profiles of ADHD and ASD patients.

  20. Perinatal factors and regional brain volume abnormalities at term in a cohort of extremely low birth weight infants.

    Directory of Open Access Journals (Sweden)

    Nehal A Parikh

    Full Text Available Our objective was to investigate diverse clinical antecedents of total and regional brain volume abnormalities and white matter hyperintensity volume on term MRI in extremely low birth weight (birth weight ≤1000 g survivors. A consecutive cohort of extremely low birth weight infants who survived to 38 weeks postmenstrual age (n = 122 and a control group of 16 healthy term newborns underwent brain MRI at term-equivalent age. Brain volumes were measured using semi-automated and manual segmentation methods. Using multivariable linear regression, clinical antecedents were correlated with volumes of total brain tissue, white matter hyperintensities, and regional tissues/structures, adjusted for age at MRI, total cranial volume, and total tissue volume. Regional brain volumes were markedly reduced in extremely low birth weight infants as compared to term newborns (relative difference range: -11.0%, -35.9%. Significant adverse clinical associations for total brain tissue volume included: small for gestational age, seizures, caffeine therapy/apnea of prematurity, duration of parenteral nutrition, pulmonary hemorrhage, and white matter injury (p<0.01 for each; relative difference range: -1.4% to -15.0%. Surgery for retinopathy of prematurity and surgery for necrotizing enterocolitis or spontaneous intestinal perforation were significantly associated with increasing volume of white matter hyperintensities. Regional brain volumes are sensitive to multiple perinatal factors and neonatal morbidities or interventions. Brain growth measurements in extremely low birth weight infants can advance our understanding of perinatal brain injury and development.

  1. Curcumin regulates insulin pathways and glucose metabolism in the brains of APPswe/PS1dE9 mice.

    Science.gov (United States)

    Wang, Pengwen; Su, Caixin; Feng, Huili; Chen, Xiaopei; Dong, Yunfang; Rao, Yingxue; Ren, Ying; Yang, Jinduo; Shi, Jing; Tian, Jinzhou; Jiang, Shucui

    2017-03-01

    Recent studies have shown the therapeutic potential of curcumin in Alzheimer's disease (AD). In 2014, our lab found that curcumin reduced Aβ40, Aβ42 and Aβ-derived diffusible ligands in the mouse hippocampus, and improved learning and memory. However, the mechanisms underlying this biological effect are only partially known. There is considerable evidence in brain metabolism studies indicating that AD might be a brain-specific type of diabetes with progressive impairment of glucose utilisation and insulin signalling. We hypothesised that curcumin might target both the glucose metabolism and insulin signalling pathways. In this study, we monitored brain glucose metabolism in living APPswe/PS1dE9 double transgenic mice using a micro-positron emission tomography (PET) technique. The study showed an improvement in cerebral glucose uptake in AD mice. For a more in-depth study, we used immunohistochemical (IHC) staining and western blot techniques to examine key factors in both glucose metabolism and brain insulin signalling pathways. The results showed that curcumin ameliorated the defective insulin signalling pathway by upregulating insulin-like growth factor (IGF)-1R, IRS-2, PI3K, p-PI3K, Akt and p-Akt protein expression while downregulating IR and IRS-1. Our study found that curcumin improved spatial learning and memory, at least in part, by increasing glucose metabolism and ameliorating the impaired insulin signalling pathways in the brain.

  2. Prevalence of undiagnosed abnormal glucose tolerance in adult patients cared for by general practitioners in Hungary. Results of a risk-stratified screening based on FINDRISC questionnaire

    Science.gov (United States)

    Winkler, Gábor; Hidvégi, Tibor; Vándorfi, Győző; Balogh, Sándor; Jermendy, György

    2013-01-01

    Background The prevalence of type 2 diabetes mellitus is rapidly increasing, worldwide and also in Hungary. Timely diagnosis and early treatment could be aided by targeted screening. Recognizing this, the Hungarian Diabetes Association initiated a risk-stratified screening with the involvement of primary care physicians. Material/Methods In the first phase of screening, the FINDRISC questionnaire was completed, followed by an oral glucose tolerance test (OGTT) for those with a score of ≥12. Between September 1, 2010 and March 31, 2011, 70,432 non-diabetic adults, who visited their general practitioners for any reason, were involved in the screening. Of these, 68,476 questionnaires proved to be suitable for processing. Results From the questionnaires, 28,077 (41.0%) had a score of ≥12. A valid OGTT was performed in 22,846 cases; of this group 3,217 subjects (14.1%) had elevated fasting glucose levels, 5,663 (24.8%) had impaired glucose tolerance, and 1,750 (7.6%) had manifest, previously undiagnosed, diabetes mellitus. Overall, from the valid OGTT group, 46.5% subjects had some degree of glucose intolerance. Conclusions Based on the FINDRISC questionnaire, the risk-stratified screening for diabetes mellitus proved to be simple and cost-effective method for the early detection of carbohydrate metabolism disorders. Using this method, the prevalence rate of previously undiagnosed abnormal glucose tolerance was high in adult patients cared for by general practitioners in Hungary. PMID:23344680

  3. Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure?

    Science.gov (United States)

    Morea, Veronica; Bidollari, Eris; Colotti, Gianni; Fiorillo, Annarita; Rosati, Jessica; De Filippis, Lidia; Squitieri, Ferdinando; Ilari, Andrea

    2017-07-01

    Huntington's disease (HD) or Huntington's chorea is the most common inherited, dominantly transmitted, neurodegenerative disorder. It is caused by increased CAG repeats number in the gene coding for huntingtin (Htt) and characterized by motor, behaviour and psychiatric symptoms, ultimately leading to death. HD patients also exhibit alterations in glucose and energetic metabolism, which result in pronounced weight loss despite sustained calorie intake. Glucose metabolism decreases in the striatum of all the subjects with mutated Htt, but affects symptom presentation only when it drops below a specific threshold. Recent evidence points at defects in glucose uptake by the brain, and especially by neurons, as a relevant component of central glucose hypometabolism in HD patients. Here we review the main features of glucose metabolism and transport in the brain in physiological conditions and how these processes are impaired in HD, and discuss the potential ability of strategies aimed at increasing intracellular energy levels to counteract neurological and motor degeneration in HD patients.

  4. Effects of glucose, insulin, and supernatant from pancreatic beta-cells on brain-pancreas relative protein in rat hippocampus

    NARCIS (Netherlands)

    Lin, Yan-Hua; Westenbroek, Christel; Tie, Lu; Liu, Ai-Hua; Yu, He-Ming; Ter Horst, Gert J.; Li, Xue-Jun

    2006-01-01

    Brain-pancreas relative protein (BPRP) is a novel protein that mainly expresses in brain and pancreas. In our previous study, we found that various stressors significantly decreased the expression of BPRP in pancreas in vivo, accompanied by changes in insulin and glucose levels, and that expression

  5. [Changes of glucose in the brains of monkeys with MPTP induced Parkinson's disease].

    Science.gov (United States)

    Li, Peng; Zhang, Zhu-Jun; Li, Yang; Ren, Hai-Bo; Zhang, Shi-Zhen; Wang, Wei

    2013-05-01

    To examine the metabolic and behavioral changes of monkeys with MPTP induced Parkinson's disease. Four healthy monkeys were injected with diluted MPTP solution continuously through peripheral veins. The behavioral changes of the monkeys were monitored with the Parkinson disease scale for monkeys. 18FDG-PET-CT scans for the whole brain were obtained before and 3 months after the injection of MPTP. The pathological and glucose metabolic changes of the brains were examined. The animal model of Parkinson's disease was successfully established in all 4 monkeys, showing typical parkinsonian syndromes of bradykinesia, rigidity and hypokinesia. Changes in high nervous activities such as apathetic and less aggressive behaviors were also observed. Their scores of Parkinson disease scale exceeded 20. The parkinsonian syndromes were relieved after the administration of sinemet. The 18FDG-PET-CT scans showed significant glucose reduction after the MPTP injection within and outside of the basal ganglion area. The metabolic changes of brains in the monkeys with Parkinson's disease are not limited to the basal ganglion area, which may be an important mechanism for the non-motor symptoms.

  6. Abnormal neural connectivity in schizophrenia and fMRI-brain computer interface as a potential therapeutic approach

    Directory of Open Access Journals (Sweden)

    Sergio eRuiz

    2013-03-01

    Full Text Available Considering that single locations of structural and functional abnormalities are insufficient to explain the diverse psychopathology of schizophrenia, new models have postulated that the impairments associated with the disease arise from a failure to integrate the activity of local and distributed neural circuits: the abnormal neural connectivity hypothesis. In the last years, new evidence coming from neuroimaging have supported and expanded this theory. However, despite the increasing evidence that schizophrenia is a disorder of neural connectivity, so far there are no treatments that have shown to produce a significant change in brain connectivity, or that have been specifically designed to alleviate this problem. Brain-Computer Interfaces based on real-time functional Magnetic Resonance Imaging (fMRI-BCI are novel techniques that have allowed subjects to achieve self-regulation of circumscribed brain regions. In recent studies, experiments with this technology have resulted in new findings suggesting that this methodology could be used to train subjects to enhance brain connectivity, and therefore could potentially be used as a therapeutic tool in mental disorders including schizophrenia.The present article summarizes the findings coming from hemodynamics-based neuroimaging that support the abnormal connectivity hypothesis in schizophrenia, and discusses a new approach that could address this problem.

  7. Brain tissue- and region-specific abnormalities on volumetric MRI scans in 21 patients with Bardet-Biedl syndrome (BBS

    Directory of Open Access Journals (Sweden)

    Johnston Jennifer

    2011-07-01

    Full Text Available Abstract Background Bardet-Biedl syndrome (BBS is a heterogeneous human disorder inherited in an autosomal recessive pattern, and characterized by the primary findings of obesity, polydactyly, hypogonadism, and learning and behavioural problems. BBS mouse models have a neuroanatomical phenotype consisting of third and lateral ventriculomegaly, thinning of the cerebral cortex, and reduction in the size of the corpus striatum and hippocampus. These abnormalities raise the question of whether humans with BBS have a characteristic morphologic brain phenotype. Further, although behavioral, developmental, neurological and motor defects have been noted in patients with BBS, to date, there are limited reports of brain findings in BBS. The present study represents the largest systematic evaluation for the presence of structural brain malformations and/or progressive changes, which may contribute to these functional problems. Methods A case-control study of 21 patients, most aged 13-35 years, except for 2 patients aged 4 and 8 years, who were diagnosed with BBS by clinical criteria and genetic analysis of known BBS genes, and were evaluated by qualitative and volumetric brain MRI scans. Healthy controls were matched 3:1 by age, sex and race. Statistical analysis was performed using SAS language with SAS STAT procedures. Results All 21 patients with BBS were found to have statistically significant region- and tissue-specific patterns of brain abnormalities. There was 1 normal intracranial volume; 2 reduced white matter in all regions of the brain, but most in the occipital region; 3 preserved gray matter volume, with increased cerebral cortex volume in only the occipital lobe; 4 reduced gray matter in the subcortical regions of the brain, including the caudate, putamen and thalamus, but not in the cerebellum; and 5 increased cerebrospinal fluid volume. Conclusions There are distinct and characteristic abnormalities in tissue- and region- specific volumes

  8. Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course

    DEFF Research Database (Denmark)

    Mansur, Rodrigo B; Santos, Camila M; Rizzo, Lucas B

    2016-01-01

    OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism...... mellitus. Information related to current and past psychiatric/medical history, as well as prescription of pharmacological treatments was also captured. RESULTS: Individuals with BD had lower levels of BDNF, relative to healthy controls, after adjustment for age, gender, current medications, smoking...

  9. Acute Fornix Deep Brain Stimulation Improves Hippocampal Glucose Metabolism in Aged Mice.

    Science.gov (United States)

    Wang, Xiu; Hu, Wen-Han; Zhang, Kai; Zhou, Jun-Jian; Liu, De-Feng; Zhang, Mei-Yu; Zhang, Jian-Guo

    2018-03-05

    A beneficial memory effect of acute fornix deep brain stimulation (DBS) has been reported in clinical studies. The aim of this study was to investigate the acute changes in glucose metabolism induced by fornix DBS. First, the Morris water maze test and novel object recognition memory test were used to confirm declined memory in aged mice (C57BL/6, 20-22 months old). Then, four groups of mice were used as follows: aged mice with stimulation (n = 12), aged mice with sham-stimulation (n = 8), adult mice (3-4 months old) with stimulation (n = 12), and adult mice with sham-stimulation (n = 8). Ipsilateral hippocampal glucose metabolism and glutamate levels were measured in vivo by microdialysis before, during, and after fornix DBS treatment. Histological staining was used to verify the localization of electrodes and mice with inaccurate placement were excluded from subsequent analyses. The effects of fornix DBS on extracellular glucose, lactate, pyruvate, and glutamate levels over time were analyzed by repeated-measures analysis of variance followed by Fisher's least significant difference post hoc test. The aged mice had a higher basal lactate/pyruvate ratio (LPR) and lactate/glucose ratio (LGR) than the adult mice (LPR: 0.34 ± 0.04 vs. 0.13 ± 0.02, t = 4.626, P Fornix DBS decreased the ipsilateral hippocampal pyruvate and lactate levels (P fornix DBS treatment (P fornix DBS. In addition, fornix DBS significantly decreased the ipsilateral hippocampal extracellular levels of glutamate in aged mice (P fornix DBS could significantly improve hippocampal glucose metabolism in aged mice by promoting cellular aerobic respiration activity.

  10. The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study.

    Science.gov (United States)

    Samaras, Katherine; Lutgers, Helen L; Kochan, Nicole A; Crawford, John D; Campbell, Lesley V; Wen, Wei; Slavin, Melissa J; Baune, Bernard T; Lipnicki, Darren M; Brodaty, Henry; Trollor, Julian N; Sachdev, Perminder S

    2014-04-01

    Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n = 880) and brain volumes by magnetic resonance imaging (n = 312) measured at baseline and 2 years. Primary outcomes were global cognition and total brain volume. Secondary outcomes were cognitive domains (processing speed, memory, language, visuospatial and executive function) and brain volumes (hippocampal, parahippocampal, precuneus and frontal lobe). Participants were categorised as normal, impaired fasting glucose at both assessments (stable IFG), baseline diabetes or incident glucose disorders (incident diabetes or IFG at 2 years). Measures included inflammatory cytokines and oxidative metabolites. Covariates were age, sex, education, non-English speaking background, smoking, blood pressure, lipid-lowering or antihypertensive medications, mood score, apolipoprotein E genotype and baseline cognition or brain volume. Participants with incident glucose disorders had greater decline in global cognition and visuospatial function compared to normal, similar to that observed in baseline diabetes. Homocysteine was independently associated with the observed effect of diabetes on executive function. Apolipoprotein E genotype did not influence the observed effects of diabetes on cognition. Incident glucose disorders and diabetes were also associated with greater 2-year decline in total brain volume, compared to normal (40.0 ± 4.2 vs. 46.7 ± 5.7 mm(3) vs. 18.1 ± 6.2, respectively, p cognition or brain volumes compared to normal. Incident glucose disorders, like diabetes, are

  11. JC virus T-antigen regulates glucose metabolic pathways in brain tumor cells.

    Science.gov (United States)

    Noch, Evan; Sariyer, Ilker Kudret; Gordon, Jennifer; Khalili, Kamel

    2012-01-01

    Recent studies have reported the detection of the human neurotropic virus, JCV, in a significant population of brain tumors, including medulloblastomas. Accordingly, expression of the JCV early protein, T-antigen, which has transforming activity in cell culture and in transgenic mice, results in the development of a broad range of tumors of neural crest and glial origin. Evidently, the association of T-antigen with a range of tumor-suppressor proteins, including p53 and pRb, and signaling molecules, such as β-catenin and IRS-1, plays a role in the oncogenic function of JCV T-antigen. We demonstrate that T-antigen expression is suppressed by glucose deprivation in medulloblastoma cells and in glioblastoma xenografts that both endogenously express T-antigen. Mechanistic studies indicate that glucose deprivation-mediated suppression of T-antigen is partly influenced by 5'-activated AMP kinase (AMPK), an important sensor of the AMP/ATP ratio in cells. In addition, glucose deprivation-induced cell cycle arrest in the G1 phase is blocked with AMPK inhibition, which also prevents T-antigen downregulation. Furthermore, T-antigen prevents G1 arrest and sustains cells in the G2 phase during glucose deprivation. On a functional level, T-antigen downregulation is partially dependent on reactive oxygen species (ROS) production during glucose deprivation, and T-antigen prevents ROS induction, loss of ATP production, and cytotoxicity induced by glucose deprivation. Additionally, we have found that T-antigen is downregulated by the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), and the pentose phosphate inhibitors, 6-aminonicotinamide and oxythiamine, and that T-antigen modulates expression of the glycolytic enzyme, hexokinase 2 (HK2), and the pentose phosphate enzyme, transaldolase-1 (TALDO1), indicating a potential link between T-antigen and metabolic regulation. These studies point to the possible involvement of JCV T-antigen in medulloblastoma proliferation and the metabolic

  12. Abnormalities on magnetic resonance imaging seen acutely following mild traumatic brain injury: correlation with neuropsychological tests and delayed recovery

    International Nuclear Information System (INIS)

    Hughes, David G.; Jackson, Alan; Mason, Damon L.; Berry, Elizabeth; Hollis, Sally; Yates, David W.

    2004-01-01

    Mild traumatic brain injury (MTBI) is a common reason for hospital attendance and is associated with significant delayed morbidity. We studied a series of 80 persons with MTBI. Magnetic resonance imaging (MRI) and neuropsychological testing were used in the acute phase and a questionnaire for post-concussion syndrome (PCS) and return to work status at 6 months. In 26 subjects abnormalities were seen on MRI, of which 5 were definitely traumatic. There was weak correlation with abnormal neuropsychological tests for attention in the acute period. There was no significant correlation with a questionnaire for PCS and return to work status. Although non-specific abnormalities are frequently seen, standard MRI techniques are not helpful in identifying patients with MTBI who are likely to have delayed recovery. (orig.)

  13. Brain White Matter Abnormalities in Female Interstitial Cystitis/Bladder Pain Syndrome: A MAPP Network Neuroimaging Study.

    Science.gov (United States)

    Farmer, Melissa A; Huang, Lejian; Martucci, Katherine; Yang, Claire C; Maravilla, Kenneth R; Harris, Richard E; Clauw, Daniel J; Mackey, Sean; Ellingson, Benjamin M; Mayer, Emeran A; Schaeffer, Anthony J; Apkarian, A Vania

    2015-07-01

    Several chronic pain conditions may be distinguished by condition specific brain anatomical and functional abnormalities on imaging, which are suggestive of underlying disease processes. We present what is to our knowledge the first characterization of interstitial cystitis/bladder pain syndrome associated white matter (axonal) abnormalities based on multicenter neuroimaging from the MAPP Research Network. We assessed 34 women with interstitial cystitis/bladder pain syndrome and 32 healthy controls using questionnaires on pain, mood and daily function. White matter microstructure was evaluated by diffusion tensor imaging to model directional water flow along axons or fractional anisotropy. Regions correlating with clinical parameters were further examined for gender and syndrome dependence. Women with interstitial cystitis/bladder pain syndrome showed numerous white matter abnormalities that correlated with pain severity, urinary symptoms and impaired quality of life. Interstitial cystitis/bladder pain syndrome was characterized by decreased fractional anisotropy in aspects of the right anterior thalamic radiation, the left forceps major and the right longitudinal fasciculus. Increased fractional anisotropy was detected in the right superior and bilateral inferior longitudinal fasciculi. To our knowledge we report the first characterization of brain white matter abnormalities in women with interstitial cystitis/bladder pain syndrome. Regional decreases and increases in white matter integrity across multiple axonal tracts were associated with symptom severity. Given that white matter abnormalities closely correlated with hallmark symptoms of interstitial cystitis/bladder pain syndrome, including bladder pain and urinary symptoms, brain anatomical alterations suggest that there are neuropathological contributions to chronic urological pelvic pain. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

  14. Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer.

    Science.gov (United States)

    Kiebish, Michael A; Han, Xianlin; Cheng, Hua; Chuang, Jeffrey H; Seyfried, Thomas N

    2008-12-01

    Otto Warburg first proposed that cancer originated from irreversible injury to mitochondrial respiration, but the structural basis for this injury has remained elusive. Cardiolipin (CL) is a complex phospholipid found almost exclusively in the inner mitochondrial membrane and is intimately involved in maintaining mitochondrial functionality and membrane integrity. Abnormalities in CL can impair mitochondrial function and bioenergetics. We used shotgun lipidomics to analyze CL content and composition in highly purified brain mitochondria from the C57BL/6J (B6) and VM/Dk (VM) inbred strains and from subcutaneously grown brain tumors derived from these strains to include an astrocytoma and ependymoblastoma (B6 tumors), a stem cell tumor, and two microgliomas (VM tumors). Major abnormalities in CL content or composition were found in all tumors. The compositional abnormalities involved an abundance of immature molecular species and deficiencies of mature molecular species, suggesting major defects in CL synthesis and remodeling. The tumor CL abnormalities were also associated with significant reductions in both individual and linked electron transport chain activities. A mathematical model was developed to facilitate data interpretation. The implications of our findings to the Warburg cancer theory are discussed.

  15. Abnormal temporal lobe response in Alzheimer's disease during cognitive processing as measured by 11C-2-deoxy-D-glucose and PET

    International Nuclear Information System (INIS)

    Miller, J.D.; de Leon, M.J.; Ferris, S.H.; Kluger, A.; George, A.E.; Reisberg, B.; Sachs, H.J.; Wolf, A.P.

    1987-01-01

    Elderly controls and probable Alzheimer's disease patients underwent serial positron emission tomography (PET) studies during a baseline condition and while performing a verbal memory task. For the temporal lobes, all 7 Alzheimer patients demonstrated a relative shift in glucose metabolic rates to the right hemisphere during the memory condition relative to baseline, and 5 of 7 controls showed a shift to the left hemisphere. Baseline absolute regional metabolic rates replicate previous findings and were somewhat less useful than the memory challenge in differentiating patients from controls. These results indicate that a temporal lobe abnormality in Alzheimer's disease is related to memory performance

  16. Increased Brain Glucose Uptake After 12 Weeks of Aerobic High-Intensity Interval Training in Young and Older Adults.

    Science.gov (United States)

    Robinson, Matthew M; Lowe, Val J; Nair, K Sreekumaran

    2018-01-01

    Aerobic exercise training can increase brain volume and blood flow, but the impact on brain metabolism is less known. We determined whether high-intensity interval training (HIIT) increases brain metabolism by measuring brain glucose uptake in younger and older adults. Brain glucose uptake was measured before and after HIIT or a sedentary (SED) control period within a larger exercise study. Study procedures were performed at the Mayo Clinic in Rochester, MN. Participants were younger (18 to 30 years) or older (65 to 80 years) SED adults who were free of major medical conditions. Group sizes were 15 for HIIT (nine younger and six older) and 12 for SED (six younger and six older). Participants completed 12 weeks of HIIT or SED. HIIT was 3 days per week of 4 × 4 minute intervals at over 90% of peak aerobic capacity (VO2peak) with 2 days per week of treadmill walking at 70% VO2peak. Resting brain glucose uptake was measured using 18F-fluorodeoxyglucose positron emission tomography scans at baseline and at week 12. Scans were performed at 96 hours after exercise. VO2peak was measured by indirect calorimetry. Glucose uptake increased significantly in the parietal-temporal and caudate regions after HIIT compared with SED. The gains with HIIT were not observed in all brain regions. VO2peak was increased for all participants after HIIT and did not change with SED. We demonstrate that brain glucose metabolism increased after 12 weeks of HIIT in adults in regions where it is reduced in Alzheimer's disease.

  17. Abnormal release of incretins and cortisol after oral glucose in subjects with insulin-resistant myotonic dystrophy

    DEFF Research Database (Denmark)

    Johansson, Asa; Olsson, Tommy; Cederquist, Kristina

    2002-01-01

    . An interesting model for the study of hormonal perturbations accompanying marked insulin resistance without concomitant diabetes is myotonic dystrophy (DM1). DESIGN: The work was carried out in an out-patient setting. METHODS: An oral glucose tolerance test was performed in 18 males with DM1 and 18 controls...... to examine the release of incretins and counter-regulatory hormones. Genetic analyses were also performed in patients. RESULTS: We found that the increment in GLP-1 after oral glucose was significantly greater in patients, while there was no significant difference in GIP or glucagon responses between...... patients and controls, although long CTG repeat expansions were associated with a more pronounced GIP response. Interestingly, the GLP-1 response to oral glucose correlated with the insulin response in patients but not in controls whereas, in controls, the insulin response closely correlated with the GIP...

  18. The genetic and environmental determinants of the association between brain abnormalities and schizophrenia: the schizophrenia twins and relatives consortium.

    Science.gov (United States)

    van Haren, Neeltje E M; Rijsdijk, Fruhling; Schnack, Hugo G; Picchioni, Marco M; Toulopoulou, Timothea; Weisbrod, Matthias; Sauer, Heinrich; van Erp, Theo G; Cannon, Tyrone D; Huttunen, Matti O; Boomsma, Dorret I; Hulshoff Pol, Hilleke E; Murray, Robin M; Kahn, Rene S

    2012-05-15

    Structural brain abnormalities are consistently found in schizophrenia (Sz) and have been associated with the familial risk for the disorder. We aim to define the relative contributions of genetic and nongenetic factors to the association between structural brain abnormalities and Sz in a uniquely powered cohort (Schizophrenia Twins and Relatives consortium). An international multicenter magnetic resonance imaging collaboration was set up to pool magnetic resonance imaging scans from twin pairs in Utrecht (The Netherlands), Helsinki (Finland), London (United Kingdom), and Jena (Germany). A sample of 684 subjects took part, consisting of monozygotic twins (n = 410, with 51 patients from concordant and 52 from discordant pairs) and dizygotic twins (n = 274, with 39 patients from discordant pairs). The additive genetic, common, and unique environmental contributions to the association between brain volumes and risk for Sz were estimated by structural equation modeling. The heritabilities of most brain volumes were significant and ranged between 52% (temporal cortical gray matter) and 76% (cerebrum). Heritability of cerebral gray matter did not reach significance (34%). Significant phenotypic correlations were found between Sz and reduced volumes of the cerebrum (-.22 [-.30/-.14]) and white matter (-.17 [-.25/-.09]) and increased volume of the third ventricle (.18 [.08/.28]). These were predominantly due to overlapping genetic effects (77%, 94%, and 83%, respectively). Some of the genes that transmit the risk for Sz also influence cerebral (white matter) volume. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. The effect of inhibition of hexose-monophosphate shunt on the metabolism of glucose and function in rat brain in vivo

    International Nuclear Information System (INIS)

    Gaitonde, M.K.; Evans, G.M.

    1982-01-01

    Rats treated 4 hr previously with 6-aminonicotinamide showed a twenty-four fold increase of [ 14 C]phosphogluconate in the adult brain at 30 min after intection of [U- 14 C]glucose indicating a blockade of the hexosemmonophosphate shunt. There was a significant increase in the 14 C-content of glucose and glucose-6-phosphate, and a decrease in that of amino acids. [ 14 C]Phosphoglycerate content showed no consistent change after 6-aminonicotinamide treatment. The concentration of glucose and glucose 6-phosphate increased significantly without a significant change in the lactate pool in the brain of 6-aminonicotinamide treated rats. The rate of utilization of glucose in the brain of control rats was 0.73 mumol/min per g of brain. It decreased by 16% in rats treated with 6-aminonicotinamide; the results suggested that both glycolysis and pyruvate oxidation were affected. The amount of glucose utilized in the brain by the hexosemonophosphate shunt was approximately 0.0093 mumol/min per g of brain, i.e. 1.3% of the total rate of utilization of glucose. The observed changes were not due to hypothermia. The rate of glucose utilization was higher in animals exposed to higher ambient temperature and to stress caused by handling. The results were explained by postulating a role for the hexosemonophosphate shunt in providing neurotransmitter amino acids glutamate and gamma-aminobutyrate, and interdependence of brain function and glucose utilization

  20. Valine pyrrolidide preserves intact glucose-dependent insulinotropic peptide and improves abnormal glucose tolerance in minipigs with reduced beta-cell mass

    DEFF Research Database (Denmark)

    Larsen, Marianne Olholm; Rolin, Bidda; Ribel, Ulla

    2003-01-01

    for type 2 diabetes was evaluated in a new large animal model of insulin-deficient diabetes and reduced beta-cell mass, the nicotinamide (NIA) (67 mg/kg) and streptozotocin (STZ) (125 mg/kg)-treated minipig, using the DPPIV inhibitor, valine pyrrolidide (VP) (50 mg/kg). VP did not significantly affect...... glucose tolerance test (OGTT) but increased the insulinogenic index in normal animals (from 83 +/- 42 to 192 +/- 108; P animals. GIP seems to contribute to the antihyperglycemic effect of VP in this model...

  1. Annual research review: Growth connectomics--the organization and reorganization of brain networks during normal and abnormal development.

    Science.gov (United States)

    Vértes, Petra E; Bullmore, Edward T

    2015-03-01

    We first give a brief introduction to graph theoretical analysis and its application to the study of brain network topology or connectomics. Within this framework, we review the existing empirical data on developmental changes in brain network organization across a range of experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans). We discuss preliminary evidence and current hypotheses for how the emergence of network properties correlates with concomitant cognitive and behavioural changes associated with development. We highlight some of the technical and conceptual challenges to be addressed by future developments in this rapidly moving field. Given the parallels previously discovered between neural systems across species and over a range of spatial scales, we also review some recent advances in developmental network studies at the cellular scale. We highlight the opportunities presented by such studies and how they may complement neuroimaging in advancing our understanding of brain development. Finally, we note that many brain and mind disorders are thought to be neurodevelopmental in origin and that charting the trajectory of brain network changes associated with healthy development also sets the stage for understanding abnormal network development. We therefore briefly review the clinical relevance of network metrics as potential diagnostic markers and some recent efforts in computational modelling of brain networks which might contribute to a more mechanistic understanding of neurodevelopmental disorders in future. © 2014 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

  2. Annual Research Review: Growth connectomics – the organization and reorganization of brain networks during normal and abnormal development

    Science.gov (United States)

    Vértes, Petra E; Bullmore, Edward T

    2015-01-01

    Background We first give a brief introduction to graph theoretical analysis and its application to the study of brain network topology or connectomics. Within this framework, we review the existing empirical data on developmental changes in brain network organization across a range of experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans). Synthesis We discuss preliminary evidence and current hypotheses for how the emergence of network properties correlates with concomitant cognitive and behavioural changes associated with development. We highlight some of the technical and conceptual challenges to be addressed by future developments in this rapidly moving field. Given the parallels previously discovered between neural systems across species and over a range of spatial scales, we also review some recent advances in developmental network studies at the cellular scale. We highlight the opportunities presented by such studies and how they may complement neuroimaging in advancing our understanding of brain development. Finally, we note that many brain and mind disorders are thought to be neurodevelopmental in origin and that charting the trajectory of brain network changes associated with healthy development also sets the stage for understanding abnormal network development. Conclusions We therefore briefly review the clinical relevance of network metrics as potential diagnostic markers and some recent efforts in computational modelling of brain networks which might contribute to a more mechanistic understanding of neurodevelopmental disorders in future. PMID:25441756

  3. Over-estimation of glucose-6-phosphatase activity in brain in vivo. Apparent difference in rates of [2-3H]glucose and [U-14C]glucose utilization is due to contamination of precursor pool with 14C-labeled products and incomplete recovery of 14C-labeled metabolites

    International Nuclear Information System (INIS)

    Dienel, G.A.; Nelson, T.; Cruz, N.F.; Jay, T.; Crane, A.M.; Sokoloff, L.

    1988-01-01

    Significant dephosphorylation of glucose 6-phosphate due to glucose-6-phosphatase activity in rat brain in vivo was recently reported. The evidence was an apparent more rapid 3 H than 14 C loss from the glucose pool and faster [2- 3 H]glucose than [U- 14 C]glucose utilization following pulse labeling of the brain with [2- 3 H,U- 14 C]glucose. Radiochemical purity of the glucose and quantitative recovery of the labeled products of glucose metabolism isolated from the brain were obviously essential requirements of their study, but no evidence for purity and recovery was provided. When we repeated these experiments with the described isolation procedures, we replicated the results, but found that: 1) the precursor glucose pool contained detritiated, 14 C-labeled contaminants arising from glucose metabolism, particularly 2-pyrrolidone-5-carboxylic acid derived from [ 14 C]glutamine; 2) [ 14 C]glucose metabolite were not quantitatively recovered; 3) the procedure used to isolate the glucose itself produced detritiated, 14 C-labeled derivatives of [2- 3 H,U-14C]glucose. These deficiencies in the isolation procedures could fully account for the observations that were interpreted as evidence of significant glucose 6-phosphate dephosphorylation by glucose-6-phosphatase activity. When glucose was isolated by more rigorous procedures and its purity verified in the present studies, no evidence for such activity in rat brain was found

  4. Study on the insulin resistance and β-cell function in individuals with normal and those with abnormal glucose metabolism

    International Nuclear Information System (INIS)

    Wei Zikun

    2006-01-01

    Objective: To study the insulin resistance and β-cell function in individuals with normal glucose tolerance (NGT) and those with glucose metabolism dysfunction. Methods: Insulin resistance and β-cell function were studied with oral glucose tolerance test and the following parameters: 2h insulin/2h plasma glucose (2hIns/2hPG), insulin resistance index (IRI), insulin sensitivity index (ISI) and 30 min net increment of insulin/30min net increment of glucose (AI 30 /AG 30 ) were examined in 44 individuals with NGT, 45 subjects with impaired glucose tolerance (IGT), 66 recently diagnosed diabetics and 175 well-established diabetics. Results: The insulin resistance index (IRI) increased progressively from that in NGT individuals to that in recently diabetics (20 ± 1. 5→3.1 ± 1.6→4.1 ± 1.8), while the 2hIns/2hPG, ΔI 30 /ΔG 30 and ISI decreased progressively with significant differences between those in successive groups (P 30 /ΔG 30 and ISI kept decreasing (values in patients with disease history less than 3 yrs vs those in patients with disease over 3yrs: 2.9 ± 3.2 vs 2.4 + 2.3, 30.2 + 1.1 vs 23.4 ± 2.3, P 30 /ΔG 30 were significantly correlated with ISI (F =96.3, 58.4 and 47.5 respectively). For principal component analysis display, the cumulative contribution rate of four parameters (2hIns/2hPG, ISI, ΔI 30 /ΔG 30 and 2h C-peptide) exceeded 85% (86.5%). Conclusion: As the dysfunction of glucose metabolism proceeded from IGT to well established diabetes, the IR increased first with decrease of β-cell secretion followed. The parameters 2hIns/2hPG, ISI, 2h C-peptide ΔI 30 /ΔG 30 were especially useful for the investigation . (authors)

  5. Gestational diabetes is a herald of NIDDM in Navajo women. High rate of abnormal glucose tolerance after GDM.

    Science.gov (United States)

    Steinhart, J R; Sugarman, J R; Connell, F A

    1997-06-01

    To estimate the rate of deterioration of glucose tolerance and evaluate risk factors for development of NIDDM in Navajo women with a history of gestational diabetes mellitus (GDM). A retrospective analysis of 111 GDM deliveries over a 4-year period, 1983-1987, was conducted in 1994 to determine glucose tolerance status. Patients who had not developed NIDDM were recalled for a 2-h glucose tolerance test (GTT). Tested and non-tested patients were compared, as estimate of conversion to NIDDM was calculated, and risk factors for NIDDM were evaluated. A life-table analysis was developed to estimate the probability of NIDDM after GDM. At the time of chart review, 32 patients (29%) had already been diagnosed with NIDDM. Of the patients, 79 were offered GTT testing, and 56 (71%) returned for follow-up; 15 were diagnosed with NIDDM and 17 with impaired glucose tolerance (IGT); 47 (42%) and 64 (58%) patients in the cohort had developed NIDDM or NIDDM/IGT at the conclusion of the study period. Patients who developed NIDDM had greater BMIs, parity, and infant weights. Fasting blood glucose > 5.83 mmol/l, GTT > 41.63 mmol/l, and recurrence of GDM were associated with later NIDDM. A life-table analysis estimated a 53% likelihood of having NIDDM at an 11-year follow-up; a second model, based only on patients with known NIDDM status, predicted a 70% rate of NIDDM at an 11-year follow-up. A high proportion of Navajo women with GDM progressed to NIDDM. Postpartum counseling and periodic GTTs are recommended.

  6. Neuroprotective effects of cactus polysaccharide on oxygen and glucose deprivation induced damage in rat brain slices.

    Science.gov (United States)

    Huang, Xianju; Li, Qin; Zhang, Yingpei; Lü, Qing; Guo, Lianjun; Huang, Lin; He, Zhi

    2008-06-01

    1. The neuroprotective effect of cactus polysaccharide (CP) on oxygen and glucose deprivation (OGD) and reoxygenation (REO)-induced damage in the cortical and hippocampal slices of rat brain was investigated. 2. Cell viability was evaluated by using the 2, 3, 5-triphenyl tetrazolium chloride (TTC) method. The fluorescence of propidium iodide (PI) staining was used for quantification of cellular survival, and lactate dehydrogenase (LDH) activity in incubation medium was assessed by LDH assay to evaluate the degree of injury. 3. The OGD ischemic condition significantly decreased cellular viability and increased LDH release in the incubation medium. CP (0.2 mg/l approximately 2 mg/l) protected brain slices from OGD injury in a dosage dependent manner as demonstrated by increased A 490 value of TTC, decreased PI intensity and LDH release. At the above concentration, CP also prevented the increase of nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity induced by OGD. 4. CP can protect the brain slices (cortical and hippocampus) against injury induced by OGD. Its neuroprotective effect may be partly mediated by the NO/iNOS system induced by OGD insult.

  7. A community-based survey for different abnormal glucose metabolism among pregnant women in a random household study (SAUDI-DM)

    Science.gov (United States)

    Al-Rubeaan, Khalid; Al-Manaa, Hamad A; Khoja, Tawfik A; Youssef, Amira M; Al-Sharqawi, Ahmad H; Siddiqui, Khalid; Ahmad, Najlaa A

    2014-01-01

    Objective To assess the prevalence and risk factors of gestational diabetes mellitus (GDM) in a population known to have a high prevalence of abnormal glucose metabolism. Methods A household random population-based cross-sectional study of 13 627 women in the childbearing age, who were subjected to fasting plasma glucose if they were not known to have been diagnosed before with any type of diabetes. GDM cases were diagnosed using the International Association of Diabetes and Pregnancy Study Group (IAPSG) criteria. Results The overall GDM prevalence was 36.6%, categorised into 32.4% new cases and 4.2% known cases. Another 3.6% had preconception type 1 or 2 diabetes. GDM cases were older and had a significantly higher body mass index, in addition to a higher rate of macrocosmic baby and history of GDM. Monthly income, educational level, living in urban areas and smoking were not found to be significantly different between normal and GDM cases. The most important and significant risk factors for GDM were history of GDM, macrosomic baby, obesity and age >30 years. However, hypertension, low high-density lipoprotein, family history of diabetes and increased triglycerides did not show any significant effect on GDM prevalence in this cohort. Conclusions This society is facing a real burden of abnormal glucose metabolism during pregnancy, where almost half of the pregnant women are subjected to maternal and neonatal complications. Early screening of pregnant women, especially those at a high risk for GDM, is mandatory to identify and manage those cases. PMID:25138813

  8. Acarbose, the α-glucosidase inhibitor, attenuates the blood pressure and splanchnic blood flow responses to meal in elderly patients with postprandial hypotension concomitant with abnormal glucose metabolism.

    Science.gov (United States)

    Qiao, Wei; Li, Jing; Li, Ying; Qian, Duan; Chen, Lei; Wei, Xiansen; Jin, Jiangli; Wang, Yong

    2016-02-01

    Postprandial hypotension (PPH) is a unique clinical phenomenon in the elderly, but its underlying pathogenesis has not been completely elucidated, and drug treatment is still in clinical exploratory stage. The aim of the study was to evaluate the relationship between the fall in postprandial blood pressure and splanchnic blood flow, and to provide a theoretical basis for the treatment of PPH by taking acarbose. The study included 20 elderly inpatients diagnosed with PPH concomitant with abnormal glucose metabolism at stable condition. They were treated with 50 mg acarbose with their meal to observe the changes in blood pressure, heart rate, and blood glucose level, and to monitor the hemodynamics of the superior mesenteric artery (SMA) before and after treatment. Without acarbose treatment, patients after a meal had significantly decreased systolic and diastolic blood pressure, faster postprandial heart rate, higher postprandial glucose level at each period, and increased postprandial SMA blood flow compared with that at fasting state (P<0.05). Acarbose treatment significantly attenuated the decrease of postprandial systolic blood pressures from 35.50±12.66 to 22.25±6.90 mmHg (P=0.000), the increase of heart rate from 9.67±5.94 to 5.33±3.20 beats/min (P=0.016), the increase of postprandial blood glucose from 3.55±1.69 to 2.28±1.61 mmol/l (P=0.000), the increase of postprandial SMA blood flow from 496.80±147.15 to 374.55±97.89 ml/min (P=0.031), and the incidence of PPH, syncope, falls, dizziness, weakness, and angina pectoris (P<0.05). The maximal decrease of postprandial systolic blood pressure was positively associated with the maximal increase in postprandial SMA blood flow (r=0.351, P=0.026). Acarbose treatment showed no significant side effects. The increase in postprandial splanchnic perfusion is one of the reasons for PPH formation. Acarbose may exert its role in PPH treatment by reducing postprandial gastrointestinal blood perfusion. Giving

  9. Brain Microstructural Abnormalities Are Related to Physiological Alterations in End-Stage Renal Disease

    OpenAIRE

    Bai, Zhigang; Ma, Xiaofen; Tian, Junzhang; Dong, Jianwei; He, Jinlong; Zhan, Wenfeng; Xu, Lijuan; Xu, Yikai; Jiang, Guihua

    2016-01-01

    Purpose To study whole-brain microstructural alterations in patients with end-stage renal disease (ESRD) and examine the relationship between brain microstructure and physiological indictors in the disease. Materials and Methods Diffusion tensor imaging data were collected from 35 patients with ESRD (28 men, 18?61 years) and 40 age- and gender-matched healthy controls (HCs, 32 men, 22?58 years). A voxel-wise analysis was then used to identify microstructural alterations over the whole brain i...

  10. Prevalence of endocrine diseases and abnormal glucose tolerance tests in 340 caucasian premenopausal women with hirsutism as the referral diagnosis

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Henriksen, Jan Erik; Andersen, Marianne

    2004-01-01

    OBJECTIVE: To perform an audit on the examination of hirsute patients and to establish a rational routine examination program in an outpatient endocrine clinic. DESIGN: Systematic, retrospective audit. SETTING: Academic tertiary-care medical center. PATIENT(S): Three hundred forty women...... with hirsutism as the referral diagnosis. INTERVENTION(S): Hormone analyses and ACTH tests during cycle days 2-8, 2 hours of oral glucose tolerance test (OGTT), and vaginal ultrasound. MAIN OUTCOME MEASURE(S): End diagnosis, fasting, 30-, 60-, and 120-minute oral glucose-stimulated levels of insulin....... During OGTT, 4.9% (13 of 263) had previously undiagnosed diabetes; no significant difference in diabetes prevalence was found between idiopathic hirsutism and PCOS. For 50.8%, fasting insulin values were in the upper quartile for a reference population. CONCLUSION(S): Initial evaluation of hirsute...

  11. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Ming-Xiong Huang

    2014-01-01

    Full Text Available Traumatic brain injury (TBI is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1–4 Hz that can be measured and localized by resting-state magnetoencephalography (MEG. In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1–4 Hz from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes, our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes, blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI.

  12. Long-term exposure to abnormal glucose levels alters drug metabolism pathways and insulin sensitivity in primary human hepatocytes

    Science.gov (United States)

    Davidson, Matthew D.; Ballinger, Kimberly R.; Khetani, Salman R.

    2016-06-01

    Hyperglycemia in type 2 diabetes mellitus has been linked to non-alcoholic fatty liver disease, which can progress to inflammation, fibrosis/cirrhosis, and hepatocellular carcinoma. Understanding how chronic hyperglycemia affects primary human hepatocytes (PHHs) can facilitate the development of therapeutics for these diseases. Conversely, elucidating the effects of hypoglycemia on PHHs may provide insights into how the liver adapts to fasting, adverse diabetes drug reactions, and cancer. In contrast to declining PHH monocultures, micropatterned co-cultures (MPCCs) of PHHs and 3T3-J2 murine embryonic fibroblasts maintain insulin-sensitive glucose metabolism for several weeks. Here, we exposed MPCCs to hypo-, normo- and hyperglycemic culture media for ~3 weeks. While albumin and urea secretion were not affected by glucose level, hypoglycemic MPCCs upregulated CYP3A4 enzyme activity as compared to other glycemic states. In contrast, hyperglycemic MPCCs displayed significant hepatic lipid accumulation in the presence of insulin, while also showing decreased sensitivity to insulin-mediated inhibition of glucose output relative to a normoglycemic control. In conclusion, we show for the first time that PHHs exposed to hypo- and hyperglycemia can remain highly functional, but display increased CYP3A4 activity and selective insulin resistance, respectively. In the future, MPCCs under glycemic states can aid in novel drug discovery and mechanistic investigations.

  13. Electro-physiological changes in the brain induced by caffeine or glucose nasal spray.

    Science.gov (United States)

    De Pauw, K; Roelands, B; Van Cutsem, J; Marusic, U; Torbeyns, T; Meeusen, R

    2017-01-01

    A direct link between the mouth cavity and the brain for glucose (GLUC) and caffeine (CAF) has been established. The aim of this study is to determine whether a direct link for both substrates also exist between the nasal cavity and the brain. Ten healthy male subjects (age 22 ± 1 years) performed three experimental trials, separated by at least 2 days. Each trial included a 20-s nasal spray (NAS) period in which solutions placebo (PLAC), GLUC, or CAF were provided in a double-blind, randomized order. During each trial, four cognitive Stroop tasks were performed: two familiarization trials and one pre- and one post-NAS trial. Reaction times and accuracy for different stimuli (neutral, NEUTR; congruent, CON; incongruent INCON) were determined. Electroencephalography was continuously measured throughout the trials. During the Stroop tasks pre- and post-NAS, the P300 was assessed and during NAS, source localization was performed using standardized low-resolution brain electromagnetic tomography (sLORETA). NAS activated the anterior cingulate cortex (ACC). CAF-NAS also increased θ and β activity in frontal cortices. Furthermore, GLUC-NAS increased the β activity within the insula. GLUC-NAS also increased the P300 amplitude with INCON (P = 0.046) and reduced P300 amplitude at F3-F4 and P300 latency at CP1-CP2-Cz with NEUTR (P = 0.001 and P = 0.016, respectively). The existence of nasal bitter and sweet taste receptors possibly induce these brain responses. Greater cognitive efficiency was observed with GLUC-NAS. CAF-NAS activated cingulate, insular, and sensorymotor cortices, whereas GLUC-NAS activated sensory, cingulate, and insular cortices. However, no effect on the Stroop task was found.

  14. Characterization of subtle brain abnormalities in a mouse model of Hedgehog pathway antagonist-induced cleft lip and palate.

    Science.gov (United States)

    Lipinski, Robert J; Holloway, Hunter T; O'Leary-Moore, Shonagh K; Ament, Jacob J; Pecevich, Stephen J; Cofer, Gary P; Budin, Francois; Everson, Joshua L; Johnson, G Allan; Sulik, Kathleen K

    2014-01-01

    Subtle behavioral and cognitive deficits have been documented in patient cohorts with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits are associated with structural brain abnormalities but have been limited to adolescent and adult populations where brain plasticity during infancy and childhood may be a confounding factor. Here, we employed high resolution magnetic resonance microscopy to examine primary brain morphology in a mouse model of OFCs. Transient in utero exposure to the Hedgehog (Hh) signaling pathway antagonist cyclopamine resulted in a spectrum of facial dysmorphology, including unilateral and bilateral cleft lip and palate, cleft of the secondary palate only, and a non-cleft phenotype marked by midfacial hypoplasia. Relative to controls, cyclopamine-exposed fetuses exhibited volumetric differences in several brain regions, including hypoplasia of the pituitary gland and olfactory bulbs, hyperplasia of the forebrain septal region, and expansion of the third ventricle. However, in affected fetuses the corpus callosum was intact and normal division of the forebrain was observed. This argues that temporally-specific Hh signaling perturbation can result in typical appearing OFCs in the absence of holoprosencephaly--a condition classically associated with Hh pathway inhibition and frequently co-occurring with OFCs. Supporting the premise that some forms of OFCs co-occur with subtle brain malformations, these results provide a possible ontological basis for traits identified in clinical populations. They also argue in favor of future investigations into genetic and/or environmental modulation of the Hh pathway in the etiopathogenesis of orofacial clefting.

  15. Effect of gamma-hydroxybutyrate on local and global glucose metabolism in the anesthetized cat brain.

    Science.gov (United States)

    Haller, C; Mende, M; Schuier, F; Schuh, R; Schröck, H; Kuschinsky, W

    1990-07-01

    This study addresses three topics in the chloralose-anesthetized cat: (a) distribution of local CMRglc: values ranging from 5 to 109 mumols/100 g/min were found in 37 brain structures and the mean CMRglc over all examined structures was 30.6 mumols/100 g/min; (b) effect of gamma-hydroxybutyrate (GHB, 250 mg/kg i.v.) on local CMRglc, which was significantly (p less than 0.05) depressed in 16 of 37 structures, most prominently in the auditory system, and the mean CMRglc over all structures after GHB was 20.4 mumols/100 g/min; and (c) global values of CMRglc, CMRO2, and CBF before and after GHB: in these experiments, a modified Kety-Schmidt technique was employed measuring saturation/desaturation of inhaled H2 and concentrations of glucose and oxygen in aortic and sagittal sinus blood. CBF and CMRO2 were not altered after GHB, whereas CMRglc was significantly decreased from 35.7 to 28.8 mumols/100 g/min. The values of CMRglc obtained with both techniques (autoradiography and the Kety-Schmidt technique) are concordant, especially when considering the different sampling areas of both methods. The main finding of the present study is a reduction in cerebral glucose consumption after GHB, irrespective of the technique of measurement. This reduction occurs at an unchanged CMRO2 and CBF.

  16. Insulin resistance and reduced brain glucose metabolism in the aetiology of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Amy L. Berger

    2016-12-01

    Full Text Available Significant epidemiological and clinical evidence has emerged that suggests Alzheimer’s disease (AD can be added to the list of chronic illnesses that are primarily caused by modern diets and lifestyles at odds with human physiology. High intakes of refined carbohydrates insufficient physical activity, suboptimal sleep quantity and quality, and other factors that may contribute to insulin resistance combine to create a perfect storm of glycation and oxidative stress in the brain. Specific neurons lose the ability to metabolise and harness energy from glucose, ultimately resulting in neuronal degeneration and death. Simultaneously, chronic peripheral hyperinsulinaemia prevents ketogenesis, thus depriving struggling neurons of a highly efficient alternative fuel substrate. The intimate association between type 2 diabetes and AD suggests that they have common underlying causes, namely insulin resistance and perturbed glucose metabolism. Preclinical evidence of AD is detectable decades before over symptoms appear, indicating that AD progresses over time, with observable signs manifesting only after the brain’s compensatory mechanisms have failed and widespread neuronal atrophy begins to interfere with cognition and performance of daily life tasks. That dietary and environmental triggers play pivotal roles in causing AD suggests that nutrition and lifestyle based interventions may hold the key to ameliorating or preventing this debilitating condition for which conventional pharmaceutical treatments are largely ineffective. Results from small scale clinical studies indicate that dietary and lifestyle strategies may be effective for reversing dementia and cognitive impairment. Increased research efforts should be dedicated towards this promising avenue in the future.

  17. Monitoring arterio-venous differences of glucose and lactate in the anesthetized rat with or without brain damage with ultrafiltration and biosensor technology

    NARCIS (Netherlands)

    Leegsma-Vogt, G; Venema, K; Postema, F; Korf, J

    2001-01-01

    Continuous monitoring of arterio-venous glucose and lactate differences may serve as a diagnostic tool to assess normal brain function and brain pathology. We describe a method and some results obtained with arterio-venous measurements of glucose and lactate in the blood of the

  18. Glucose and cardiovascular risk

    NARCIS (Netherlands)

    Fuchs, M.; Hoekstra, J. B. L.; Mudde, A. H.

    2002-01-01

    The American Diabetes Association and the World Health Organisation have recently redefined the spectrum of abnormal glucose tolerance. The criteria for diabetes mellitus were sharpened and impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were classified as intermediate stages

  19. Brain Transport Profiles of Ginsenoside Rb1 by Glucose Transporter 1: In Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Yu-Zhu Wang

    2018-04-01

    Full Text Available Ginsenoside Rb1 (Rb1 has been demonstrated its protection for central nervous system and is apparently highly distributed to the brain. The objective of this study was to characterize Rb1 transport at the blood–brain barrier (BBB using primary cultured rat brain microvascular endothelial cells (rBMEC, an in vitro BBB model. The initial uptake velocity of Rb1 in rBMEC was temperature- and concentration-dependent, and was significantly reduced by phloretin, an inhibitor of GLUT1 transporter, but was independent of metabolic inhibitor. Furthermore, the transport of Rb1 into rBMEC was significantly diminished in the presence of natural substrate α-D-glucose, suggesting a facilitated transport of Rb1 via GLUT1 transporter. The impact of GLUT1 on the distribution of Rb1 between brain and plasma was studied experimentally in rats. Administration of phloretin (5 mg/kg, i.v. to normal rats for consecutive 1 week before Rb1 (10 mg/kg, i.v. at 0.5, 2, and 6 h did not alter Rb1 concentrations in plasma, but resulted in significant decreased brain concentrations of Rb1 compared to in the phloretin-untreated normal rats (489.6 ± 58.3 versus 105.1 ± 15.1 ng/g, 193.8 ± 11.1 versus 84.8 ± 4.1 ng/g, and 114.2 ± 24.0 versus 39.9 ± 4.9 ng/g, respectively. The expression of GLUT1 in the phloretin-treated group by western blotting analysis in vitro and in vivo experiments was significantly decreased, indicating that the decreased transport of Rb1 in brain was well related to the down-regulated function and level of GLUT1. Therefore, our in vitro and in vivo results indicate that the transport of Rb1 at the BBB is at least partly mediated by GLUT1 transporter.

  20. CSF glucose test

    Science.gov (United States)

    Glucose test - CSF; Cerebrospinal fluid glucose test ... The glucose level in the CSF should be 50 to 80 mg/100 mL (or greater than 2/3 ... Abnormal results include higher and lower glucose levels. Abnormal ... or fungus) Inflammation of the central nervous system Tumor

  1. Brain MRI abnormalities in the adult form of myotonic dystrophy type 1: A longitudinal case series study

    OpenAIRE

    Conforti, Renata; de Cristofaro, Mario; Cristofano, Adriana; Brogna, Barbara; Sardaro, Angela; Tedeschi, Gioacchino; Cirillo, Sossio; Di Costanzo, Alfonso

    2016-01-01

    This study aimed to verify whether brain abnormalities, previously described in patients with myotonic dystrophy type 1 (DM1) by magnetic resonance imaging (MRI), progressed over time and, if so, to characterize their progression. Thirteen DM1 patients, who had at least two MRI examinations, were retrospectively evaluated and included in the study. The mean duration (± standard deviation) of follow-up was 13.4 (±3.8) years, over a range of 7–20 years. White matter lesions (WMLs) were rated by...

  2. Oxidation of [U-13C]glucose in the human brain at 7T under steady state conditions.

    Science.gov (United States)

    Cheshkov, Sergey; Dimitrov, Ivan E; Jakkamsetti, Vikram; Good, Levi; Kelly, Dorothy; Rajasekaran, Karthik; DeBerardinis, Ralph J; Pascual, Juan M; Sherry, A Dean; Malloy, Craig R

    2017-12-01

    Disorders of brain energy metabolism and neurotransmitter recycling have been implicated in multiple neurological conditions. 13 C magnetic resonance spectroscopy ( 13 C MRS) during intravenous administration of 13 C-labeled compounds has been used to measure turnover rates of brain metabolites. This approach, however, requires prolonged infusion inside the magnet. Proton decoupling is typically required but may be difficult to implement with standard equipment. We examined an alternative approach to monitor glucose metabolism in the human brain. 13 C-enriched glucose was infused in healthy subjects outside the magnet to a steady-state level of 13 C enrichment. Subsequently, the subjects were scanned at 7T for 60 min without 1 H decoupling. Metabolic modeling was used to calculate anaplerosis. Biomarkers of energy metabolism and anaplerosis were detected. The glutamate C5 doublet provided information about glucose-derived acetyl-coenzyme A flux into the tricarboxylic acid (TCA) cycle via pyruvate dehydrogenase, and the bicarbonate signal reflected overall TCA cycle activity. The glutamate C1/C5 ratio is sensitive to anaplerosis. Brain 13 C MRS at 7T provides information about glucose oxidation and anaplerosis without the need of prolonged 13 C infusions inside the scanner and without technical challenges of 1 H decoupling, making it a feasible approach for clinical research. Magn Reson Med 78:2065-2071, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  3. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    Science.gov (United States)

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in v

  4. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    Directory of Open Access Journals (Sweden)

    Julie Nemecek

    Full Text Available Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA to amplify abnormal prion protein (PrP(TSE from highly diluted variant Creutzfeldt-Jakob disease (vCJD-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrP(TSE in tissues and blood. Macaque vCJD PrP(TSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA. Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV, a close relative of the bank vole, seeded with macaque vCJD PrP(TSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N. We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrP(TSE. Meadow vole brain (170N/N PrP genotype was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrP(TSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrP(TSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrP(TSE was more permissive than human PrP(TSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrP(TSE from brains of humans and macaques with vCJD. PrP(TSE signals were reproducibly detected by Western blot in dilutions through 10⁻¹² of vCJD-infected 10% brain homogenates. This is the first report showing PrP(TSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect Pr

  5. Cerebral glucose metabolism in long-term survivors of childhood primary brain tumors treated with surgery and radiotherapy

    DEFF Research Database (Denmark)

    Andersen, Preben B.; Krabbe, Katja; Leffers, Anne M.

    2003-01-01

    Delayed structural cerebral sequelae has been reported following cranial radiation therapy (CRT) to children with primary brain tumors, but little is known about potential functional changes. Twenty-four patients were included, diagnosed and treated at a median age of 11 years, and examined after...... a median recurrence free survival of 16 years by MRI and Positron Emission Tomography using the glucose analog 2-18F-fluoro-2-deoxy-D-glucose (18FDG). Three patients were not analyzed further due to diffuse cerebral atrophy, which might be related to previous hydrocephalus. Twenty-one patients were...... evaluable and regional cerebral metabolic rate for glucose (rCMRglc) was estimated in nontumoral brain regions in 12 patients treated with surgery alone and 9 patients treated with both surgery and CRT. Furthermore 10 normal controls matched for age at examination were included. Patients treated with both...

  6. Stability of regional cerebral glucose metabolism in the normal brain measured by positron emission tomography

    International Nuclear Information System (INIS)

    Tyler, J.L.; Strother, S.C.; Zatorre, R.J.; Alivisatos, B.; Worsley, K.J.; Diksic, M.; Yamamoto, Y.L.

    1988-01-01

    Cerebral glucose utilization (LCMRGI) was measured using the [ 18 F]fluorodeoxyglucose method with PET in two groups of ten healthy young volunteers, each scanned in a resting state under different methodological conditions. In addition, five subjects had a second scan within 48 hr. Mean hemispheric values averaged 45.8 +/- 3.3 mumol/100 g/min in the right cerebral hemisphere and 47.0 +/- 3.7 mumol/100 g/min in the left hemisphere. A four-way analysis of variance (group, sex, region, hemisphere) was carried out on the results using three different methods of data manipulation: (a) the raw values of glucose utilization, (b) LCMRGI values normalized by the mean hemispheric gray matter LCMRGI value, and (c) log transformed LCMRGI values. For all analysis techniques, significantly higher LCMRGI values were consistently seen in the left mid and posterior temporal area and caudate nucleus relative to the right, and in the right occipital region relative to the left. The coefficient of variation of intrasubject regional differences (9.9%) was significantly smaller than the coefficient of variation for regions between subjects (16.5%). No differences were noted between the sexes and no effect of repeat procedures was seen in subjects having multiple scans. In addition, inter-regional LCMRGI correlations were examined both in values from the 20 normal subjects, as well as in a set of hypothetical abnormal values. Results were compared with those reported from other PET centers; despite certain methodological differences, the intersubject and inter-regional variation of LCMRGI is fairly constant

  7. Radiation-induced brain structural and functional abnormalities in presymptomatic phase and outcome prediction.

    Science.gov (United States)

    Ding, Zhongxiang; Zhang, Han; Lv, Xiao-Fei; Xie, Fei; Liu, Lizhi; Qiu, Shijun; Li, Li; Shen, Dinggang

    2018-01-01

    Radiation therapy, a major method of treatment for brain cancer, may cause severe brain injuries after many years. We used a rare and unique cohort of nasopharyngeal carcinoma patients with normal-appearing brains to study possible early irradiation injury in its presymptomatic phase before severe, irreversible necrosis happens. The aim is to detect any structural or functional imaging biomarker that is sensitive to early irradiation injury, and to understand the recovery and progression of irradiation injury that can shed light on outcome prediction for early clinical intervention. We found an acute increase in local brain activity that is followed by extensive reductions in such activity in the temporal lobe and significant loss of functional connectivity in a distributed, large-scale, high-level cognitive function-related brain network. Intriguingly, these radiosensitive functional alterations were found to be fully or partially recoverable. In contrast, progressive late disruptions to the integrity of the related far-end white matter structure began to be significant after one year. Importantly, early increased local brain functional activity was predictive of severe later temporal lobe necrosis. Based on these findings, we proposed a dynamic, multifactorial model for radiation injury and another preventive model for timely clinical intervention. Hum Brain Mapp 39:407-427, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

    Directory of Open Access Journals (Sweden)

    Fabienne Krauer

    2017-01-01

    Full Text Available The World Health Organization (WHO stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome (GBS and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality.The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693. We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose-response relationship and specificity, we found that more than half the relevant studies supported

  9. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

    Science.gov (United States)

    Krauer, Fabienne; Riesen, Maurane; Reveiz, Ludovic; Oladapo, Olufemi T; Martínez-Vega, Ruth; Porgo, Teegwendé V; Haefliger, Anina; Broutet, Nathalie J; Low, Nicola

    2017-01-01

    The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose-response relationship and specificity), we found that more than half the relevant studies supported a causal

  10. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain–Barré Syndrome: Systematic Review

    Science.gov (United States)

    Reveiz, Ludovic; Oladapo, Olufemi T.; Martínez-Vega, Ruth; Haefliger, Anina

    2017-01-01

    Background The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain–Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. Methods and Findings The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose–response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose–response relationship and specificity), we found that more than half the

  11. Magnetic resonance imaging in classification of congenital muscular dystrophies with brain abnormalities

    NARCIS (Netherlands)

    van der Knaap, M. S.; Smit, L. M.; Barth, P. G.; Catsman-Berrevoets, C. E.; Brouwer, O. F.; Begeer, J. H.; de Coo, I. F.; Valk, J.

    1997-01-01

    A survey was performed of magnetic resonance imaging (MRI) findings in 21 patients with congenital muscular dystrophy (CMD) with cerebral abnormalities to evaluate the contribution of MRI to the classification of CMD patients. In 5 patients with Walker-Warburg syndrome (WWS), MRI showed

  12. Magnetic resonance imaging in classification of congenital muscular dystrophies with brain abnormalities

    NARCIS (Netherlands)

    vanderKnaap, MS; Smit, LME; Barth, PG; CatsmanBerrevoets, CE; Brouwer, OF; Begeer, JH; deCoo, IFM; Valk, J.

    A survey was performed of magnetic resonance imaging (MRI) findings in 21 patients with congenital muscular dystrophy (QID) with cerebral abnormalities to evaluate the contribution of MRI to the classification of CMD patients. In 5 patients with Walker-Warburg syndrome (WWS), MRI showed

  13. Association of a Guardian's Report of a Child Acting Abnormally With Traumatic Brain Injury After Minor Blunt Head Trauma.

    Science.gov (United States)

    Nishijima, Daniel K; Holmes, James F; Dayan, Peter S; Kuppermann, Nathan

    2015-12-01

    Increased use of computed tomography (CT) in children is concerning owing to the cancer risk from ionizing radiation, particularly in children younger than 2 years. A guardian report that a child is acting abnormally is a risk factor for clinically important traumatic brain injury (ciTBI) and may be a driving factor for CT use in the emergency department. To determine the prevalence of ciTBIs and TBIs in children younger than 2 years with minor blunt head trauma and a guardian report of acting abnormally with (1) no other findings or (2) other concerning findings for TBI. Secondary analysis of a large, prospective, multicenter cohort study that included 43 399 children younger than 18 years with minor blunt head trauma evaluated in 25 emergency departments. The study was conducted on data obtained between June 2004 and September 2006. Data analysis was performed between August 21, 2014, and March 9, 2015. A guardian report that the child was acting abnormally after minor blunt head trauma. The prevalence of ciTBI (defined as death, neurosurgery, intubation for >24 hours, or hospitalization for ≥2 nights in association with TBI on CT imaging) and TBI on CT imaging in children with a guardian report of acting abnormally with (1) no other findings and (2) other concerning findings for TBI. Of 43 399 children in the cohort study, a total of 1297 children had reports of acting abnormally, of whom 411 (31.7%) had this report as their only finding. Reported as percentage (95% CI), 1 of 411 (0.2% [0-1.3%]) had a ciTBI, and 4 TBIs were noted on the CT scans in 185 children who underwent imaging (2.2% [0.6%-5.4%]). In children with reports of acting abnormally and other concerning findings for TBI, 29 of 886 (3.3% [2.2%-4.7%]) had ciTBIs and 66 of 674 (9.8% [7.7%-12.3%]) had TBIs on CT. Clinically important TBIs are very uncommon, and TBIs noted on CT are uncommon in children younger than 2 years with minor blunt head trauma and guardian reports of the child acting

  14. Abnormal baseline brain activity in patients with neuromyelitis optica: A resting-state fMRI study

    International Nuclear Information System (INIS)

    Liu Yaou; Liang Peipeng; Duan Yunyun; Jia Xiuqin; Wang Fei; Yu Chunshui; Qin Wen; Dong Huiqing; Ye Jing; Li Kuncheng

    2011-01-01

    Purpose: Recent immunopathologic and MRI findings suggest that tissue damage in neuromyelitis optica (NMO) is not limited to spinal cord and optic nerve, but also in brain. Baseline brain activity can reveal the brain functional changes to the tissue damages and give clues to the pathophysiology of NMO, however, it has never been explored by resting-state functional MRI (fMRI). We used regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI to investigate how baseline brain activity changes in patients with NMO. Methods: Resting-state fMRIs collected from seventeen NMO patients and seventeen age- and sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration were further explored. Results: Our results showed that NMO patients had significantly decreased ALFF in precuneus, posterior cingulate cortex (PCC) and lingual gyrus; and increased ALFF in middle frontal gyrus, caudate nucleus and thalamus, compared to normal controls. Moderate negative correlations were found between the EDSS and ALFF in the left middle frontal gyrus (r = -0.436, p = 0.040) and the left caudate (r = -0.542, p = 0.012). Conclusion: The abnormal baseline brain activity shown by resting-state fMRI in NMO is relevant to cognition, visual and motor systems. It implicates a complex baseline brain status of both functional impairments and adaptations caused by tissue damages in these systems, which gives clues to the pathophysiology of NMO.

  15. 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.

  16. Abnormal neurological exam findings in individuals with mild traumatic brain injury (mTBI) versus psychiatric and healthy controls.

    Science.gov (United States)

    Silva, Marc A; Donnell, Alison J; Kim, Michelle S; Vanderploeg, Rodney D

    2012-01-01

    In those with a history of mild traumatic brain injury (mTBI), cognitive and emotional disturbances are often misattributed to that preexisting injury. However, causal determinations of current symptoms cannot be conclusively determined because symptoms are often nonspecific to etiology and offer virtually no differential diagnostic value in postacute or chronic phases. This population-based study examined whether the presence of abnormalities during neurological examination would distinguish between mTBI (in the chronic phase), healthy controls, and selected psychiatric conditions. Retrospective analysis of data from 4462 community-dwelling Army veterans was conducted. Diagnostically unique groups were compared on examination of cranial nerve function and other neurological signs. Results demonstrated that individuals with mTBI were no more likely than those with a major depressive disorder, generalized anxiety disorder, posttraumatic stress disorder, or somatoform disorder to show any abnormality. Thus, like self-reported cognitive and emotional symptoms, the presence of cranial nerve or other neurological abnormalities offers no differential diagnostic value. Clinical implications and study limitations are presented.

  17. Brain abnormalities underlying limb apraxia in corticobasal degeneration: an fMRI study

    Science.gov (United States)

    Beauchet, Olivier; Giraux, Pascal; Schneider, Fabien; Peyron, Roland; Barral, Fabrice; Laurent, Bernard

    2001-01-01

    Corticobasal degeneration is a neurodegenerative disease characterized, by cortical dysfunction and extrapyramidal signs. The most consistent symptom is a unilateral limb apraxia, which consists of an isolated disorder of gestural production involving primarily the upper limb. The objective of this study is to investigate the functional abnormalities that may underlie motor dysfunction, and those which might correlate to the severity of limb apraxia. PMID:22034043

  18. Tinnitus perception and distress is related to abnormal spontaneous brain activity as measured by magnetoencephalography.

    Directory of Open Access Journals (Sweden)

    2005-06-01

    Full Text Available BACKGROUND: The neurophysiological mechanisms underlying tinnitus perception are not well understood. Surprisingly, there have been no group studies comparing abnormalities in ongoing, spontaneous neuronal activity in individuals with and without tinnitus perception. METHODS AND FINDINGS: Here, we show that the spontaneous neuronal activity of a group of individuals with tinnitus (n = 17 is characterised by a marked reduction in alpha (8-12 Hz power together with an enhancement in delta (1.5-4 Hz as compared to a normal hearing control group (n = 16. This pattern was especially pronounced for temporal regions. Moreover, correlations with tinnitus-related distress revealed strong associations with this abnormal spontaneous activity pattern, particularly in right temporal and left frontal areas. Overall, effects were stronger for the alpha than for the delta frequency band. A data stream of 5 min, recorded with a whole-head neuromagnetometer under a resting condition, was sufficient to extract the marked differences. CONCLUSIONS: Despite some limitations, there are arguments that the regional pattern of abnormal spontaneous activity we found could reflect a tinnitus-related cortical network. This finding, which suggests that a neurofeedback approach could reduce the adverse effects of this disturbing condition, could have important implications for the treatment of tinnitus.

  19. Abnormal brain white matter network in young smokers: a graph theory analysis study.

    Science.gov (United States)

    Zhang, Yajuan; Li, Min; Wang, Ruonan; Bi, Yanzhi; Li, Yangding; Yi, Zhang; Liu, Jixin; Yu, Dahua; Yuan, Kai

    2018-04-01

    Previous diffusion tensor imaging (DTI) studies had investigated the white matter (WM) integrity abnormalities in some specific fiber bundles in smokers. However, little is known about the changes in topological organization of WM structural network in young smokers. In current study, we acquired DTI datasets from 58 male young smokers and 51 matched nonsmokers and constructed the WM networks by the deterministic fiber tracking approach. Graph theoretical analysis was used to compare the topological parameters of WM network (global and nodal) and the inter-regional fractional anisotropy (FA) weighted WM connections between groups. The results demonstrated that both young smokers and nonsmokers had small-world topology in WM network. Further analysis revealed that the young smokers exhibited the abnormal topological organization, i.e., increased network strength, global efficiency, and decreased shortest path length. In addition, the increased nodal efficiency predominately was located in frontal cortex, striatum and anterior cingulate gyrus (ACG) in smokers. Moreover, based on network-based statistic (NBS) approach, the significant increased FA-weighted WM connections were mainly found in the PFC, ACG and supplementary motor area (SMA) regions. Meanwhile, the network parameters were correlated with the nicotine dependence severity (FTND) scores, and the nodal efficiency of orbitofrontal cortex was positive correlation with the cigarette per day (CPD) in young smokers. We revealed the abnormal topological organization of WM network in young smokers, which may improve our understanding of the neural mechanism of young smokers form WM topological organization level.

  20. Abnormal brain activation during movement observation in patients with conversion paralysis.

    Science.gov (United States)

    Burgmer, Markus; Konrad, Carsten; Jansen, Andreas; Kugel, Harald; Sommer, Jens; Heindel, Walter; Ringelstein, Erich B; Heuft, Gereon; Knecht, Stefan

    2006-02-15

    Dissociative paralysis in conversion disorders has variably been attributed to a lack of movement initiation or an inhibition of movement. While psychodynamic theory suggests altered movement conceptualization, brain activation associated with observation and replication of movements has so far not been assessed neurobiologically. Here, we measured brain activation by functional magnetic resonance imaging during observation and subsequent imitative execution of movements in four patients with dissociative hand paralysis. Compared to healthy controls conversion disorder patients showed decreased activation of cortical hand areas during movement observation. This effect was specific to the side of their dissociative paralysis. No brain activation compatible with movement inhibition was observed. These findings indicate that in dissociative paralysis, there is not only derangement of movement initiation but already of movement conceptualization. This raises the possibility that strategies targeted at reestablishing appropriate movement conceptualization may contribute to the therapy of dissociative paralysis.

  1. Abnormalities of Microcirculation and Intracranial and Cerebral Perfusion Pressures in Severe Brain Injury

    Directory of Open Access Journals (Sweden)

    Yu. A. Churlyaev

    2008-01-01

    Full Text Available Objective: to evaluate the states of microcirculation, cerebral perfusion intracranial pressures in patients with isolated severe brain injury (SBI and to determine their possible relationships. Subjects and methods. 148 studies were performed in 16 victims with SBI. According to the outcome of brain traumatic disease, the patients were divided into two groups: 1 those who had a good outcome (n=8 and 2 those who had a fatal outcome (n=8. Microcirculation was examined by skin laser Doppler flowmetry using a LAKK-01 capillary blood flow laser analyzer (LAZMA Research-and-Production Association, Russian Federation. All the victims underwent surgical interventions to remove epi-, subdural, and intracerebral hematomas. A Codman subdural/intraparenchymatous intracranial pressure (ICD sensor (Johnson & Johnson, United Kingdom was intraoperatively inserted in the victims. Cerebral perfusion pressure (CPP was calculated using the generally accepted formula: CPP = MBP (mean blood pressure — ICD. ICD, CPP, and microcirculation were studied on postoperative days 1, 3, 5, and 7. Their values were recorded simultaneously. Ninety and 58 studies were conducted in the group of patients with good and fatal outcomes, respectively. Results. No correlation between the changes in MBP, ICD, and microcirculatory parameters suggested that the value of ICD was determined by the nature of brain damage and it was the leading and determining indicator in the diagnosis and treatment of secondary cerebral lesions. The amplitude of low-frequency fluctuations directly correlated with ICD, which indicated that they might be used to evaluate cerebral perfusion and impaired cerebral circulation indirectly in victims with severe brain injury. Conclusion. The laser Doppler flowmetric technique makes it possible not only to qualitatively, but also quantitatively determine changes in the tissue blood flow system in severe brain injury. With this technique, both the local and central

  2. 3D PATTERN OF BRAIN ABNORMALITIES IN WILLIAMS SYNDROME VISUALIZED USING TENSOR-BASED MORPHOMETRY

    Science.gov (United States)

    Chiang, Ming-Chang; Reiss, Allan L.; Lee, Agatha D.; Bellugi, Ursula; Galaburda, Albert M.; Korenberg, Julie R.; Mills, Debra L.; Toga, Arthur W.; Thompson, Paul M.

    2009-01-01

    Williams syndrome (WS) is a neurodevelopmental disorder associated with deletion of ~20 contiguous genes in chromosome band 7q11.23. Individuals with WS exhibit mild to moderate mental retardation, but are relatively more proficient in specific language and musical abilities. We used tensor-based morphometry (TBM) to visualize the complex pattern of gray/white matter reductions in WS, based on fluid registration of structural brain images. Methods 3D T1-weighted brain MRIs of 41 WS subjects (age: 29.2±9.2SD years; 23F/18M) and 39 age-matched healthy controls (age: 27.5±7.4 years; 23F/16M) were fluidly registered to a minimum deformation target. Fine-scale volumetric differences were mapped between diagnostic groups. Local regions were identified where regional structure volumes were associated with diagnosis, and with intelligence quotient (IQ) scores. Brain asymmetry was also mapped and compared between diagnostic groups. Results WS subjects exhibited widely distributed brain volume reductions (~10–15% reduction; P < 0.0002, permutation test). After adjusting for total brain volume, the frontal lobes, anterior cingulate, superior temporal gyrus, amygdala, fusiform gyrus and cerebellum were found to be relatively preserved in WS, but parietal and occipital lobes, thalamus and basal ganglia, and midbrain were disproportionally decreased in volume (P < 0.0002). These regional volumes also correlated positively with performance IQ in adult WS subjects (age ≥ 30 years, P = 0.038). Conclusion TBM facilitates 3D visualization of brain volume reductions in WS. Reduced parietal/occipital volumes may be associated with visuospatial deficits in WS. By contrast, frontal lobes, amygdala, and cingulate gyrus are relatively preserved or even enlarged, consistent with unusual affect regulation and language production in WS. PMID:17512756

  3. Role of NMDA receptors in the increase of glucose metabolism in the rat brain induced by fluorocitrate.

    Science.gov (United States)

    Hirose, Shinichiro; Umetani, Yukiko; Amitani, Misato; Hosoi, Rie; Momosaki, Sotaro; Hatazawa, Jun; Gee, Antony; Inoue, Osamu

    2007-03-30

    The effect of inhibition of glial metabolism by infusion of fluorocitrate (FC, 1 nmol/microl, 2 microl) into the right striatum of the rat brain on the glucose metabolism was studied. Significant increases in [(18)F]fluorodeoxyglucose ([(18)F]FDG) uptake (45 min) in the right cerebral cortex and striatum were observed 4h after the infusion of FC, both as determined by the tissue dissection method and autoradiography. No significant increase in the initial uptake of [(18)F]FDG (1 min) was seen in the striatum. Pretreatment with dizocilpine (MK-801), an N-methyl-d-aspartate (NMDA) receptor antagonist, reduced [(18)F]FDG uptake in not only FC infused hemisphere but also in the contralateral hemisphere (saline-infused side). The radioactivity concentrations in plasma at 1, 5 and 45 min after the [(18)F]FDG injection were not altered by MK-801. This effect of MK-801 on glucose metabolism observed in the rat brain infused with FC was different from previous reports which indicated an increase in glucose metabolism in some areas of normal rat brain. In addition, the enhancement of glucose metabolism in the striatum induced by FC was almost completely abolished by pretreatment with MK-801. In the cerebral cortex, the relative ratio of radioactivity concentration in the right hemisphere to that in the left hemisphere still remained 1.37 (tissue dissection method) or 1.55 (autoradiography), which indicated that MK-801 partially blocked the effect of FC of enhancing glucose metabolism in this region. These results indicate an important role of NMDA-mediated signal transmission on the increase of glucose utilization induced by inhibition of glial metabolism.

  4. Structural brain abnormalities in women with subclinical depression, as revealed by voxel-based morphometry and diffusion tensor imaging.

    Science.gov (United States)

    Hayakawa, Yayoi K; Sasaki, Hiroki; Takao, Hidemasa; Mori, Harushi; Hayashi, Naoto; Kunimatsu, Akira; Aoki, Shigeki; Ohtomo, Kuni

    2013-01-25

    Brain structural changes accompany major depressive disorder, but whether subclinical depression is accompanied by similar changes in brain volume and white matter integrity is unknown. By using voxel-based morphometry (VBM) of the gray matter and tract-specific analysis based on diffusion tensor imaging (DTI) of the white matter, we explored the extent to which abnormalities could be identified in specific brain structures of healthy adults with subclinical depression. The subjects were 21 community-dwelling adults with subclinical depression, as measured by their Center for Epidemiologic Studies Depression Scale (CES-D) scores. They were not demented and had no neurological or psychiatric history. We collected brain magnetic resonance images of the patients and of 21 matched control subjects, and we used VBM to analyze the differences in regional gray matter volume between the two groups. Moreover, we examined the white matter integrity by using tract-specific analysis based on the gray matter volume changes revealed by VBM. VBM revealed that the volumes of both anterior cingulate gyri and the right rectal gyrus were smaller in subclinically depressed women than in control women. Calculation of DTI measures in the anterior cingulum bundle revealed a positive correlation between CES-D scale score and radial diffusivity in the right anterior cingulum in subclinically depressed women. The small sample size limits the stability of the reported findings. Gray matter volume reduction and white matter integrity change in specific frontal brain regions may be associated with depressive symptoms in women, even at a subclinical level. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Overlapping and Segregating Structural Brain Abnormalities in Twins With Schizophrenia or Bipolar Disorder

    NARCIS (Netherlands)

    Pol, Hilleke E. Hulshoff; van Baal, G. Caroline M.; Schnack, Hugo G.; Brans, Rachel G. H.; van der Schot, Astrid C.; Brouwer, Rachel M.; van Haren, Neeltje E. M.; Lepage, Claude; Collins, D. Louis; Evans, Alan C.; Boomsma, Dorret I.; Nolen, Willem; Kahn, Rene S.

    Context: The nosologic dichotomy between schizophrenia and bipolar disorder (BD) as formulated by Kraepelin is currently being questioned, stimulated by the finding that schizophrenia and BD partly share a common genetic origin. Although both disorders are characterized by changes in brain

  6. MR Spectroscopy evaluation of white matter signal abnormalities of different non-neoplastic brain lesions

    Directory of Open Access Journals (Sweden)

    Randa O. Kaddah

    2016-03-01

    Conclusion: MRS is a noninvasive additional MRI technique to define the nature of non-neoplastic brain lesions. Together with image analysis, it may be the key to etiologic diagnosis or, at least, definition of the group where the lesion is classified, by detecting changes in different metabolites and peaks of inflammation.

  7. Co-Localisation of Abnormal Brain Structure and Function in Specific Language Impairment

    Science.gov (United States)

    Badcock, Nicholas A.; Bishop, Dorothy V. M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior…

  8. Brief Report: Abnormal Association between the Thalamus and Brain Size in Asperger's Disorder

    Science.gov (United States)

    Hardan, Antonio Y.; Girgis, Ragy R.; Adams, Jason; Gilbert, Andrew R.; Melhem, Nadine M.; Keshavan, Matcheri S.; Minshew, Nancy J.

    2008-01-01

    The objective of this study was to examine the relationship between thalamic volume and brain size in individuals with Asperger's disorder (ASP). Volumetric measurements of the thalamus were performed on MRI scans obtained from 12 individuals with ASP (age range: 10-35 years) and 12 healthy controls (age range: 9-33 years). A positive correlation…

  9. Abnormal hemodynamic response to forepaw stimulation in rat brain after cocaine injection

    Science.gov (United States)

    Chen, Wei; Park, Kicheon; Choi, Jeonghun; Pan, Yingtian; Du, Congwu

    2015-03-01

    Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine's effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.

  10. Inconsistency in Abnormal Brain Activity across Cohorts of ADHD-200 in Children with Attention Deficit Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Jian-Bao Wang

    2017-06-01

    Full Text Available Many papers have shown results from the multi-site dataset of resting-state fMRI (rs-fMRI in attention deficit hyperactivity disorder (ADHD, a data-sharing project named ADHD-200. However, few studies have illustrated that to what extent the pooled findings were consistent across cohorts. The present study analyzed three voxel-wise whole-brain metrics, i.e., amplitude of low-frequency fluctuation (ALFF, regional homogeneity (ReHo, and degree centrality (DC based on the pooled dataset as well as individual cohort of ADHD-200. In addition to the conventional frequency band of 0.01–0.08 Hz, sub-frequency bands of 0–0.01, 0.01–0.027, 0.027–0.073, 0.073–0.198, and 0.198–0.25 Hz, were assessed. While the pooled dataset showed abnormal activity in some brain regions, e.g., the bilateral sensorimotor cortices, bilateral cerebellum, and the bilateral lingual gyrus, these results were highly inconsistent across cohorts, even across the three cohorts from the same research center. The standardized effect size was rather small. These findings suggested a high heterogeneity of spontaneous brain activity in ADHD. Future studies based on multi-site large-sample dataset should be performed on pooled data and single cohort data, respectively and the effect size must be shown.

  11. Left ventricular mass-geometry and silent cerebrovascular disease: The Cardiovascular Abnormalities and Brain Lesions (CABL) study.

    Science.gov (United States)

    Nakanishi, Koki; Jin, Zhezhen; Homma, Shunichi; Elkind, Mitchell S V; Rundek, Tatjana; Tugcu, Aylin; Yoshita, Mitsuhiro; DeCarli, Charles; Wright, Clinton B; Sacco, Ralph L; Di Tullio, Marco R

    2017-03-01

    Although abnormal left ventricular geometric patterns have prognostic value for morbidity and mortality, their possible association with silent cerebrovascular disease has not been extensively evaluated. We examined 665 participants in the CABL study who underwent transthoracic echocardiography and brain magnetic resonance imaging. Participants were divided into 4 geometric patterns: normal geometry (n=397), concentric remodeling (n=89), eccentric hypertrophy (n=126), and concentric hypertrophy (n=53). Subclinical cerebrovascular disease was defined as silent brain infarcts (SBIs) and white matter hyperintensity volume (WMHV; expressed as log-transformed percentage of the total cranial volume). Silent brain infarcts were observed in 94 participants (14%). Mean log-WMHV was -0.97±0.93. Concentric hypertrophy carried the greatest risk for both SBI (adjusted odds ratio [OR] 3.39, Pdisease. In subgroup analyses, concentric and eccentric hypertrophies were significantly associated with SBI and WMHV in both genders and nonobese participants, but differed for SBI by age (all ages for eccentric hypertrophy, only patients ≥70years for concentric hypertrophy) and by race-ethnicity (Hispanics for eccentric hypertrophy, blacks for concentric hypertrophy; no association in whites). Left ventricular hypertrophy, with both eccentric and concentric patterns, was significantly associated with subclinical cerebrovascular disease in a multiethnic stroke-free general population. Left ventricular geometric patterns may carry different risks for silent cerebrovascular disease in different sex, age, race-ethnic, and body size subgroups. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Absence of PTHrP nuclear localization and carboxyl terminus sequences leads to abnormal brain development and function.

    Directory of Open Access Journals (Sweden)

    Zhen Gu

    Full Text Available We assessed whether the nuclear localization sequences (NLS and C terminus of parathyroid hormone-related protein (PTHrP play critical roles in brain development and function. We used histology, immunohistochemistry, histomorphometry, Western blots and electrophysiological recordings to compare the proliferation and differentiation of neural stem cells, neuronal hippocampal synaptic transmission, and brain phenotypes including shape and structures, in Pthrp knock-in mice, which express PTHrP (1-84, a truncated form of the protein that is missing the NLS and the C-terminal region of the protein, and their wild-type littermates. Results showed that Pthrp knock-in mice display abnormal brain shape and structures; decreased neural cell proliferative capacity and increased apoptosis associated with up-regulation of cyclin dependent kinase inhibitors p16, p21, p27 and p53 and down-regulation of the Bmi-1 oncogene; delayed neural cell differentiation; and impaired hippocampal synaptic transmission and plasticity. These findings provide in vivo experimental evidence that the NLS and C-terminus of PTHrP are essential not only for the regulation of neural cell proliferation and differentiation, but also for the maintenance of normal neuronal synaptic transmission and plasticity.

  13. Resting-state functional MRI of abnormal baseline brain activity in young depressed patients with and without suicidal behavior.

    Science.gov (United States)

    Cao, Jun; Chen, Xiaorong; Chen, Jianmei; Ai, Ming; Gan, Yao; Wang, Wo; Lv, Zhen; Zhang, Shuang; Zhang, Shudong; Wang, Suya; Kuang, Li; Fang, Weidong

    2016-11-15

    Suicide among youth is a major public health challenge, attracting increasing attention. However, the neurobiological mechanisms and the pathophysiology underlying suicidal behavior in depressed youths are still unclear. The fMRI enables a better understanding of functional changes in the brains of young suicide attempters with depressive disorder through detecting spontaneous neural activity. The purpose of this study was to identify the relationship between abnormalities involving local brain function and suicidal attempts in depressed youths using resting-state fMRI (RS-fMRI). Thirty-five depressed youths aged between 15 and 29 years with a history of suicidal attempts (SU group), 18 patients without suicidal attempts (NSU group) and 47 gender-, age- and education-matched healthy controls (HC) underwent psychological assessment and R-fMRI. The differences in fractional amplitude of low-frequency fluctuation (ALFF) among the three groups were compared. The clinical factors correlated with z-score ALFF in the regions displaying significant group differences were investigated. The ROC method was used to evaluate these clusters as markers to screen patients with suicidal behavior. Compared with the NSU and HC groups, the SU group showed increased zALFF in the right superior temporal gyrus (r-STG), left middle temporal gyrus (L-MTG) and left middle occipital gyrus (L-MOG). Additionally, significantly decreased zALFF values in the L-SFG and L-MFG were found in the SU group compared with the NSU group, which were negatively correlated with BIS scores in the SU group. Further ROC analysis revealed that the mean zALFF values in these two regions (sensitivity=83.3% and specificity=71.4%) served as markers to differentiate the two patient subtypes. The SU group had abnormal spontaneous neural activity during the resting state, and decreased activity in L-SFG and L-MFG was associated with increased impulsivity in SU group. Our results suggested that abnormal neural activity

  14. No abnormalities of intrinsic brain connectivity in the interictal phase of migraine with aura

    DEFF Research Database (Denmark)

    Hougaard, Anders; Amin, F M; Magon, S

    2015-01-01

    BACKGROUND AND PURPOSE: Functional neuroimaging studies have shown hyperresponsiveness of cortical areas to visual stimuli in migraine patients with aura outside of attacks. This may be a key feature in the initiation of aura episodes and possibly also migraine headache attacks. It is unknown...... if cortical dysfunction is present at rest, i.e. in the absence of any external stimuli. Functional magnetic resonance imaging is a powerful technique for evaluating resting state functional connectivity, i.e. coherence of brain activity across cerebral areas. The objective of this study was to investigate...... resting-state functional brain connectivity in migraineurs with aura outside of attacks using functional magnetic resonance imaging. METHODS: Forty patients suffering from migraine with visual aura and 40 individually age and gender matched healthy controls with no history or family history of migraine...

  15. Demonstration of cerebral abnormalities in cocaine abusers with SPECT perfusion brain scans

    International Nuclear Information System (INIS)

    Nagel, J.S.; Tumeh, S.S.; English, R.J.; Moore, M.; Lee, V.W.; Holman, L.B.

    1989-01-01

    This paper reports I-123 isopropyl iodoamphetamine (IMP) single-photon emission CT (SPECT) brain scans performed on cocaine users to investigate the effects of cocaine on the cerebral perfusion in a manner similar to previous CT, angiographic and positron-emission tomographic (PET) studies. Ten asymptomatic or mildly symptomatic cocaine users, two users with major neurovascular complications, and five normal subjects were studied with IMP SPECT. Rotating-brain images of the cerebral IMP uptake were displayed by using a distance-weighted surface-projection technique and were visually analyzed for focal cortical perfusion deficits. Eleven cocaine users had multiple scattered cortical IMP defects. Frontal lobe defects were most prominent. One user had confluent defects resembling swiss cheese. Concurrent CT scans available in nine patients were negative in seven and showed infarcts in two. No similar focal findings were visible in normals

  16. 3D PATTERN OF BRAIN ABNORMALITIES IN WILLIAMS SYNDROME VISUALIZED USING TENSOR-BASED MORPHOMETRY

    OpenAIRE

    Chiang, Ming-Chang; Reiss, Allan L.; Lee, Agatha D.; Bellugi, Ursula; Galaburda, Albert M.; Korenberg, Julie R.; Mills, Debra L.; Toga, Arthur W.; Thompson, Paul M.

    2007-01-01

    Williams syndrome (WS) is a neurodevelopmental disorder associated with deletion of ~20 contiguous genes in chromosome band 7q11.23. Individuals with WS exhibit mild to moderate mental retardation, but are relatively more proficient in specific language and musical abilities. We used tensor-based morphometry (TBM) to visualize the complex pattern of gray/white matter reductions in WS, based on fluid registration of structural brain images.

  17. Abnormalities in Human Brain Creatine Metabolism in Gulf War Illness Probed with MRS

    Science.gov (United States)

    2013-10-01

    and Brain Sciences Board Chair Debbie Francis Board Vice Chair Bob Wilbur Founding Chair Shelia Schlosberg Leadership Council Sallie and...Frederic Asche, Jr. Claud ia and Dennis Berman Toni C. Brinker Jean Ann Brock Dianne Cash Cullum Clark Mary Anne Cree Teresa and David Disiere...Boone Pickens Terry and Bob Rowling Annette and Harold Simmons Jane and Bud Smith Jill Smith Claudia and Gerald Stool Dee and Charles Wyly The

  18. Brain Abnormalities in Congenital Fibrosis of the Extraocular Muscles Type 1: A Multimodal MRI Imaging Study.

    Science.gov (United States)

    Miao, Wen; Man, Fengyuan; Wu, Shaoqin; Lv, Bin; Wang, Zhenchang; Xian, Junfang; Sabel, Bernhard A; He, Huiguang; Jiao, Yonghong

    2015-01-01

    To explore the possible brain structural and functional alterations in congenital fibrosis of extraocular muscles type 1 (CFEOM1) patients using multimodal MRI imaging. T1-weighted, diffusion tensor images and functional MRI data were obtained from 9 KIF21A positive patients and 19 age- and gender-matched healthy controls. Voxel based morphometry and tract based spatial statistics were applied to the T1-weighted and diffusion tensor images, respectively. Amplitude of low frequency fluctuations and regional homogeneity were used to process the functional MRI data. We then compared these multimodal characteristics between CFEOM1 patients and healthy controls. Compared with healthy controls, CFEOM1 patients demonstrated increased grey matter volume in bilateral frontal orbital cortex and in the right temporal pole. No diffusion indices changes were detected, indicating unaffected white matter microstructure. In addition, from resting state functional MRI data, trend of amplitude of low-frequency fluctuations increases were noted in the right inferior parietal lobe and in the right frontal cortex, and a trend of ReHo increase (pabnormality of extraocular muscles and their innervating nerves. Future studies should consider the possible correlations between brain morphological/functional findings and clinical data, especially pertaining to eye movements, to obtain more precise answers about the role of brain area changes and their functional consequence in CFEOM1.

  19. Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth.

    Directory of Open Access Journals (Sweden)

    Olga Kapellou

    2006-08-01

    Full Text Available We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment.We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25-1.33, which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001 independent of intrauterine or postnatal somatic growth.Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery.

  20. Adolescent binge drinking linked to abnormal spatial working memory brain activation: differential gender effects.

    Science.gov (United States)

    Squeglia, Lindsay M; Schweinsburg, Alecia Dager; Pulido, Carmen; Tapert, Susan F

    2011-10-01

    Binge drinking is prevalent during adolescence, and its effect on neurocognitive development is of concern. In adult and adolescent populations, heavy substance use has been associated with decrements in cognitive functioning, particularly on tasks of spatial working memory (SWM). Characterizing the gender-specific influences of heavy episodic drinking on SWM may help elucidate the early functional consequences of drinking on adolescent brain functioning. Forty binge drinkers (13 females, 27 males) and 55 controls (24 females, 31 males), aged 16 to 19 years, completed neuropsychological testing, substance use interviews, and an SWM task during functional magnetic resonance imaging. Significant binge drinking status × gender interactions were found (p working memory performances (p effects of heavy alcohol use during adolescence, while males may be more resilient to the deleterious effects of binge drinking. Future longitudinal research will examine the significance of SWM brain activation as an early neurocognitive marker of alcohol impact to the brain on future behaviors, such as driving safety, academic performance, and neuropsychological performance. Copyright © 2011 by the Research Society on Alcoholism.

  1. Brain abnormalities among the mentally retarded prenatally exposed atomic bomb survivors

    International Nuclear Information System (INIS)

    Schull, W.J.; Otake, Masanori; Nishitani, Hiromu; Hasuo, Kanehiro; Kobayashi, Takuro; Goto, Ikuo.

    1992-07-01

    An increased occurrence of severe mental retardation, with or without accompanying small head size, at specific gestational ages has been the most conspicuous effect on brain development of prenatal exposure to the bombings of Hiroshima and Nagasaki. A variety of biological mechanisms could be responsible for this finding, including cell killing and mismanaged neuronal migration. We describe here the findings on magnetic resonance imaging of the brains of five of these mentally retarded individuals, all of whom were exposed in the 8th through the 15th weeks following fertilization, the gestational period shown to be the most vulnerable to radiation-related damage. In the two cases exposed at the 8th or 9th week following fertilization, large areas of ectopic gray matter are seen, strong evidence of a failure of the neurons to migrate to their proper functional sites. The two individuals exposed in the 12th or 13th week show no readily recognized ectopic gray areas but do show mild macrogyria, which implies some impairment in the development of the cortical zone. Moreover, both have mega cisterna magna. Finally, the one individual seen who was exposed still later in development, in the 15th week, shows none of the changes seen in the other four individuals. This person's brain, though small, appears to have normal architecture. These findings are discussed in terms of the embryological events transpiring at the time of the prenatal exposure of these individuals to ionizing radiation. (author)

  2. Differential impact of hyponatremia and hepatic encephalopathy on health-related quality of life and brain metabolite abnormalities in cirrhosis.

    Science.gov (United States)

    Ahluwalia, Vishwadeep; Wade, James B; Thacker, Leroy; Kraft, Kenneth A; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Bouneva, Iliana; Puri, Puneet; Luketic, Velimir; Sanyal, Arun J; Gilles, Hochong; Heuman, Douglas M; Bajaj, Jasmohan S

    2013-09-01

    Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality of life (HRQOL) and cognition in cirrhosis. We aimed at studying the effect of hyponatremia on cognition, HRQOL, and brain MR spectroscopy (MRS) independent of HE. Four cirrhotic groups (no HE/HN, HE alone, HN alone (sodium Impact Profile (SIP: higher score is worse; has psychosocial and physical sub-scores) and brain MRS (myoinositol (mI) and glutamate+glutamine (Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. 82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN, and 10 HN, MELD 12, 63% hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN: 3, HN: 3.5, HE: 6.5, HE+HN: 7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP (p<0.0001, all comparisons). Brain MRS showed the lowest Glx in HN and the highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE, HE+HN, and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psychosocial SIP scores. Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  3. Three-dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using tensor-based morphometry.

    Science.gov (United States)

    Gogtay, Nitin; Lu, Allen; Leow, Alex D; Klunder, Andrea D; Lee, Agatha D; Chavez, Alex; Greenstein, Deanna; Giedd, Jay N; Toga, Arthur W; Rapoport, Judith L; Thompson, Paul M

    2008-10-14

    Earlier studies revealed progressive cortical gray matter (GM) loss in childhood-onset schizophrenia (COS) across both lateral and medial surfaces of the developing brain. Here, we use tensor-based morphometry to visualize white matter (WM) growth abnormalities in COS throughout the brain. Using high-dimensional elastic image registration, we compared 3D maps of local WM growth rates in COS patients and healthy children over a 5-year period, based on analyzing longitudinal brain MRIs from 12 COS patients and 12 healthy controls matched for age, gender, and scan interval. COS patients showed up to 2.2% slower growth rates per year than healthy controls in WM (P = 0.02, all P values corrected). The greatest differences were in the right hemisphere (P = 0.006). This asymmetry was attributable to a right slower than left hemisphere growth rate mapped in COS patients (P = 0.037) but not in healthy controls. WM growth rates reached 2.6% per year in healthy controls (P = 0.0002). COS patients showed only a 1.3% per year trend for growth in the left hemisphere (P = 0.066). In COS, WM growth rates were associated with improvement in the Children's Global Assessment Scale (R = 0.64, P = 0.029). Growth rates were reduced throughout the brain in COS, but this process appeared to progress in a front-to-back (frontal-parietal) fashion, and this effect was not attributable to lower IQ. Growth rates were correlated with functional prognosis and were visualized as detailed 3D maps. Finally, these findings also confirm that the progressive GM deficits seen in schizophrenia are not the result of WM overgrowth.

  4. Decreased labeling of amino acids by inhibition of the utilization of [3H, 14C]glucose via the hexosemonophosphate shunt in rat brain in vivo

    International Nuclear Information System (INIS)

    Gaitonde, M.K.; James, M.D.; Evans, G.M.

    1984-01-01

    Treatment of rats with 6-aminonicotinamide showed a small but significant decrease in the labeling of amino acids in the brain after injection of [ 3 H]acetate. The results of these experiments also gave evidence of the presence of [ 3 H]glucose and [ 3 H]acetate, and an increase in [ 3 H]glucose content in the brain of 6-aminonicotinamide treated rats. To apportion the contribution of [ 3 H]glucose formed by gluconeogenesis from [ 3 H]acetate to the labeling of amino acids a method was formulated based on the measurement of radioactivity of amino acids, lactate and free sugars in brain after injection of [6- 3 H]glucose or [1- 3 H]glucose relative to that after co-injection of [U- 14 C]glucose or [2- 14 C]glucose. These findings indicated that a significant decrease in the labeling of amino acids from [U-14C]glucose reported previously and again confirmed using [1- 3 H], [6- 3 H], [2- 14 C] or [U- 14 C]glucose in the present investigation was not due to the inhibition of the activities of enzymes of the citric acid cycle. These results support the postulated role of the hexosemonophosphate shunt for the utilization of glucose in providing neurotransmitter amino acids glutamate and gamma-aminobutyrate

  5. Structural connectivity analysis reveals abnormal brain connections in agenesis of the corpus callosum in children.

    Science.gov (United States)

    Meoded, Avner; Katipally, Rohan; Bosemani, Thangamadhan; Huisman, Thierry A G M; Poretti, Andrea

    2015-05-01

    Structural connectivity analysis is an ideal tool to study connections in brain malformations. We aimed to characterize the topological network measures and study sub-networks in children with agenesis of the corpus callosum (AgCC). We hypothesized a more segregated structural network in children with AgCC. Structural connectivity analysis including topology analysis and network-based-statistics was applied in children with AgCC and age-matched controls. Probabilistic-tractography and brain segmentation into 108 regions were performed. For controls, structural connectivity has been analyzed after excluding the callosal connections ('virtual callosotomy'). Ten patients (six males, mean age 6.5 years, SD 4.5 years) and ten controls (mean age 5.9 years, SD 4.7 years) were included. In patients, topology analysis revealed higher clustering coefficient and transitivity and lower small world index and assortativity compared to controls. The bilateral insula were identified as hubs in patients, whereas the cerebellum was detected as a hub only in controls. Three sub-networks of increased connectivity were identified in patients. We found reduced global and increased local connectivity in children with AgCC compared to controls. Neural plasticity in AgCC may attempt to increase the interhemispheric connectivity through alternative decussating pathways other than the corpus callosum. • The structural connectivity analysis quantifies white-matter networks within the brain • In callosal agenesis there is reduced global and increased local connectivity • In callosal agenesis, alternative decussating pathways are used for interhemispheric connectivity.

  6. Apathy is associated with white matter abnormalities in anterior, medial brain regions in persons with HIV infection

    Science.gov (United States)

    Kamat, Rujvi; Brown, Gregory G.; Bolden, Khalima; Fennema-Notestine, Christine; Archibald, Sarah; Marcotte, Thomas D.; Letendre, Scott L.; Ellis, Ronald J.; Woods, Steven Paul; Grant, Igor; Heaton, Robert K.

    2015-01-01

    Apathy is a relatively common psychiatric syndrome in HIV infection, but little is known about its neural correlates. In the present study, we examined the associations between apathy and diffusion tensor imaging (DTI) indices in key frontal white matter regions in the thalamocorticostriatal circuit that has been implicated in the expression of apathy. Nineteen participants with HIV infection and 19 demographically comparable seronegative comparison subjects completed the Apathy subscale of the Frontal Systems Behavioral Scale as a part of a comprehensive neuropsychiatric research evaluation. When compared to the seronegative participants, the HIV+ group had significantly more frontal white matter abnormalities. Within HIV+ persons, and as predicted, higher ratings of apathy were associated with greater white matter alterations in the anterior corona radiata, genu, and orbital medial prefrontal cortex. The associations between white matter alterations and apathy were independent of depression and were stronger among participants with lower current CD4 counts. All told, these findings indicate that apathy is independently associated with white matter abnormalities in anterior, medial brain regions in persons infected with HIV, particularly in the setting of lower current immune functioning, which may have implications for antiretroviral therapy. PMID:25275424

  7. Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

    Science.gov (United States)

    Adams, Hugo Ja; de Klerk, John Mh; Fijnheer, Rob; Heggelman, Ben Gf; Dubois, Stefan V; Nievelstein, Rutger Aj; Kwee, Thomas C

    2016-06-01

    There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI. © The Foundation Acta Radiologica 2015.

  8. Brain structure abnormalities in first-episode psychosis patients with persistent apathy.

    Science.gov (United States)

    Mørch-Johnsen, Lynn; Nesvåg, Ragnar; Faerden, Ann; Haukvik, Unn K; Jørgensen, Kjetil N; Lange, Elisabeth H; Andreassen, Ole A; Melle, Ingrid; Agartz, Ingrid

    2015-05-01

    Apathy is an enduring and debilitating feature related to poor outcome in patients with first-episode psychosis (FEP). The biological underpinnings of apathy are unknown. We tested if FEP patients with persistent apathy (PA) differed from FEP patients without persistent apathy (NPA) in specific brain structure measures in the early phase of illness. A total of 70 Norwegian FEP patients were recruited within 1 year of first adequate treatment. They were defined as having PA (N=18) or NPA (N=52) based on Apathy Evaluation Scale score at baseline and 1 year later. MRI measures of cortical thickness and subcortical structure volumes were compared between the PA and NPA groups. The PA group had significantly thinner left orbitofrontal cortex and left anterior cingulate cortex. The results remained significant after controlling for depressive symptoms and antipsychotic medication. FEP patients with persistent apathy in the early phase of their illness show brain structural changes compared to FEP patients without persistent apathy. The changes are confined to regions associated with motivation, occur early in the disease course and appear selectively in PA patients when both groups are compared to healthy controls. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  9. The neuro-radiological anatomy of the normal and abnormal rat brain

    International Nuclear Information System (INIS)

    Schumacher, M.; Doller, P.; Voigt, K.

    1979-01-01

    In vivo and post mortem techniques for the radiological examination of normal brains have been developed, using 66 white adult rats. Aortic arch injections for survey angiograms (10 animals), selective catheterisation of the internal carotid artery (16 animals) and ventriculography by percutaneous needle puncture (20 animals) were performed in vivo; the animals survived and the examinations could be repeated. The techniques proved useful and accurate methods for the radiological demonstration of the topography and morphology of cerebral vessels and chambers; they also provided information on the function of the cerebral circulation and C.S.F. dynamics. The findings were checked and correlated by post mortem studies (20 animals) using contact radiography, micro-angiography and casts of the ventricles. As a result, extensive topographic and anatomic information concerning the cerebral vessels in the rat was obtained, including some microscopic-radiological findings. The combined use of these methods provided a basis for studying the growth of experimentally induced brain tumours and the effect of various types of treatment. (orig.) [de

  10. Temporal fractal analysis of the rs-BOLD signal identifies brain abnormalities in autism spectrum disorder.

    Science.gov (United States)

    Dona, Olga; Hall, Geoffrey B; Noseworthy, Michael D

    2017-01-01

    Brain connectivity in autism spectrum disorders (ASD) has proven difficult to characterize due to the heterogeneous nature of the spectrum. Connectivity in the brain occurs in a complex, multilevel and multi-temporal manner, driving the fluctuations observed in local oxygen demand. These fluctuations can be characterized as fractals, as they auto-correlate at different time scales. In this study, we propose a model-free complexity analysis based on the fractal dimension of the rs-BOLD signal, acquired with magnetic resonance imaging. The fractal dimension can be interpreted as measure of signal complexity and connectivity. Previous studies have suggested that reduction in signal complexity can be associated with disease. Therefore, we hypothesized that a detectable difference in rs-BOLD signal complexity could be observed between ASD patients and Controls. Anatomical and functional data from fifty-five subjects with ASD (12.7 ± 2.4 y/o) and 55 age-matched (14.1 ± 3.1 y/o) healthy controls were accessed through the NITRC database and the ABIDE project. Subjects were scanned using a 3T GE Signa MRI and a 32-channel RF-coil. Axial FSPGR-3D images were used to prescribe rs-BOLD (TE/TR = 30/2000ms) where 300 time points were acquired. Motion correction was performed on the functional data and anatomical and functional images were aligned and spatially warped to the N27 standard brain atlas. Fractal analysis, performed on a grey matter mask, was done by estimating the Hurst exponent in the frequency domain using a power spectral density approach and refining the estimation in the time domain with de-trended fluctuation analysis and signal summation conversion methods. Voxel-wise fractal dimension (FD) was calculated for every subject in the control group and in the ASD group to create ROI-based Z-scores for the ASD patients. Voxel-wise validation of FD normality across controls was confirmed, and non-Gaussian voxels were eliminated from subsequent analysis. To maintain

  11. Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke: The ACROSS-China Study (Abnormal Glucose Regulation in Patients With Acute Stroke Across China).

    Science.gov (United States)

    Jing, Jing; Pan, Yuesong; Zhao, Xingquan; Zheng, Huaguang; Jia, Qian; Mi, Donghua; Chen, Weiqi; Li, Hao; Liu, Liping; Wang, Chunxue; He, Yan; Wang, David; Wang, Yilong; Wang, Yongjun

    2017-04-01

    Insulin resistance was common in patients with stroke. This study investigated the association between insulin resistance and outcomes in nondiabetic patients with first-ever acute ischemic stroke. Patients with ischemic stroke without history of diabetes mellitus in the ACROSS-China registry (Abnormal Glucose Regulation in Patients With Acute Stroke Across China) were included. Insulin resistance was defined as a homeostatis model assessment-insulin resistance (HOMA-IR) index in the top quartile (Q4). HOMA-IR was calculated as fasting insulin (μU/mL)×fasting glucose (mmol/L)/22.5. Multivariable logistic regression or Cox regression was performed to estimate the association between HOMA-IR and 1-year prognosis (mortality, stroke recurrence, poor functional outcome [modified Rankin scale score 3-6], and dependence [modified Rankin scale score 3-5]). Among the 1245 patients with acute ischemic stroke enrolled in this study, the median HOMA-IR was 1.9 (interquartile range, 1.1-3.1). Patients with insulin resistance were associated with a higher mortality risk than those without (adjusted hazard ratio, 1.68; 95% confidence interval, 1.12-2.53; P =0.01), stroke recurrence (adjusted hazard ratio, 1.57, 95% confidence interval, 1.12-2.19; P =0.008), and poor outcome (adjusted odds ratio, 1.42; 95% confidence interval, 1.03-1.95; P =0.03) but not dependence after adjustment for potential confounders. Higher HOMA-IR quartile categories were associated with a higher risk of 1-year death, stroke recurrence, and poor outcome ( P for trend =0.005, 0.005, and 0.001, respectively). Insulin resistance was associated with an increased risk of death, stroke recurrence, and poor outcome but not dependence in nondiabetic patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

  12. Brain structural abnormalities in behavior therapy-resistant obsessive-compulsive disorder revealed by voxel-based morphometry

    Directory of Open Access Journals (Sweden)

    Hashimoto N

    2014-10-01

    Full Text Available Nobuhiko Hashimoto,1 Shutaro Nakaaki,2 Akiko Kawaguchi,1 Junko Sato,1 Harumasa Kasai,3 Takashi Nakamae,4 Jin Narumoto,4 Jun Miyata,5 Toshi A Furukawa,6,7 Masaru Mimura2 1Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 2Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 3Department of Central Radiology, Nagoya City University Hospital, Nagoya, Japan; 4Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 5Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 6Department of Health Promotion and Human Behavior, 7Department of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan Background: Although several functional imaging studies have demonstrated that behavior therapy (BT modifies the neural circuits involved in the pathogenesis of obsessive-compulsive disorder (OCD, the structural abnormalities underlying BT-resistant OCD remain unknown. Methods: In this study, we examined the existence of regional structural abnormalities in both the gray matter and the white matter of patients with OCD at baseline using voxel-based morphometry in responders (n=24 and nonresponders (n=15 to subsequent BT. Three-dimensional T1-weighted magnetic resonance imaging was performed before the completion of 12 weeks of BT. Results: Relative to the responders, the nonresponders exhibited significantly smaller gray matter volumes in the right ventromedial prefrontal cortex, the right orbitofrontal cortex, the right precentral gyrus, and the left anterior cingulate cortex. In addition, relative to the responders, the nonresponders exhibited significantly smaller white matter volumes in the left cingulate bundle and the left superior frontal white matter. Conclusion: These results suggest that the brain

  13. THE TIME COURSE OF ABNORMALITIES IN THE BRAIN SUBCORTICAL VISUAL CENTRE FOLLOWING EARLY IMPAIRMENT OF BINOCULAR EXPERIENCE

    Directory of Open Access Journals (Sweden)

    S. V. Alekseenko

    2016-01-01

    Full Text Available Background: Amblyopia related to congenital strabismus belongs to neurological disorders since it is caused by structural and functional remodeling of the visual parts of the brain without any baseline retinal pathology. Although a large number of animal studies on experimentally induced strabismus, as well as clinical cases have been published, the mechanisms and time course of the processes within the brain structures are not fully understood. Aim: To study the time course of abnormalities in the dorsal lateral geniculate nucleus (LGNd in animals with surgically induced convergent strabismus. LGNd is the structure through which the information from the retina goes to the visual cortex separately for each eye. Materials and methods: 14 strabismic and 17 intact kittens of four age groups were studied. Histochemical method was used to identify cytochrome oxidase which is a  mitochondrial respiratory chain enzyme whose activity correlates with neuronal functional activity. Optical density in eye-specific layers  A  and A1 was measured on the images of stained LGNd sections, with calculation of the contrast difference between them. Results: In strabismic kittens, there were changes in activity of A and A1 layers in the projection of the central part of visual field in LGNd of both hemispheres. At early stages of their formation, a relative decrease in activity was found in both hemispheres in the LGNd layers innervated through non-crossed pathways from both retinae. Thereafter, the time course of abnormalities in LGNd of both hemispheres was different. In the hemisphere ipsilateral to the squinting eye, the difference in layer activity was highest at the age from 3 to 5 months. However, in the opposite hemisphere the same difference indicating a decreased activity in the layer of the squinting eye were observed only at the age of 5 months. Conclusion: The process of amblyopia development during congenital convergent strabismus is

  14. Immune function and brain abnormalities in patients with systemic lupus erythematosus without overt neuropsychiatric manifestations.

    Science.gov (United States)

    Kozora, E; Filley, C M; Zhang, L; Brown, M S; Miller, D E; Arciniegas, D B; Pelzman, J L; West, S G

    2012-04-01

    This study examined the relationship between immune, cognitive and neuroimaging assessments in subjects with systemic lupus erythematosus (SLE) without histories of overt neuropsychiatric (NP) disorders. In total, 84 subjects with nonNPSLE and 37 healthy controls completed neuropsychological testing from the American College of Rheumatology SLE battery. Serum autoantibody and cytokine measures, volumetric magnetic resonance imaging, and magnetic resonance spectroscopy data were collected on a subset of subjects. NonNPSLE subjects had lower scores on measures of visual/complex attention, visuomotor speed and verbal memory compared with controls. No clinically significant differences between nonNPSLE patients and controls were found on serum measures of lupus anticoagulant, anticardiolipin antibodies, beta 2-glycoproteins, or pro-inflammatory cytokines (interleukin (IL)-1, IL-6, interferon alpha (IFN-alpha), and interferon gamma (IFN-gamma)). Higher scores on a global cognitive impairment index and a memory impairment index were correlated with lower IFN-alpha. Few associations between immune functions and neuroimaging parameters were found. Results indicated that nonNPSLE patients demonstrated cognitive impairment but not immune differences compared with controls. In these subjects, who were relatively young and with mild disease, no relationship between cognitive dysfunction, immune parameters, or previously documented neuroimaging abnormalities were noted. Immune measures acquired from cerebrospinal fluid instead of serum may yield stronger associations.

  15. Eye and brain abnormalities in congenital muscular dystrophies caused by fukutin-related protein gene (FKRP) mutations.

    Science.gov (United States)

    Kava, Maina; Chitayat, David; Blaser, Susan; Ray, Peter N; Vajsar, Jiri

    2013-11-01

    Mutations in the fukutin-related protein gene account for a broad spectrum of phenotypes ranging from severe congenital muscular dystrophies to a much milder limb-girdle muscular dystrophy 2I. The involvement of the eyes is variable, with most patients having normal eye examination. We describe eye and brain abnormalities in a 16 month-old-boy with Walker-Warburg syndrome phenotype resulting from a novel fukutin-related protein gene mutation in exon 4 and compare these with other reported patients with fukutin-related protein gene mutation. All patients with reported fukutin-related protein gene mutations who had eye involvement were included. Their clinical features, brain magnetic resonance imaging, and eye findings were compared with our patient. Patients with fukutin-related protein gene mutation tend to have no or mild eye involvement (generally strabismus), with very few cases reported of moderate to severe eye involvement. Our patient with a novel mutation c.558dupC(p.Ala187fs) represents one of the most severe phenotypes described in regard to eye involvement. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Brain mechanisms of abnormal temperature perception in cold allodynia induced by ciguatoxin.

    Science.gov (United States)

    Eisenblätter, Anneka; Lewis, Richard; Dörfler, Arnd; Forster, Clemens; Zimmermann, Katharina

    2017-01-01

    Cold allodynia occurs as a major symptom of neuropathic pain states. It remains poorly treated with current analgesics. Ciguatoxins (CTXs), ichthyosarcotoxins that cause ciguatera, produce a large peripheral sensitization to dynamic cold stimuli in Aδ-fibers by activating sodium channels without producing heat or mechanical allodynia. We used CTXs as a surrogate model of cold allodynia to dissect the framework of cold allodynia-activated central pain pathways. Reversible cold allodynia was induced in healthy male volunteers by shallow intracutaneous injection of low millimolar concentrations of CTX into the dorsal skin of the forefoot. Cold and warm stimuli were delivered to the treated and the control site using a Peltier-driven thermotest device. Functional magnetic resonance imaging (fMRI) scans were acquired with a 3T MRI scanner using a blood oxygen level-dependent (BOLD) protocol. The CTX-induced substantial peripheral sensitization to cooling stimuli in Aδ-fibers is particularly retrieved in BOLD changes due to dynamic temperature changes and less during constant cooling. Brain areas that responded during cold allodynia were almost always located bilaterally and appeared in the medial insula, medial cingulate cortex, secondary somatosensory cortex, frontal areas, and cerebellum. Whereas these areas also produced changes in BOLD signal during the dynamic warming stimulus on the control site, they remained silent during the warming stimuli on the injected site. We describe the defining feature of the cold allodynia pain percept in the human brain and illustrate why ciguatera sufferers often report a perceptual temperature reversal. ANN NEUROL 2017;81:104-116. © 2016 American Neurological Association.

  17. The SH2B1 obesity locus and abnormal glucose homeostasis: lack of evidence for association from a meta-analysis in individuals of European ancestry.

    Science.gov (United States)

    Prudente, S; Copetti, M; Morini, E; Mendonca, C; Andreozzi, F; Chandalia, M; Baratta, R; Pellegrini, F; Mercuri, L; Bailetti, D; Abate, N; Frittitta, L; Sesti, G; Florez, J C; Doria, A; Trischitta, V

    2013-11-01

    The development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D. Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association. The SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n = 47,117) and four other published studies (n = 39,448). Variability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR) = 0.96; 0.89-1.04) or in the meta-analysis (OR = 1.01; 0.98-1.05). Our data exclude a role for the SH2B1 obesity locus in the modulation of AGH. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    Science.gov (United States)

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  19. Loss of neuronal integrity: a cause of hypometabolism in patients with traumatic brain injury without MRI abnormality in the chronic stage

    International Nuclear Information System (INIS)

    Shiga, Tohru; Matsuyama, Tetsuaki; Kageyama, Hiroyuki; Kohno, Tomoya; Tamaki, Nagara; Ikoma, Katsunori; Isoyama, Hirotaka; Katoh, Chietsugu; Kuge, Yuji; Terae, Satoshi

    2006-01-01

    Traumatic brain injury (TBI) causes brain dysfunction in many patients. However, some patients have severe brain dysfunction but display no abnormalities on magnetic resonance imaging (MRI). There have been some reports of hypometabolism even in such patients. The purpose of this study was to investigate the relationship between metabolic abnormality and loss of neuronal integrity in TBI patients with some symptoms but without MRI abnormalities. The study population comprised ten patients with TBI and ten normal volunteers. All of the patients were examined at least 1 year after the injury. 15 O-labelled gas PET and [ 11 C]flumazenil (FMZ) positron emission tomography (PET) were carried out. The cerebral metabolic rate of oxygen (CMRO 2 ) and binding potential (BP) images of FMZ were calculated. Axial T2WI, T2*WI and FLAIR images were obtained. Coronal images were added in some cases. All of the patients had normal MRI findings, and all showed areas with abnormally low CMRO 2 . Low uptake on BP images was observed in six patients (60%). No lesions that showed low uptake on BP images were without low CMRO 2 . On the other hand, there were 14 lesions with low CMRO 2 but without BP abnormalities. These results indicate that there are metabolic abnormalities in TBI patients with some symptoms after brain injury but without abnormalities on MRI. Some of the hypometabolic lesions showed low BP, indicating a loss of neuronal integrity. Thus, FMZ PET may have potential to distinguish hypometabolism caused by neuronal loss from that caused by other factors. (orig.)

  20. Risk of vigabatrin-associated brain abnormalities on MRI in the treatment of infantile spasms is dose-dependent.

    Science.gov (United States)

    Hussain, Shaun A; Tsao, Jackie; Li, Menglu; Schwarz, Madeline D; Zhou, Raymond; Wu, Joyce Y; Salamon, Noriko; Sankar, Raman

    2017-04-01

    Although the link between vigabatrin (VGB) and retinotoxicity is well known, little attention has been focused on the risk of VGB-associated brain abnormalities on magnetic resonance imaging (MRI) (VABAM), namely reversible-and largely asymptomatic-signal changes in the thalami, basal ganglia, brainstem tegmentum, and cerebellar nuclei. Using a large infantile spasms cohort, we set out to identify predictors of these phenomena. Children with infantile spasms were retrospectively identified. Brain MRI reports were serially reviewed without knowledge of VGB exposure. Upon VABAM discovery, records were systematically reviewed to ascertain presence of symptoms attributable to VGB. Separately, progress notes were sequentially reviewed to identify and quantify VGB exposure. We identified 507 brain MRI studies among 257 patients with infantile spasms. VGB treatment was documented in 143 children, with detailed exposure data available for 104, of whom 45 had at least one MRI study during VGB treatment. Among the limited subset of asymptomatic children who underwent MRI (n = 40), 6 exhibited VABAM. Risk of asymptomatic VABAM was dose-dependent, as peak (but not cumulative) VGB dosage was strongly associated with asymptomatic VABAM (p = 0.0028). In an exploratory analysis, we encountered 4 children with symptomatic VABAM among 104 patients with detailed VGB exposure data. Risk of symptomatic VABAM was seemingly dose-independent, and potentially associated with concomitant hormonal therapy (i.e., prednisolone and adrenocorticotropic hormone [ACTH]) (p = 0.039). We have demonstrated dose-dependent risk of asymptomatic VABAM and uncovered a possible association between symptomatic VABAM and concomitant hormonal therapy. Caution should be exercised in the use of high VGB dosage (i.e., >175 mg/kg/day), and further study is warranted to confirm the potential impact of hormonal therapy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  1. Hierarchical clustering of Alzheimer and 'normal' brains using elemental concentrations and glucose metabolism determined by PIXE, INAA and PET

    International Nuclear Information System (INIS)

    Cutts, D.A.; Spyrou, N.M.

    2001-01-01

    Brain tissue samples, obtained from the Alzheimer Disease Brain Bank, Institute of Psychiatry, London, were taken from both left and right hemispheres of three regions of the cerebrum, namely the frontal, parietal and occipital lobes for both Alzheimer and 'normal' subjects. Trace element concentrations in the frontal lobe were determined for twenty six Alzheimer (15 male, 11 female) and twenty six 'normal' (8 male, 18 female) brain tissue samples. In the parietal lobe ten Alzheimer (2 male, 8 female) and ten 'normal' (8 male, 2 female) samples were taken along with ten Alzheimer (4 male, 6 female) and ten 'normal' (6 male, 4 female) from the occipital lobe. For the frontal lobe trace element concentrations were determined using proton induced X-ray emission (PIXE) analysis while in parietal and occipital regions instrumental neutron activation analysis (INAA) was used. Additionally eighteen Alzheimer (9 male, 9 female) and eighteen age matched 'normal' (8 male, 10 female) living subjects were examined using positron emission tomography (PET) in order to determine regional cerebral metabolic rates of glucose (rCMRGlu). The rCMRGlu of 36 regions of the brain was investigated including frontal, occipital and parietal lobes as in the trace element study. Hierarchical cluster analysis was applied to the trace element and glucose metabolism data to discover which variables in the resulting dendrograms displayed the most significant separation between Alzheimer and 'normal' subjects. (author)

  2. Schizophrenia and Category-Selectivity in the Brain: Normal for Faces but Abnormal for Houses

    Directory of Open Access Journals (Sweden)

    Lisa Kronbichler

    2018-02-01

    Full Text Available Face processing is regularly found to be impaired in schizophrenia (SZ, thus suggesting that social malfunctioning might be caused by dysfunctional face processing. Most studies focused on emotional face processes, whereas non-emotional face processing received less attention. While current reports on abnormal face processing in SZ are mixed, examinations of non-emotional face processing compared to adequate control stimuli may clarify whether SZ is characterized by a face-processing deficit. Patients with SZ (n = 28 and healthy controls (n = 30 engaged in an fMRI scan where images of non-emotional faces and houses were presented. A simple inverted-picture detection task warranted the participants’ attention. Region of interest (ROI analyses were conducted on face-sensitive regions including the fusiform face area, the occipital face area, and the superior temporal sulcus. Scene-sensitivity was assessed in the parahippocampal place area (PPA and served as control condition. Patients did not show aberrant face-related neural processes in face-sensitive regions. This finding was also evident when analyses were done on individually defined ROIs or on in-house-localizer ROIs. Patients revealed a decreased specificity toward house stimuli as reflected in decreased neural response toward houses in the PPA. Again, this result was supported by supplementary analyses. Neural activation toward neutral faces was not found to be impaired in SZ, therefore speaking against an overall face-processing deficit. Aberrant activation in scene-sensitive PPA is also found in assessments of memory processes in SZ. It is up to future studies to show how impairments in PPA relate to functional outcome in SZ.

  3. Profiling brain function: spatiotemporal characterization of normal and abnormal visual activation.

    Science.gov (United States)

    Versteeg, Vanessa L; Marchand, Yannick; Mazerolle, Erin L; D'Arcy, Ryan C N

    2010-06-30

    In clinical neuroscience, the utility of evoked and event-related potentials (EPs and ERPs) resides in the temporal information they provide. However, it is largely unknown whether valuable diagnostic information resides within the corresponding spatial patterns. To determine this, the first step involves testing whether "normal" versus "abnormal" EPs/ERPs can be differentiated based on spatial patterns. In the current study, we present a method that characterizes similarities across individual source maps, called the profile algorithm. The profile algorithm was evaluated in terms of its ability to detect spatial activation differences in myopic individuals with corrected and uncorrected vision. This experiment represents a critical test of the method before applying it to the assessment of perceptual/cognitive functions. Visual-evoked potentials (VEPs) were recorded from healthy subjects using checkerboard stimulation. The N75 and P100 were examined in individuals with corrected (20/20) and uncorrected vision (20/40 or worse). N75 and P100 amplitudes and latencies were modulated by vision condition. The profile algorithm differentiated successfully between corrected and uncorrected vision. Its discriminatory power outperformed a more traditional method based on ERP peak amplitude. Subsequent correlations revealed significant relationships between visual impairment and both the components and the spatial activation. Overall, the findings suggested that VEP spatial patterns were sensitive to manipulations of visual acuity. The findings demonstrate that EP/ERP spatial activation can be evaluated at the individual level and compared against normative data. Ultimately, the method may provide a valuable tool for assessing individual spatial activation changes in perceptual/cognitive functions. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

  4. Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®.

    Science.gov (United States)

    Shoemaker, Ritchie C; House, Dennis; Ryan, James C

    2014-01-01

    Executive cognitive and neurologic abnormalities are commonly seen in patients with a chronic inflammatory response syndrome (CIRS) acquired following exposure to the interior environment of water-damaged buildings (WDB), but a clear delineation of the physiologic or structural basis for these abnormalities has not been defined. Symptoms of affected patients routinely include headache, difficulty with recent memory, concentration, word finding, numbness, tingling, metallic taste and vertigo. Additionally, persistent proteomic abnormalities in inflammatory parameters that can alter permeability of the blood-brain barrier, such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB compared to controls, suggesting a consequent inflammatory injury to the central nervous system. Findings of gliotic areas in MRI scans in over 45% of CIRS-WDB cases compared to 5% of controls, as well as elevated lactate and depressed ratios of glutamate to glutamine, are regularly seen in MR spectroscopy of cases. This study used the volumetric software program NeuroQuant® (NQ) to determine specific brain structure volumes in consecutive patients (N=17) seen in a medical clinic specializing in inflammatory illness. Each of these patients presented for evaluation of an illness thought to be associated with exposure to WDB, and received an MRI that was evaluated by NQ. When compared to those of a medical control group (N=18), statistically significant differences in brain structure proportions were seen for patients in both hemispheres of two of the eleven brain regions analyzed; atrophy of the caudate nucleus and enlargement of the pallidum. In addition, the left amygdala and right forebrain were also enlarged. These volumetric abnormalities, in conjunction with concurrent abnormalities in inflammatory markers, suggest a model for structural brain injury in "mold illness" based on increased permeability of the blood-brain barrier due to chronic, systemic inflammation

  5. Cerebral glucose metabolism in long-term survivors of childhood primary brain tumors treated with surgery and radiotherapy

    DEFF Research Database (Denmark)

    Andersen, Preben B.; Krabbe, Katja; Leffers, Anne M.

    2003-01-01

    Delayed structural cerebral sequelae has been reported following cranial radiation therapy (CRT) to children with primary brain tumors, but little is known about potential functional changes. Twenty-four patients were included, diagnosed and treated at a median age of 11 years, and examined after...... that there is a general reduction in rCMRglc in long-term recurrence free survivors of childhood primary brain tumors treated with CRT in high doses (44-56 Gy)...... evaluable and regional cerebral metabolic rate for glucose (rCMRglc) was estimated in nontumoral brain regions in 12 patients treated with surgery alone and 9 patients treated with both surgery and CRT. Furthermore 10 normal controls matched for age at examination were included. Patients treated with both...

  6. Structural brain abnormalities in postural tachycardia syndrome: A VBM-DARTEL study

    Directory of Open Access Journals (Sweden)

    Satoshi eUmeda

    2015-03-01

    Full Text Available Postural tachycardia syndrome (PoTS, a form of dysautonomia, is characterized by orthostatic intolerance, and is frequently accompanied by a range of symptoms including palpitations, lightheadedness, clouding of thought, blurred vision, fatigue, anxiety and depression. Although the estimated prevalence of PoTS is approximately 5-10 times ascommon as the better-known condition orthostatic hypotension, the neural substrates of the syndrome are poorly characterized. In the present study, we used magnetic resonance imaging (MRI with voxel-based morphometry (VBM applying the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL procedure to examine variation in regional brain structure associated with PoTS. We recruited eleven patients with established PoTS and twenty-three age-matched normal controls. Group comparison of grey matter volume revealed diminished grey matter volume within the left anterior insula, right middle frontal gyrus and right cingulate gyrus in the PoTS group. We also observed lower white matter volume beneath the precentral gyrus and paracentral lobule, right pre- and post-central gyrus, paracentral lobule and superior frontal gyrus in PoTS patients. Subsequent ROI analyses revealed significant negative correlations between left insula volume and trait anxiety and depression scores. Together, these findings of structural differences, particularly within insular and cingulate components of the salience network, suggest a link between dysregulated physiological reactions arising from compromised central autonomic control (and interoceptive representation and increased vulnerability to psychiatric symptoms in PoTS patients.

  7. Abnormal functional lateralization and activity of language brain areas in typical specific language impairment (developmental dysphasia)

    Science.gov (United States)

    De Guibert, Clément; Maumet, Camille; Jannin, Pierre; Ferré, Jean-Christophe; Tréguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting structural language (n=21), to a matched group of typically-developing children using a panel of four language tasks neither requiring reading nor metalinguistic skills, including two auditory lexico-semantic tasks (category fluency and responsive naming) and two visual phonological tasks based on picture naming. Data processing involved normalizing the data with respect to a matched pairs pediatric template, groups and between-groups analysis, and laterality indexes assessment within regions of interest using single and combined task analysis. Children with specific language impairment exhibited a significant lack of left lateralization in all core language regions (inferior frontal gyrus-opercularis, inferior frontal gyrus-triangularis, supramarginal gyrus, superior temporal gyrus), across single or combined task analysis, but no difference of lateralization for the rest of the brain. Between-group comparisons revealed a left hypoactivation of Wernicke’s area at the posterior superior temporal/supramarginal junction during the responsive naming task, and a right hyperactivation encompassing the anterior insula with adjacent inferior frontal gyrus and the head of the caudate nucleus during the first phonological task. This study thus provides evidence that this specific subtype of specific language impairment is associated with atypical lateralization and functioning of core language areas. PMID:21719430

  8. Continued glucose output after re-feeding contributes to glucose intolerance in hyperthyroidism.

    OpenAIRE

    Holness, M J; Sugden, M C

    1987-01-01

    The effects of hyperthyroidism to elicit glucose intolerance after glucose administration were decreased under conditions where hepatic glucose output was suppressed. It is concluded that continued hepatic glucose output contributes to abnormal glucose tolerance in hyperthyroidism.

  9. Analysis of abnormal findings observed on brain MRI T2 weighted image in a system for the detection of asymptomatic brain disease in 1,200 cases

    International Nuclear Information System (INIS)

    Horiguchi, Takashi; Yoshida, Kazunari; Sato, Syuzo; Kawase, Takeshi; Toya, Shigeo; Mizukami, Masahiro

    1998-01-01

    In this study we described the significance of asymptomatic cerebral infarction (ACI) and periventricular hyperintensity (PVH) observed on brain MRI in a system for detection of asymptomatic brain disease with 1,200 cases. The risk factors (RF), population in each age bracket of ACI and PVH, among groups with hypertension (HTG) and without RF (no-RFG), were investigated. The RF of ACI were hypertension (HT), diabetes mellitus (DM), and aging. Without DM, those are common RF of PVH. The population of PVH and ACI with PVH increased with aging in no-RFG. On the other hand, only the population of ACI with PVH increased with aging in HTG. The rate of these abnormal findings in HTG was significantly higher than that in no-RFG. In addition, HT accelerated the occurrence of these findings by 10-20 years. When patients were over 60 years old, ACI increased rapidly. Accordingly, we concluded that PVH and ACI had a common background. Long term follow up concerning the incidence of ACI in the group with only PVH was necessary. It was desirable that treatment for RF should be effected before the age of sixty. (author)

  10. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

    Science.gov (United States)

    Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

    2012-10-01

    It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. Copyright © 2012 John Wiley & Sons, Ltd.

  11. Is Insulin Action in the Brain Relevant in Regulating Blood Glucose in Humans?

    Science.gov (United States)

    Dash, Satya; Xiao, Changting; Morgantini, Cecilia; Koulajian, Khajag; Lewis, Gary F

    2015-07-01

    In addition to its direct action on the liver to lower hepatic glucose production, insulin action in the central nervous system (CNS) also lowers hepatic glucose production in rodents after 4 hours. Although CNS insulin action (CNSIA) modulates hepatic glycogen synthesis in dogs, it has no net effect on hepatic glucose output over a 4-hour period. The role of CNSIA in regulating plasma glucose has recently been examined in humans and is the focus of this review. Intransal insulin (INI) administration increases CNS insulin concentration. Hence, INI can address whether CNSIA regulates plasma glucose concentration in humans. We and three other groups have sought to answer this question, with differing conclusions. Here we will review the critical aspects of each study, including its design, which may explain these discordant conclusions. The early glucose-lowering effect of INI is likely due to spillover of insulin into the systemic circulation. In the presence of simultaneous portal and CNS hyperinsulinemia, portal insulin action is dominant. INI administration does lower plasma glucose independent of peripheral insulin concentration (between ∼3 and 6 h after administration), suggesting that CNSIA may play a role in glucose homeostasis in the late postprandial period when its action is likely greatest and portal insulin concentration is at baseline. The potential physiological role and purpose of this pathway are discussed in this review. Because the effects of INI are attenuated in patients with type 2 diabetes and obesity, this is unlikely to be of therapeutic utility.

  12. Clinical manifestations that predict abnormal brain computed tomography (CT in children with minor head injury

    Directory of Open Access Journals (Sweden)

    Nesrin Alharthy

    2015-01-01

    Full Text Available Background: Computed tomography (CT used in pediatric pediatrics brain injury (TBI to ascertain neurological manifestations. Nevertheless, this practice is associated with adverse effects. Reports in the literature suggest incidents of morbidity and mortality in children due to exposure to radiation. Hence, it is found imperative to search for a reliable alternative. Objectives: The aim of this study is to find a reliable clinical alternative to detect an intracranial injury without resorting to the CT. Materials and Methods: Retrospective cross-sectional study was undertaken in patients (1-14 years with blunt head injury and having a Glasgow Coma Scale (GCS of 13-15 who had CT performed on them. Using statistical analysis, the correlation between clinical examination and positive CT manifestation is analyzed for different age-groups and various mechanisms of injury. Results: No statistically significant association between parameteres such as Loss of Consciousness, ′fall′ as mechanism of injury, motor vehicle accidents (MVA, more than two discrete episodes of vomiting and the CT finding of intracranial injury could be noted. Analyzed data have led to believe that GCS of 13 at presentation is the only important clinical predictor of intracranial injury. Conclusion: Retrospective data, small sample size and limited number of factors for assessing clinical manifestation might present constraints on the predictive rule that was derived from this review. Such limitations notwithstanding, the decision to determine which patients should undergo neuroimaging is encouraged to be based on clinical judgments. Further analysis with higher sample sizes may be required to authenticate and validate findings.

  13. Autism Spectrum Disorder as Early Neurodevelopmental Disorder: Evidence from the Brain Imaging Abnormalities in 2-3 Years Old Toddlers

    Science.gov (United States)

    Xiao, Zhou; Qiu, Ting; Ke, Xiaoyan; Xiao, Xiang; Xiao, Ting; Liang, Fengjing; Zou, Bing; Huang, Haiqing; Fang, Hui; Chu, Kangkang; Zhang, Jiuping; Liu, Yijun

    2014-01-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships…

  14. Pattern of mri brain abnormalities in rheumatic patients with neurological involvement: a tertiary care teaching hospital experience

    International Nuclear Information System (INIS)

    Parvez, K.; Arfaj, A.; Naseeb, F.; Daif, A.K.

    2015-01-01

    Objective: To explore the pattern of abnormalities seen on MRI in rheumatic patients with neurological manifestations and to interpret the findings in relation to clinical picture. Study Design: Descriptive study. Place and Duration of Study: Rheumatology unit, King Khalid University Hospital, Riyadh, Saudi Arabia from January 2013 to February 2014. Patients and Methods: We prospectively included rheumatic patients with neurological symptoms and signs. The clinical data were correlated with MRI findings by a team comprising of a rheumatologist, neurologist and neuro-radiologist. Data was analyzed using simple statistical analysis. Results: Fifty patients were recruited with a mean age of 36.4 ± 10.76 years (range 17-62). Among SLE patients with seizures, focal deficit and headache white matter hyperintensities were found in 9 (64.28%), 4 (50%), 4 (80%) patients respectively. Out of seven SLE patients with global dysfunction, 3 (42.85%) had brain atrophy and 2 (28.57%) normal MRI. In Behcet disease with focal deficit, 3 (75%) patients had white matter hyperintensities and 1 (25%) had brainstem involvement. In Behcet disease with headache, 2 (50%) had normal MRI, 1 (25%) brainstem hyper-intensities and 1 (25%) had subacute infarct. Two (66%) of three Primary APS patients had white matter hyperintensities while third (33%) had old infarct. Both patients of polyarteritisnodosa, had white matter hyperintensities. Out of two Wegener granulomatosis one had white matter hyperintensities and other had ischemic changes in optic nerves. The only one scleroderma patient had white matter hyperintensities. Conclusion: We found that white matter hyperintensities was the most common MRI abnormality in our study group which in most of the cases had poor clinical correlation. No distinct pattern of CNS involvement on MRI was observed in various rheumatic disorders. (author)

  15. Gender differences of brain glucose metabolic networks revealed by FDG-PET: evidence from a large cohort of 400 young adults.

    Science.gov (United States)

    Hu, Yuxiao; Xu, Qiang; Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

    2013-01-01

    Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age ± SD: 40.9 ± 3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.

  16. Acute but not chronic activation of brain glucagon-like peptide-1 receptors enhances glucose-stimulated insulin secretion in mice.

    Science.gov (United States)

    Tudurí, E; Beiroa, D; Porteiro, B; López, M; Diéguez, C; Nogueiras, R

    2015-08-01

    To investigate the role of brain glucagon-like peptide-1 (GLP-1) in pancreatic β-cell function. To determine the role of brain GLP-1 receptor (GLP-1R) on β-cell function, we administered intracerebroventricular (i.c.v.) infusions of GLP-1 or the specific GLP-1 antagonist exendin-9 (Ex-9), in both an acute and a chronic setting. We observed that acute i.c.v. GLP-1 infusion potentiates glucose-stimulated insulin secretion (GSIS) and improves glucose tolerance, whereas central GLP-1R blockade with Ex-9 impaired glucose excursion after a glucose load. Sustained activation of central nervous system GLP-1R, however, did not produce any effect on either GSIS or glucose tolerance. Similarly, ex vivo GSIS performed in islets from mice chronically infused with i.c.v. GLP-1 resulted in no differences compared with controls. In addition, in mice fed a high-fat diet we observed that acute i.c.v. GLP-1 infusion improved glucose tolerance without changes in GSIS, while chronic GLP-1R activation had no effect on glucose homeostasis. Our results indicate that, under non-clamped conditions, brain GLP-1 plays a functional neuroendocrine role in the acute regulation of glucose homeostasis in both lean and obese rodents. © 2015 John Wiley & Sons Ltd.

  17. Effects of normobaric versus hyperbaric oxygen on cell injury induced by oxygen and glucose deprivation in acute brain slices

    Directory of Open Access Journals (Sweden)

    Laurent Chazalviel

    2016-01-01

    Full Text Available Normobaric oxygen (NBO and hyperbaric oxygen (HBO are emerging as a possible co-treatment of acute ischemic stroke. Both have been shown to reduce infarct volume, to improve neurologic outcome, to promote endogenous tissue plasminogen activator-induced thrombolysis and cerebral blood flow, and to improve tissue oxygenation through oxygen diffusion in the ischemic areas, thereby questioning the interest of HBO compared to NBO. In the present study, in order to investigate and compare the oxygen diffusion effects of NBO and HBO on acute ischemic stroke independently of their effects at the vascular level, we used acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of brain ischemia that allows investigating the acute effects of NBO (partial pressure of oxygen (pO 2 = 1 atmospheres absolute (ATA = 0.1 MPa and HBO (pO 2 = 2.5 ATA = 0.25 MPa through tissue oxygenation on ischemia-induced cell injury as measured by the release of lactate dehydrogenase. We found that HBO, but not NBO, reduced oxygen and glucose deprivation-induced cell injury, indicating that passive tissue oxygenation (i.e. without vascular support of the brain parenchyma requires oxygen partial pressure higher than 1 ATA.

  18. PCP-induced alterations in cerebral glucose utilization in rat brain: blockade by metaphit, a PCP-receptor-acylating agent

    International Nuclear Information System (INIS)

    Tamminga, C.A.; Tanimoto, K.; Kuo, S.; Chase, T.N.; Contreras, P.C.; Rice, K.C.; Jackson, A.E.; O'Donohue, T.L.

    1987-01-01

    The effects of phencyclidine (PCP) on regional cerebral glucose utilization was determined by using quantitative autoradiography with [ 14 C]-2-deoxyglucose. PCP increased brain metabolism in selected areas of cortex, particularly limbic, and in the basal ganglia and thalamus, whereas the drug decreased metabolism in areas related to audition. These results are consistent with the known physiology of central PCP neurons and may help to suggest brain areas involved in PCP-mediated actions. Moreover, based on the behavioral similarities between PCP psychosis and an acute schizophrenic episode, these data may be relevant to the understanding of schizophrenia. The PCP-receptor-acylating agent, metaphit, blocked most of these PCP actions. In addition, metaphit by itself was found to diminish glucose utilization rather uniformly throughout brain. These results indicate an antagonist effect of metaphit on the PCP system and suggest a widespread action of metaphit, putatively at a PCP-related site, possibly in connection with the N-methyl-D-aspartate (NMDA) receptor

  19. Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain

    DEFF Research Database (Denmark)

    Jensen, Vivi F. H.; Molck, Anne-Marie; Chapman, Melissa

    2017-01-01

    The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels...... of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different...... substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30–50% (4–6 mM versus 7–9 mM in controls). The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain...

  20. Neuropsychological deficits and morphological MRI brain scan abnormalities in apparently health non-encephalopathic patients with cirrhosis

    International Nuclear Information System (INIS)

    Moore, J.W.; De Lacey, G.; Dunk, A.A.; Sinclair, T.S.; Mowat, M.A.G.; Brunt, P.W.; Deans, H.; Crawford, J.R.; Besson, J.A.O.

    1989-01-01

    By means of psychometric testing, we have determined the frequency of latent hepatic encephalopathy in a group of 19 cirrhotics with no clinical evidence of encephalopathy. Magnetic resonance imaging (MRI) of the brain was performed in order to determine whether morphological cerebral abnormalities were associated with latent encephalopathy. Nineteen age and educationally matched patient with normal liver function acted as controls. Significant differences (P < 0.05) between cirrhotics and controls were found in tests of short-term visual memory and speed of reaction to light (cirrhotics 326 ] 132 ms vs. controls 225 ] 36 ms), sound (cirrhotics 361 ] 152 ms vs. controls 236 ] 52 ms) and choice (cirrhotics 651 ] 190 ms vs. controls 406 ] 101 ms) stimuli (all values mean ] S.D.). Reitan trail test performance, however, was similar in both groups. ( Trail A: cirrhotics 43 ] 19 s vs. controls 35 ] 13 s; Trail B: cirrhotics 105 ] 66 s vs. controls 93 ] 36 s.) In patients with cirrhosis, MRI revealed statistically significant increases in the maximum fissure width of right frontal sulci, light and left parietal sulci, inter-hemispheric fissure width and in bicaudafe index. These changes, indicating cerebral atrophy, were largely confined to alcoholics. There was poor correlation between measurements of cerebral morphology and neuropsychological performance, only 10% of associations achieving statistical significance. (author). 2 refs.; 3 figs.; 5 tabs

  1. Brain regions involved in voluntary movements as revealed by radioisotopic mapping of CBF or CMR-glucose changes

    DEFF Research Database (Denmark)

    Lassen, N A; Ingvar, D H

    1990-01-01

    Mapping of cortical and subcortical grey matter active during voluntary movements by means of measurements of local increases of CBF or CMR-Glucose is reviewed. Most of the studies concern observations in man during hand movements using the intracarotid Xenon-133 injection technique, an approach...... that only allows to image the cortex of the hemisphere on one side (the injected side) of the brain. The results show that simple static or repetitive movements mainly activate the contralateral primary hand area (MI and SI); complex preprogrammed or spontaneous purposeful movements the supplementary motor...

  2. Quantitative autoradiography of 14C-D-glucose metabolism of normal and traumatized rat brain using micro-absorption photometry

    International Nuclear Information System (INIS)

    Bonorden, S.

    1980-01-01

    It could be shown using 14 C-glucose as energy-providing substrate for brain tissue metabolism that for bolus type application a retarded and even channelling of the substrate into the metabolic process takes place. The presence of tracer in the tissue was established using autoradiography. A linear correlation between the amount of tissue-incorporated 14 C section thickness and exposure time could be established by means of densitometric measurement of brain sections of various thicknesses, by applying various 14 C-activities and by different exposure times. From these correlations direct conclusions may be made regarding the specific activity of the tissue provided that exposure time and section thickness of the sample are known. Comparative studies between cortex and narrow and between traumatized and non-traumatized brain tissue show that the rate of metabolism in brain cortex is markedly higher than in the marrow and that 14 C-incorporation is higher in traumatized tissue than in non-traumatized tissue. Whilst the difference in rate of metabolism between brain cortex and marrow can be clearly related to the differing cell count/unit surface area for cortex and marrow, the different energy conversion rates for functionally damaged and normal brain tissue is a specific characteristic of injury. Apart from the fact that an increased 14 C-deposition is in no way indicative of an increased metabolic activity, the possibility of quantifying 14 C-tissue content provides a basis for estimating therapeutic effects e.g. in the treatment of trauma-caused brain edema. (orig.) [de

  3. A comparison between the impact of two types of dietary protein on brain glucose concentrations and oxidative stress in high fructose-induced metabolic syndrome rats.

    Science.gov (United States)

    Madani, Zohra; Malaisse, Willy J; Ait-Yahia, Dalila

    2015-09-01

    The present study explored the potential of fish proteins to counteract high glucose levels and oxidative stress induced by fructose in the brain. A total of 24 male Wistar rats consumed sardine protein or casein with or without high fructose (64%). After 2 months, brain tissue was used for analyses. The fructose rats exhibited an increase in body mass index (BMI), body weight, absolute and relative brain weights and brain glucose; however, there was a decrease in food and water intake. Fructose disrupts membrane homeostasis, as evidenced by an increase in the brain hydroperoxides and a decrease in catalase (CAT) and glutathione peroxidase (GSH-Px) compared to the control. The exposure to the sardine protein reduced BMI, food intake, glucose and hydroperoxides, and increased CAT and GSH-Px in the brain. In conclusion, the metabolic dysfunctions associated with the fructose treatment were ameliorated by the presence of sardine protein in the diet by decreasing BMI, brain glucose and lipid peroxidation, and increasing CAT and GSH-Px activities.

  4. Resting-State EEG Oscillatory Dynamics in Fragile X Syndrome: Abnormal Functional Connectivity and Brain Network Organization

    NARCIS (Netherlands)

    van der Molen, M.J.W.; Stam, C.J.; van der Molen, M.W.

    2014-01-01

    Disruptions in functional connectivity and dysfunctional brain networks are considered to be a neurological hallmark of neurodevelopmental disorders. Despite the vast literature on functional brain connectivity in typical brain development, surprisingly few attempts have been made to characterize

  5. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    International Nuclear Information System (INIS)

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-01-01

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET- 18 FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

  6. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

  7. Oxygen-Glucose Deprivation Induces G2/M Cell Cycle Arrest in Brain Pericytes Associated with ERK Inactivation.

    Science.gov (United States)

    Wei, Wenjie; Yu, Zhiyuan; Xie, Minjie; Wang, Wei; Luo, Xiang

    2017-01-01

    Growing evidence has revealed that brain pericytes are multifunctional and contribute to the pathogenesis of a number of neurological disorders. However, the role of pericytes in cerebral ischemia, and especially the pathophysiological alterations in pericytes, remains unclear. In the present study, our aim was to determine whether the proliferation of pericytes is affected by cerebral ischemia and, if so, to identify the underlying mechanism(s). Cultured brain pericytes subjected to oxygen-glucose deprivation (OGD) were used as our model of cerebral ischemia; the protein expression levels of cyclin D1, cyclin E, cdk4, and cyclin B1 were determined by Western blot analysis, and cell cycle analysis was assessed by flow cytometry. The OGD treatment reduced the brain pericyte proliferation by causing G2/M phase arrest and downregulating the protein levels of cyclin D1, cyclin E, cdk4, and cyclin B1. Further studies demonstrated a simultaneous decrease in the activity of extracellular regulated protein kinases (ERK), suggesting a critical role of the ERK signaling cascade in the inhibition of OGD-induced pericyte proliferation. We suggest that OGD inhibition of the proliferation of brain pericytes is associated with the inactivation of the ERK signaling pathway, which arrests them in the G2/M phase.

  8. Effect of hyperbaric oxygen on glucose utilization in a freeze-traumatized rat brain

    International Nuclear Information System (INIS)

    Contreras, F.L.; Kadekaro, M.; Eisenberg, H.M.

    1988-01-01

    Local cerebral glucose utilization was measured with the autoradiographic 2-deoxyglucose technique in rats injured by a focal parietal cortical freeze lesion then treated with hyperbaric oxygen (HBO). The cold lesion depressed glucose utilization in the contralateral as well as in the ipsilateral hemisphere. The largest decreases were observed in ipsilateral cortical areas. Treatment of lesioned animals with HBO at 2 atm for 90 minutes on each of 4 consecutive days tended to increase the overall cerebral glucose utilization measured 5 days after injury when compared to animals exposed to normobaric air. This improvement reached statistical significance in five of the 21 structures studied: the auditory cortex, medial geniculate body, superior olivary nucleus, and lateral geniculate body ipsilateral to the lesion, and the mammillary body. The data indicate that changes in lesioned rats exposed to HBO are not restricted to the period of time that the animals are in the hyperbaric chamber but are persistent

  9. Brain Imaging and Blood Biomarker Abnormalities in Children With Autosomal Dominant Alzheimer Disease: A Cross-Sectional Study.

    Science.gov (United States)

    Quiroz, Yakeel T; Schultz, Aaron P; Chen, Kewei; Protas, Hillary D; Brickhouse, Michael; Fleisher, Adam S; Langbaum, Jessica B; Thiyyagura, Pradeep; Fagan, Anne M; Shah, Aarti R; Muniz, Martha; Arboleda-Velasquez, Joseph F; Munoz, Claudia; Garcia, Gloria; Acosta-Baena, Natalia; Giraldo, Margarita; Tirado, Victoria; Ramírez, Dora L; Tariot, Pierre N; Dickerson, Bradford C; Sperling, Reisa A; Lopera, Francisco; Reiman, Eric M

    2015-08-01

    cingulate cortex with medial temporal lobe regions (mean [SD] parameter estimates were 0.038 [0.070] for noncarriers and 0.190 [0.057] for carriers), as well as greater gray matter volumes in temporal regions (eg, left parahippocampus; P < . 049, corrected for multiple comparisons). Children at genetic risk for ADAD have functional and structural brain changes and abnormal levels of plasma Aβ1-42. The extent to which the underlying brain changes are either neurodegenerative or developmental remains to be determined. This study provides additional information about the earliest known biomarker changes associated with ADAD.

  10. Abnormal functional connectivity of brain network hubs associated with symptom severity in treatment-naive patients with obsessive-compulsive disorder: A resting-state functional MRI study.

    Science.gov (United States)

    Tian, Lin; Meng, Chun; Jiang, Ying; Tang, Qunfeng; Wang, Shuai; Xie, Xiyao; Fu, Xiangshuai; Jin, Chunhui; Zhang, Fuquan; Wang, Jidong

    2016-04-03

    Abnormal brain networks have been observed in patients with obsessive-compulsive disorder (OCD). However, detailed network hub and connectivity changes remained unclear in treatment-naive patients with OCD. Here, we sought to determine whether patients show hub-related connectivity changes in their whole-brain functional networks. We used resting-state functional magnetic resonance imaging data and voxel-based graph-theoretic analysis to investigate functional connectivity strength and hubs of whole-brain networks in 29 treatment-naive patients with OCD and 29 age- and gender-matched healthy controls. Correlation analysis was applied for potential associations with OCD symptom severity. OCD selectively targeted brain regions of higher functional connectivity strength than the average including brain network hubs, mainly distributed in the cortico-striato-thalamo-cortical (CSTC) circuits and additionally parietal, occipital, temporal and cerebellar regions. Moreover, affected functional connectivity strength in the cerebellum, the medial orbitofrontal cortex and superior occipital cortex was significantly associated with global OCD symptom severity. Our results provide the evidence about OCD-related brain network hub changes, not only in the CSTC circuits but more distributed in whole brain networks. Data suggest that whole brain network hub analysis is useful for understanding the pathophysiology of OCD. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. At the centennial of Michaelis and Menten, competing Michaelis-Menten steps explain effect of GLP-1 on blood-brain transfer and metabolism of glucose

    DEFF Research Database (Denmark)

    Jensen, Michael Gejl; Rungby, Jørgen; Brock, Birgitte

    2014-01-01

    and Maud Menten described the steady-state enzyme kinetics that still apply to the multiple receptors, transporters and enzymes that define the biochemical reactions of the brain, including the glucose-dependent impact of GLP-1 on blood-brain glucose transfer and metabolism. This MiniReview examines......Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic incretin hormone with pancreatic and extrapancreatic effects. Studies reveal significant effects in regions of brain tissue that regulate appetite and satiety. The effects cause that mimetics of GLP-1 serves as treatment of type 2 diabetes...... the potential of GLP-1 as a molecule of interest to the understanding of brain energy metabolism and notes the impact on brain metabolism related to appetite and satiety regulation, stroke and neurodegenerative disorders, among others. These effects can be understood only by reference to the original...

  12. High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Charles W. Wilkinson

    2012-02-01

    Full Text Available Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least one year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP to be unrelated to injury severity. Growth hormone deficiency (GHD and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI, an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least one year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and

  13. Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer's mouse brain: implication for bioenergetic intervention.

    Science.gov (United States)

    Ding, Fan; Yao, Jia; Rettberg, Jamaica R; Chen, Shuhua; Brinton, Roberta Diaz

    2013-01-01

    We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3-15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6-9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

  14. Influence of Glucose Deprivation on Membrane Potentials of Plasma Membranes, Mitochondria and Synaptic Vesicles in Rat Brain Synaptosomes.

    Science.gov (United States)

    Hrynevich, Sviatlana V; Pekun, Tatyana G; Waseem, Tatyana V; Fedorovich, Sergei V

    2015-06-01

    Hypoglycemia can cause neuronal cell death similar to that of glutamate-induced cell death. In the present paper, we investigated the effect of glucose removal from incubation medium on changes of mitochondrial and plasma membrane potentials in rat brain synaptosomes using the fluorescent dyes DiSC3(5) and JC-1. We also monitored pH gradients in synaptic vesicles and their recycling by the fluorescent dye acridine orange. Glucose deprivation was found to cause an inhibition of K(+)-induced Ca(2+)-dependent exocytosis and a shift of mitochondrial and plasma membrane potentials to more positive values. The sensitivity of these parameters to the energy deficit caused by the removal of glucose showed the following order: mitochondrial membrane potential > plasma membrane potential > pH gradient in synaptic vesicles. The latter was almost unaffected by deprivation compared with the control. The pH-dependent dye acridine orange was used to investigate synaptic vesicle recycling. However, the compound's fluorescence was shown to be enhanced also by the mixture of mitochondrial toxins rotenone (10 µM) and oligomycin (5 µg/mL). This means that acridine orange can presumably be partially distributed in the intermembrane space of mitochondria. Glucose removal from the incubation medium resulted in a 3.7-fold raise of acridine orange response to rotenone + oligomycin suggesting a dramatic increase in the mitochondrial pH gradient. Our results suggest that the biophysical characteristics of neuronal presynaptic endings do not favor excessive non-controlled neurotransmitter release in case of hypoglycemia. The inhibition of exocytosis and the increase of the mitochondrial pH gradient, while preserving the vesicular pH gradient, are proposed as compensatory mechanisms.

  15. A systematic review and meta-analysis to determine the contribution of mr imaging to the diagnosis of foetal brain abnormalities In Utero

    Energy Technology Data Exchange (ETDEWEB)

    Jarvis, Debbie; Griffiths, Paul D. [University of Sheffield, Academic Unit of Radiology, Sheffield (United Kingdom); Mooney, Cara; Cohen, Judith; Papaioannou, Diana; Bradburn, Mike; Sutton, Anthea [School of Health and Related Research (ScHARR) University of Sheffield, Sheffield (United Kingdom)

    2017-06-15

    This systematic review was undertaken to define the diagnostic performance of in utero MR (iuMR) imaging when attempting to confirm, exclude or provide additional information compared with the information provided by prenatal ultrasound scans (USS) when there is a suspicion of foetal brain abnormality. Electronic databases were searched as well as relevant journals and conference proceedings. Reference lists of applicable studies were also explored. Data extraction was conducted by two reviewers independently to identify relevant studies for inclusion in the review. Inclusion criteria were original research that reported the findings of prenatal USS and iuMR imaging and findings in terms of accuracy as judged by an outcome reference diagnosis for foetal brain abnormalities. 34 studies met the inclusion criteria which allowed diagnostic accuracy to be calculated in 959 cases, all of which had an outcome reference diagnosis determined by postnatal imaging, surgery or autopsy. iuMR imaging gave the correct diagnosis in 91 % which was an increase of 16 % above that achieved by USS alone. iuMR imaging makes a significant contribution to the diagnosis of foetal brain abnormalities, increasing the diagnostic accuracy achievable by USS alone. (orig.)

  16. The 1997 American Diabetes Association criteria versus the 1985 World Health Organization criteria for the diagnosis of abnormal glucose tolerance : poor agreement in the Hoorn Study

    NARCIS (Netherlands)

    de Vegt, F; Dekker, J M; Stehouwer, C D; Nijpels, G; Bouter, L M; Heine, R J

    1998-01-01

    OBJECTIVE: Recently, the American Diabetes Association (ADA) introduced new diagnostic criteria. These new criteria are based on fasting plasma glucose levels, avoiding the burdensome oral glucose tolerance test (OGTT). We compared the 1997 ADA criteria with the 1985 World Health Organization (WHO)

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

    Directory of Open Access Journals (Sweden)

    June Zhou

    2017-09-01

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

  18. Quantitative Rates of Brain Glucose Metabolism Distinguish Minimally Conscious from Vegetative State Patients

    DEFF Research Database (Denmark)

    Stender, Johan; Kupers, Ron; Rodell, Anders

    2015-01-01

    The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these......The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function...... cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were...

  19. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    Directory of Open Access Journals (Sweden)

    Hwang Jong-Hee

    2008-10-01

    Full Text Available Abstract Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap, effects on host cell protein processing (ubiquitin ligase, synapse remodeling (Complement 1q, and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease. Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of

  20. Immunocytochemical analysis of glucose transporter protein-1 (GLUT-1) in typical, brain invasive, atypical and anaplastic meningioma.

    Science.gov (United States)

    van de Nes, Johannes A P; Griewank, Klaus G; Schmid, Kurt-Werner; Grabellus, Florian

    2015-02-01

    Glucose transporter-1 (GLUT-1) is one of the major isoforms of the family of glucose transporter proteins that facilitates the import of glucose in human cells to fuel anaerobic metabolism. The present study was meant to determine the extent of the anaerobic/hypoxic state of the intratumoral microenvironment by staining for GLUT-1 in intracranial non-embolized typical (WHO grade I; n = 40), brain invasive and atypical (each WHO grade II; n = 38) and anaplastic meningiomas (WHO grade III, n = 6). In addition, GLUT-1 staining levels were compared with the various histological criteria used for diagnosing WHO grade II and III meningiomas, namely, brain invasion, increased mitotic activity and atypical cytoarchitectural change, defined by the presence of at least three out of hypercellularity, sheet-like growth, prominent nucleoli, small cell change and "spontaneous" necrosis. The level of tumor hypoxia was assessed by converting the extent and intensity of the stainings by multiplication in an immunoreactive score (IRS) and statistically evaluated. The results were as follows. (1) While GLUT-1 expression was found to be mainly weak in WHO grade I meningiomas (IRS = 1-4) and to be consistently strong in WHO grade III meningiomas (IRS = 6-12), in WHO grade II meningiomas GLUT-1 expression was variable (IRS = 1-9). (2) Histologically typical, but brain invasive meningiomas (WHO grade II) showed no or similarly low levels of GLUT-1 expression as observed in WHO grade I meningiomas (IRS = 0-4). (3) GLUT-1 expression was observed in the form of a patchy, multifocal staining reaction in 76% of stained WHO grade I-III meningiomas, while diffuse staining (in 11%) and combined multifocal and areas of diffuse staining (in 13%) were only detected in WHO grades II and III meningiomas, except for uniform staining in angiomatous WHO grade I meningioma. (4) "Spontaneous" necrosis and small cell change typically occurred away from the intratumoral capillary

  1. Diabetes mellitus and abnormal glucose tolerance development after gestational diabetes: A three-year, prospective, randomized, clinical-based, Mediterranean lifestyle interventional study with parallel groups.

    Science.gov (United States)

    Pérez-Ferre, Natalia; Del Valle, Laura; Torrejón, Maria José; Barca, Idoya; Calvo, María Isabel; Matía, Pilar; Rubio, Miguel A; Calle-Pascual, Alfonso L

    2015-08-01

    Women with prior gestational diabetes mellitus (GDM) have a high risk of developing type 2 diabetes mellitus (DM2) in later life. The study aim was to evaluate the efficacy of a lifestyle intervention for the prevention of glucose disorders (impaired fasting glucose, impaired glucose tolerance or DM2) in women with prior GDM. A total of 260 women with prior GDM who presented with normal fasting plasma glucose at six to twelve weeks postpartum were randomized into two groups: a Mediterranean lifestyle intervention group (n = 130) who underwent an educational program on nutrition and a monitored physical activity program and a control group (n = 130) with a conventional follow-up. A total of 237 women completed the three-year follow-up (126 in the intervention group and 111 in the control group). Their glucose disorders rates, clinical and metabolic changes and rates of adherence to the Mediterranean lifestyle were analyzed. Less women in the intervention group (42.8%) developed glucose disorders at the end of the three-year follow-up period compared with the control group (56.75%), p women with prior GDM. Body weight gain and an unhealthy fat intake pattern were found to be the most predictive factors for the development of glucose disorders. Current Controlled trials: ISRCTN24165302. http://www.controlled-trials.com/isrctn/pf/24165302. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  2. The oral administration of D-galactose induces abnormalities within the mitochondrial respiratory chain in the brain of rats.

    Science.gov (United States)

    Budni, Josiane; Garcez, Michelle Lima; Mina, Francielle; Bellettini-Santos, Tatiani; da Silva, Sabrina; Luz, Aline Pereira da; Schiavo, Gustavo Luiz; Batista-Silva, Hemily; Scaini, Giselli; Streck, Emílio Luiz; Quevedo, João

    2017-06-01

    D-Galactose (D-gal) chronic administration via intraperitoneal and subcutaneous routes has been used as a model of aging and Alzheimer disease in rodents. Intraperitoneal and subcutaneous administration of D-gal causes memory impairments, a reduction in the neurogenesis of adult mice, an increase in the levels of the amyloid precursor protein and oxidative damage; However, the effects of oral D-gal remain unclear. The aim of this study was to evaluate whether the oral administration of D-gal induces abnormalities within the mitochondrial respiratory chain of rats. Male Wistar rats (4 months old) received D-gal (100 mg/kg v.o.), during the 1st, 2nd, 4th, 6th or 8th weeks by oral gavage. The activity of the mitochondrial respiratory chain complexes was measured in the 1st, 2nd, 4th, 6th and 8th weeks after the administration of D-gal. The activity of the respiratory chain complex I was found to have increased in the prefrontal cortex and hippocampus in the 1st, 6th and 8th weeks, while the activity of the respiratory chain complex II increased in the 1st, 2nd, 4th, 6th and 8th weeks within the hippocampus and in the 2nd, 4th, 6th and 8th weeks within the prefrontal cortex. The activity of complex II-III increased within the prefrontal cortex and hippocampus in each week of oral D-gal treatment. The activity of complex IV increased within the prefrontal cortex and hippocampus in the 1st, 2nd, 6th and 8th weeks of treatment. After 4 weeks of treatment the activity increased only in hippocampus. In conclusion, the present study showed that the oral administration of D-gal increased the activity of the mitochondrial respiratory chain complexes I, II, II-III and IV in the prefrontal cortex and hippocampus. Furthermore, the administration of D-gal via the oral route seems to cause the alterations in the mitochondrial respiratory complexes observed in brain neurodegeneration.

  3. Correlation of Homocysteine with Cerebral Hemodynamic Abnormality, Endothelial Dysfunction Markers, and Cognition Impairment in Patients with Traumatic Brain Injury.

    Science.gov (United States)

    Hatefi, Masoud; Behzadi, Someyeh; Dastjerdi, Masoud Moghadas; Ghahnavieh, Alireza Abootalebi; Rahmani, Asghar; Mahdizadeh, Fatemeh; Hafezi Ahmadi, Mohammad Reza; Asadollahi, Khairollah

    2017-01-01

    This study aimed to assess any correlation between serum levels of homocysteine (Hcy) and markers of cerebral hemodynamics, endothelial dysfunction, and cognition impairment in patients with traumatic brain injury (TBI). By a cross-sectional study, all clinical data and serum levels of homocysteine of 85 TBI patients were collected. The pulsatility indices (PIs) of the middle cerebral artery were recorded by transcranial color-coded Doppler ultrasonography and cerebrovascular reactivity was measured by the increase in middle cerebral artery flow velocity in response to 5% inhaled CO 2 . Serum levels of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1), cognition status by Montreal Cognitive Assessment, and Mini-Mental State Examination were measured in all participants. Totally, 85 patients including 51.76% male and the mean age of 54.48 years were studied. The level of Hcy in patients who died in the hospital or during 6 months after TBI was significantly higher than in survivors (P = 0.045, P = 0.020, respectively). Also, the levels of ICAM-1, VCAM-1, and PI in deceased patients were higher than their figures in survivors in both hospital and 6-month follow-ups (P = 0.450, P = 0.000; P = 0.072, P = 0.000, P = 0.090, and P = 0.000, respectively). Cerebrovascular reactivity in deceased patients was significantly lower than that in alive individuals (P = 0.008 and P = 0.000, respectively). A significant correlation was found between Hcy with cognition impairment according to Montreal Cognitive Assessment, Mini-Mental State Examination, and cerebral hemodynamic status according to PI (P = 0.000 for all). Also, this correlation was shown between Hcy with ICAM-1 and VCAM-1 in hospital and 6-month follow-ups (P = 0.000 for both). Hcy has a significant correlation with markers of cerebrovascular, endothelial, and cognition abnormality in TBI patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

    International Nuclear Information System (INIS)

    Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana; Romanelli, Pantaleo; Giovacchini, Giampiero; Ciarmiello, Andrea; Frati, Luigi; Mansi, Luigi

    2009-01-01

    Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and 18 F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

  5. Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

    Energy Technology Data Exchange (ETDEWEB)

    Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana [IRCCS Neuromed, Neurogenetics Unit and Centre for Rare Disease, Pozzilli (Italy); Romanelli, Pantaleo [IRCCS Neuromed, Department of Neurosurgery, Pozzilli (Italy); Giovacchini, Giampiero; Ciarmiello, Andrea [S. Andrea Hospital, Unit of Nuclear Medicine, La Spezia (Italy); Frati, Luigi [University ' ' Sapienza' ' , Department of Experimental Medicine, Rome (Italy); Mansi, Luigi [Second University of Naples, Department of Nuclear Medicine, Naples (Italy)

    2009-07-15

    Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and {sup 18}F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

  6. Transient oxygen-glucose deprivation sensitizes brain capillary endothelial cells to rtPA at 4h of reoxygenation.

    Science.gov (United States)

    Kuntz, Mélanie; Mysiorek, Caroline; Pétrault, Olivier; Boucau, Marie-Christine; Aijjou, Rachid; Uzbekov, Rustem; Bérézowski, Vincent

    2014-01-01

    Thrombolysis treatment of acute ischemic stroke is limited by the pro-edematous and hemorrhagic effects exerted by reperfusion, which disrupts the blood-brain barrier (BBB) capillary endothelium in the infarct core. Most studies of the ischemic BBB overlook the complexity of the penumbral area, where the affected brain cells are still viable following deprivation. Our present objective was to examine in vitro the kinetic impact of reoxygenation on the integrity of ischemic BBB cells after oxygen-glucose deprivation. Through the use of a co-culture of brain capillary endothelial cells and glial cells, we first showed that the transendothelial permeability increase induced by deprivation can occur with both preserved cell viability and interendothelial tight junction network. The subtle and heterogeneous alteration of the tight junctions was observable only through electron microscopy. A complete permeability recovery was then found after reoxygenation, when Vimentin and Actin networks were reordered. However, still sparse ultrastructural alterations of tight junctions suggested an acquired vulnerability. Endothelial cells were then exposed to recombinant tissue-type plasminogen activator (rtPA) to define a temporal profile for the toxic effect of this thrombolytic on transendothelial permeability. Interestingly, the reoxygenated BBB broke down with aggravated tight junction disruption when exposed to rtPA only at 4h after reoxygenation. Moreover, this breakdown was enhanced by 50% when ischemic glial cells were present during the first hours of reoxygenation. Our results suggest that post-stroke reoxygenation enables retrieval of the barrier function of brain capillary endothelium when in a non-necrotic environment, but may sensitize it to rtPA at the 4-hour time point, when both endothelial breakdown mechanisms and glial secretions could be identified and targeted in a therapeutical perspective. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Altered brain activity in women recovered from bulimic-type eating disorders after a glucose challenge: a pilot study.

    Science.gov (United States)

    Frank, Guido K; Wagner, Angela; Achenbach, Sarah; McConaha, Claire; Skovira, Kellie; Aizenstein, Howard; Carter, Cameron S; Kaye, Walter H

    2006-01-01

    It is not known whether individuals with bulimic-type eating disorders have a dysregulation of brain pathways that modulate appetite. Taste plays a role in the regulation of appetite and the purpose of the current study was to determine whether bulimic women have alterations in the physiologic response to the blind administration of glucose. To avoid the confounding effects of a current eating disorder, and to assess possibly trait-related disturbances, we studied 10 subjects recovered (> or = 1 year) from a bulimic-type eating disorder and 6 control women. Subjects were administered a solution of glucose or artificial saliva (control solution) in alternating blocks during a functional magnet resonance imaging scan. Individuals who recovered from a bulimic-type eating disorder had significantly lower activation in the right anterior cingulate cortex (ACC; Montreal Neurological Institute [MNI] coordinates x = 8, y = 22, z = 28; cluster size = 18 voxels, T = 5.11, Z-score = 3.78) and in the left cuneus (occipital cortex; MNI coordinates x = -12, y = -78, z = 10; cluster size = 21 voxels, T = 4.27, Z-score = 3.36), when glucose was compared with artificial saliva. The ACC plays a role in the anticipation of reward. Individuals with bulimic-type eating disorders may have a reduced reward response to nutrients, and thus may be vulnerable to overeating. However, this is a small sample and the current study will need replication in a larger sample size with investigation of additional regions of interest. 2005 by Wiley Periodicals, Inc.

  8. Regulation of Brain Glucose Metabolic Patterns by Protein Phosphorlyation and Drug Therapy

    Science.gov (United States)

    2007-03-30

    Bipolar GLU cell • ®.-. GLN Figure 3. Diagrammatic representation ofthe metabolic stuttering oflactate between glia and photoreceptors in the retina...film. Films were digitized and the resulting images were analyzed using ImageJ software . Two Dimensional Gel Electrophoresis Rat brain mitochondria were

  9. Voxel-based comparison of brain glucose metabolism between patients with Cushing's disease and healthy subjects

    Directory of Open Access Journals (Sweden)

    Shuai Liu

    2018-01-01

    Full Text Available Cognitive impairment and psychiatric symptoms are common in patients with Cushing's disease (CD owing to elevated levels of glucocorticoids. Molecular neuroimaging methods may help to detect changes in the brain of patients with CD. The aim of this study was to investigate the characteristics of brain metabolism and its association with serum cortisol level in CD. We compared brain metabolism, as measured using [18F]-fluorodeoxyglucose positron emission tomography (FDG PET, between 92 patients with CD and 118 normal subjects on a voxel-wise basis. Pearson correlation was performed to evaluate the association between cerebral FDG uptake and serum cortisol level in patients with CD. We demonstrated that certain brain regions in patients with CD showed significantly increased FDG uptake, including the basal ganglia, anteromedial temporal lobe, thalamus, precentral cortex, and cerebellum. The clusters that demonstrated significantly decreased uptake were mainly located in the medial and lateral frontal cortex, superior and inferior parietal lobule, medial occipital cortex, and insular cortex. The metabolic rate of the majority of these regions was found to be significantly correlated with the serum cortisol level. Our findings may help to explain the underlying mechanisms of cognitive impairment and psychiatric symptoms in patients exposed to excessive glucocorticoids and evaluate the efficacy of treatments during follow-up.

  10. Tritiated 2-deoxy-D-glucose: a high-resolution marker for autoradiographic localization of brain metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Hammer, R.P. Jr.; Herkenham, M.

    1984-01-01

    The technique for autoradiographic localization of 2-deoxy-D-glucose (2DG) uptake has become a useful method for observing alterations of functional brain activity resulting from experimental manipulation. Autoradiographic resolution is improved using tritiated ((3H)) rather than carbon-14 ((14C))2DG, due to the lower energy and shorter path of tritium emissions. In addition, lower 2DG uptake by white matter relative to gray matter is exaggerated in the (3H)2DG autoradiographs due to the greater absorption of tritium emissions by lipids. Using (3H)2DG, it is possible to observe differential metabolic labeling in various individual nuclei or portions of nuclei that is unresolvable using (14C)2DG in the awake, normal animal. Heterogeneous patterns of 2DG uptake seen only with (3H)2DG are found in the nucleus accumbens, the anterior portion of the basolateral nucleus of the amygdala, specific nuclei of the inferior olivary complex, various hypothalamic regions, and a region straddling the border of the medial and lateral habenular nuclei. The lamination of differential 2DG uptake in the hippocampus is better localized using (3H)2DG. Autoradiographic resolution of labeled 2DG is further improved when the brain is perfused prior to frozen sectioning, due perhaps to selective fixation and retention of intracellular labeled 2-deoxy-glycogen. A series of (3H)2DG autoradiographs are presented together with views of the Nissl-stained sections that produced the autoradiographs.

  11. Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain

    Directory of Open Access Journals (Sweden)

    Minchenko Dimitri

    2010-04-01

    Full Text Available Abstract Background The Rett Syndrome (RTT brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results Using microarrays and quantitative PCR, the mRNA expression profiles of these two neuroanatomical regions were compared in postmortem brain tissue from RTT patients and normal controls. A subset of genes was differentially expressed in the frontal cortex of RTT brains, some of which are known to be associated with neurological disorders (clusterin and cytochrome c oxidase subunit 1 or are involved in synaptic vesicle cycling (dynamin 1. RNAi-mediated knockdown of MeCP2 in vitro, followed by further expression analysis demonstrated that the same direction of abnormal expression was recapitulated with MeCP2 knockdown, which for cytochrome c oxidase subunit 1 was associated with a functional respiratory chain defect. Chromatin immunoprecipitation (ChIP analysis showed that MeCP2 associated with the promoter regions of some of these genes suggesting that loss of MeCP2 function may be responsible for their overexpression. Conclusions This study has shed more light on the subset of aberrantly expressed genes that result from MECP2 mutations. The mitochondrion has long been implicated in the pathogenesis of RTT, however it has not been at the forefront of RTT research interest since the discovery of MECP2 mutations. The functional consequence of the underexpression of cytochrome c oxidase subunit 1 indicates that this is an area that should be revisited.

  12. A sequential two meal challenge reveals abnormalities in postprandial TAG but not glucose in men with increasing numbers of metabolic syndrome components.

    Science.gov (United States)

    Jackson, Kim G; Walden, Charlotte M; Murray, Peter; Smith, Adrian M; Lovegrove, Julie A; Minihane, Anne M; Williams, Christine M

    2012-01-01

    To examine the impact of increasing numbers of metabolic syndrome (MetS) components on postprandial lipaemia. Healthy men (n=112) underwent a sequential meal postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast (0min) and lunch (330min). Lipids, glucose and insulin were measured in the fasting sample, with triacylglycerol (TAG), non-esterified fatty acids and glucose analysed in the postprandial samples. Subjects were grouped according to the number of MetS components regardless of the combinations of components (0/1, 2, 3 and 4/5). As expected, there was a trend for an increase in body mass index, blood pressure, fasting TAG, glucose and insulin, and a decrease in fasting high-density lipoprotein cholesterol with increasing numbers of MetS components (P≤0.0004). A similar trend was observed for the summary measures of the postprandial TAG and glucose responses. For TAG, the area under the curve (AUC) and maximum concentration (maxC) were significantly greater in men with ≥3 than postprandial TAG and glucose responses. Furthermore, the two meal challenge discriminated a worsening of postprandial lipaemic control in subjects with ≥3 MetS components. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. The Common C49620T Polymorphism in the Sulfonylurea Receptor Gene SUR1 (ABCC8) in Patients with Gestational Diabetes and Subsequent Glucose Metabolism Abnormalities

    Science.gov (United States)

    Molęda, Piotr; Bińczak-Kuleta, Agnieszka; Homa, Katarzyna; Safranow, Krzysztof; Celewicz, Zbigniew; Syrenicz, Anhelli; Stefański, Adam; Fronczyk, Aneta; Majkowska, Lilianna

    2012-01-01

    Aim. The aim of this study is to investigate the relationship between the common C49620T polymorphism in the sulfonylurea receptor (SUR1) gene and glucose metabolism, β-cell secretory function and insulin resistance in women with a history of gestational diabetes (GDM). Material and Methods. Study group included 199 women, diagnosed GDM within the last 5–12 years and control group of comparable 50 women in whom GDM was excluded during pregnancy. Blood glucose and insulin levels were measured during oral glucose tolerance test. Indices of insulin resistance (HOMA-IR) and β-cell function (HOMA %B) were calculated. In all patients, the C49620T polymorphism in intron 15 of the SUR1 gene was determined. Results. The distribution of the studied polymorphism in the two groups did not differ from each other (χ 2 = 0.34, P = 0.8425). No association between the distribution of polymorphisms and coexisting glucose metabolism disorders (χ 2 = 7,13, P = 0, 3043) was found. No association was also observed between the polymorphism and HOMA %B or HOMA-IR. Conclusions. The polymorphism C49620T in the SUR1 gene is not associated with insulin resistance and/or insulin secretion in women with a history of GDM and does not affect the development of GDM, or the development of glucose intolerance in the studied population. PMID:22927833

  14. Abnormal pain processing in chronic tension-type headache: a high-density EEG brain mapping study

    DEFF Research Database (Denmark)

    Buchgreitz, L.; Egsgaard, L.L.; Jensen, R.

    2008-01-01

    Central sensitization caused by prolonged nociceptive input from muscles is considered to play an important role for chronification of tension-type headache. In the present study we used a new high-density EEG brain mapping technique to investigate spatiotemporal aspects of brain activity...

  15. Resting-state EEG oscillatory dynamics in fragile X syndrome: abnormal functional connectivity and brain network organization.

    Directory of Open Access Journals (Sweden)

    Melle J W van der Molen

    Full Text Available Disruptions in functional connectivity and dysfunctional brain networks are considered to be a neurological hallmark of neurodevelopmental disorders. Despite the vast literature on functional brain connectivity in typical brain development, surprisingly few attempts have been made to characterize brain network integrity in neurodevelopmental disorders. Here we used resting-state EEG to characterize functional brain connectivity and brain network organization in eight males with fragile X syndrome (FXS and 12 healthy male controls. Functional connectivity was calculated based on the phase lag index (PLI, a non-linear synchronization index that is less sensitive to the effects of volume conduction. Brain network organization was assessed with graph theoretical analysis. A decrease in global functional connectivity was observed in FXS males for upper alpha and beta frequency bands. For theta oscillations, we found increased connectivity in long-range (fronto-posterior and short-range (frontal-frontal and posterior-posterior clusters. Graph theoretical analysis yielded evidence of increased path length in the theta band, suggesting that information transfer between brain regions is particularly impaired for theta oscillations in FXS. These findings are discussed in terms of aberrant maturation of neuronal oscillatory dynamics, resulting in an imbalance in excitatory and inhibitory neuronal circuit activity.

  16. In Alzheimer's disease, 6-month treatment with GLP-1 analog prevents decline of brain glucose metabolism

    DEFF Research Database (Denmark)

    Gejl, Michael; Gjedde, Albert; Egefjord, Lærke

    2016-01-01

    with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [11C]PIB (PIB), CMRglc with [18F]FDG (FDG), and cognition with the WMS-IV scale (ClinicalTrials.gov NCT01469351). The PIB binding increased significantly in temporal lobe...... in placebo and treatment patients (both P = 0.04), and in occipital lobe in treatment patients (P = 0.04). Regional and global increases of PIB retention did not differ between the groups (P ≥ 0.38). In placebo treated patients CMRglc declined in all regions, significantly so by the following means...

  17. Structural and Functional Brain Abnormalities in Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder: A Comparative Meta-analysis.

    Science.gov (United States)

    Norman, Luke J; Carlisi, Christina; Lukito, Steve; Hart, Heledd; Mataix-Cols, David; Radua, Joaquim; Rubia, Katya

    2016-08-01

    Patients with attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) share impaired inhibitory control. However, it is unknown whether impairments are mediated by shared or disorder-specific neurostructural and neurofunctional abnormalities. To establish shared and disorder-specific structural, functional, and overlapping multimodal abnormalities in these 2 disorders through a voxel-based meta-analytic comparison of whole-brain gray matter volume (GMV) and functional magnetic resonance imaging (fMRI) studies of inhibition in patients with ADHD and OCD. Literature search using PubMed, ScienceDirect, Web of Knowledge, and Scopus up to September 30, 2015. Whole-brain voxel-based morphometry (VBM) or fMRI studies during inhibitory control comparing children and adults with ADHD or OCD with controls. Voxel-wise meta-analyses of GMV or fMRI differences were performed using Seed-based d-Mapping. Regional structure and function abnormalities were assessed within each patient group and then a quantitative comparison was performed of abnormalities (relative to controls) between ADHD and OCD. Meta-analytic disorder-specific and shared abnormalities in GMV, in inhibitory fMRI, and in multimodal functional and structural measures. The search revealed 27 ADHD VBM data sets (including 931 patients with ADHD and 822 controls), 30 OCD VBM data sets (928 patients with OCD and 942 controls), 33 ADHD fMRI data sets (489 patients with ADHD and 591 controls), and 18 OCD fMRI data sets (287 patients with OCD and 284 controls). Patients with ADHD showed disorder-contrasting multimodal structural (left z = 1.904, P disorder-specific reduced function and structure in rostral and dorsal anterior cingulate/medial prefrontal cortex (fMRI z = 2.113, P disorder-specific underactivation predominantly in the right ventrolateral prefrontal cortex (z = 1.229, P disorders relative to controls. Shared impairments in inhibitory control, rather

  18. Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study.

    Science.gov (United States)

    Courchesne-Loyer, Alexandre; Croteau, Etienne; Castellano, Christian-Alexandre; St-Pierre, Valérie; Hennebelle, Marie; Cunnane, Stephen C

    2017-07-01

    Ketones (principally β-hydroxybutyrate and acetoacetate (AcAc)) are an important alternative fuel to glucose for the human brain, but their utilisation by the brain remains poorly understood. Our objective was to use positron emission tomography (PET) to assess the impact of diet-induced moderate ketosis on cerebral metabolic rate of acetoacetate (CMRa) and glucose (CMRglc) in healthy adults. Ten participants (35 ± 15 y) received a very high fat ketogenic diet (KD) (4.5:1; lipid:protein plus carbohydrates) for four days. CMRa and CMRglc were quantified by PET before and after the KD with the tracers, 11 C-AcAc and 18 F-fluorodeoxyglucose ( 18 F-FDG), respectively. During the KD, plasma ketones increased 8-fold ( p = 0.005) while plasma glucose decreased by 24% ( p = 0.005). CMRa increased 6-fold ( p = 0.005), whereas CMRglc decreased by 20% ( p = 0.014) on the KD. Plasma ketones were positively correlated with CMRa (r = 0.93; p < 0.0001). After four days on the KD, CMRa represented 17% of whole brain energy requirements in healthy adults with a 2-fold difference across brain regions (12-24%). The CMR of ketones (AcAc and β-hydroxybutyrate combined) while on the KD was estimated to represent about 33% of brain energy requirements or approximately double the CMRa. Whether increased ketone availability raises CMR of ketones to the same extent in older people as observed here or in conditions in which chronic brain glucose hypometabolism is present remains to be determined.

  19. Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography.

    Science.gov (United States)

    Wegner, Florian; Wilke, Florian; Raab, Peter; Tayeb, Said Ben; Boeck, Anna-Lena; Haense, Cathleen; Trebst, Corinna; Voss, Elke; Schrader, Christoph; Logemann, Frank; Ahrens, Jörg; Leffler, Andreas; Rodriguez-Raecke, Rea; Dengler, Reinhard; Geworski, Lilli; Bengel, Frank M; Berding, Georg; Stangel, Martin; Nabavi, Elham

    2014-06-20

    Pathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis. The brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls. Group analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism. This retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.

  20. Influence of P-Glycoprotein Inhibition or Deficiency at the Blood-Brain Barrier on (18)F-2-Fluoro-2-Deoxy-D-glucose ( (18)F-FDG) Brain Kinetics.

    Science.gov (United States)

    Tournier, Nicolas; Saba, Wadad; Goutal, Sébastien; Gervais, Philippe; Valette, Héric; Scherrmann, Jean-Michel; Bottlaender, Michel; Cisternino, Salvatore

    2015-05-01

    The fluorinated D-glucose analog (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) is the most prevalent radiopharmaceutical for positron emission tomography (PET) imaging. P-Glycoprotein's (P-gp, MDR1, and ABCB1) function in various cancer cell lines and tumors was shown to impact (18)F-FDG incorporation, suggesting that P-gp function at the blood-brain barrier may also modulate (18)F-FDG brain kinetics. We tested the influence of P-gp inhibition using the cyclosporine analog valspodar (PSC833; 5 μM) on the uptake of (18)F-FDG in standardized human P-gp-overexpressing cells (MDCKII-MDR1). Consequences for (18)F-FDG brain kinetics were then assessed using (i) (18)F-FDG PET imaging and suitable kinetic modelling in baboons without or with P-gp inhibition by intravenous cyclosporine infusion (15 mg kg(-1) h(-1)) and (ii) in situ brain perfusion in wild-type and P-gp/Bcrp (breast cancer resistance protein) knockout mice and controlled D-glucose exposure to the brain. In vitro, the time course of (18)F-FDG uptake in MDR1 cells was influenced by the presence of valspodar in the absence of D-glucose but not in the presence of high D-glucose concentration. PET analysis revealed that P-gp inhibition had no significant impact on estimated brain kinetics parameters K 1, k 2, k 3, V T , and CMRGlc. The lack of P-gp effect on in vivo (18)F-FDG brain distribution was confirmed in P-gp/Bcrp-deficient mice. P-gp inhibition indirectly modulates (18)F-FDG uptake into P-gp-overexpressing cells, possibly through differences in the energetic cell level state. (18)F-FDG is not a P-gp substrate at the BBB and (18)F-FDG brain kinetics as well as estimated brain glucose metabolism are influenced by neither P-gp inhibition nor P-gp/Bcrp deficiencies in baboon and mice, respectively.

  1. Relation of measured brain glucose utilisation and cerebral atrophy in man.

    Science.gov (United States)

    Schlageter, N L; Horwitz, B; Creasey, H; Carson, R; Duara, R; Berg, G W; Rapoport, S I

    1987-06-01

    The effect of cerebral atrophy on measured cerebral metabolic rates for glucose (CMRglc), as determined with positron emission tomography (PET), was examined in 49 healthy males aged 21-83 years. Global CMRglc and regional CMRglc for 34 grey matter regions parallel to and from 30 to 80 mm above the inferior orbital meatal (IOM) line were measured under resting conditions, using [18F]-fluorodeoxyglucose and an ECAT II positron emission tomograph. Using a GE 8800 CT/T scanner, slices parallel to and from 30 to 80 mm above the IOM line were analysed for CSF volume. Cerebral atrophy, indicated by increased CSF volume, was correlated significantly with global CMRglc, but accounted for no more than 13% of the variance in the CMRglc measurements. Methods for correcting for inter-subject variation in CSF volume were proposed. Global values for CMRglc, uncorrected or corrected for CSF volume, were found to be age invariant. These findings indicate that (a) cerebral atrophy has a small, but statistically significant effect on CMRglc as measured with PET; (b) CMRglc is age invariant in healthy males.

  2. An improved FSL-FIRST pipeline for subcortical gray matter segmentation to study abnormal brain anatomy using quantitative susceptibility mapping (QSM).

    Science.gov (United States)

    Feng, Xiang; Deistung, Andreas; Dwyer, Michael G; Hagemeier, Jesper; Polak, Paul; Lebenberg, Jessica; Frouin, Frédérique; Zivadinov, Robert; Reichenbach, Jürgen R; Schweser, Ferdinand

    2017-06-01

    Accurate and robust segmentation of subcortical gray matter (SGM) nuclei is required in many neuroimaging applications. FMRIB's Integrated Registration and Segmentation Tool (FIRST) is one of the most popular software tools for automated subcortical segmentation based on T 1 -weighted (T1w) images. In this work, we demonstrate that FIRST tends to produce inaccurate SGM segmentation results in the case of abnormal brain anatomy, such as present in atrophied brains, due to a poor spatial match of the subcortical structures with the training data in the MNI space as well as due to insufficient contrast of SGM structures on T1w images. Consequently, such deviations from the average brain anatomy may introduce analysis bias in clinical studies, which may not always be obvious and potentially remain unidentified. To improve the segmentation of subcortical nuclei, we propose to use FIRST in combination with a special Hybrid image Contrast (HC) and Non-Linear (nl) registration module (HC-nlFIRST), where the hybrid image contrast is derived from T1w images and magnetic susceptibility maps to create subcortical contrast that is similar to that in the Montreal Neurological Institute (MNI) template. In our approach, a nonlinear registration replaces FIRST's default linear registration, yielding a more accurate alignment of the input data to the MNI template. We evaluated our method on 82 subjects with particularly abnormal brain anatomy, selected from a database of >2000 clinical cases. Qualitative and quantitative analyses revealed that HC-nlFIRST provides improved segmentation compared to the default FIRST method. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Brain glucose metabolism in the early and specific diagnosis of Alzheimer's disease. FDG-PET studies in MCI and AD

    International Nuclear Information System (INIS)

    Mosconi, Lisa

    2005-01-01

    The demographics of aging suggest a great need for the early diagnosis of dementia and the development of preventive strategies. Neuropathology and structural MRI studies have pointed to the medial temporal lobe (MTL) as the brain region earliest affected in Alzheimer's disease (AD). MRI findings provide strong evidence that in mild cognitive impairments (MCI), AD-related volume losses can be reproducibly detected in the hippocampus, the entorhinal cortex (EC) and, to a lesser extent, the parahippocampal gyrus; they also indicate that lateral temporal lobe changes are becoming increasingly useful in predicting the transition to dementia. Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) imaging has revealed glucose metabolic reductions in the parieto-temporal, frontal and posterior cingulate cortices to be the hallmark of AD. Overall, the pattern of cortical metabolic changes has been useful for the prediction of future AD as well as in distinguishing AD from other neurodegenerative diseases. FDG-PET on average achieves 90% sensitivity in identifying AD, although specificity in differentiating AD from other dementias is lower. Moreover, recent MRI-guided FDG-PET studies have shown that MTL hypometabolism is the most specific and sensitive measure for the identification of MCI, while the utility of cortical deficits is controversial. This review highlights cross-sectional, prediction and longitudinal FDG-PET studies and attempts to put into perspective the value of FDG-PET in diagnosing AD-like changes, particularly at an early stage, and in providing diagnostic specificity. The examination of MTL structures, which has so far been exclusive to MRI protocols, is then examined as a possible strategy to improve diagnostic specificity. All told, there is considerable promise that early and specific diagnosis is feasible through a combination of imaging modalities. (orig.)

  4. Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism.

    Science.gov (United States)

    Chen, Tzu-Ling; Yang, Hung-Chi; Hung, Cheng-Yu; Ou, Meng-Hsin; Pan, Yi-Yun; Cheng, Mei-Ling; Stern, Arnold; Lo, Szecheng J; Chiu, Daniel Tsun-Yee

    2017-01-12

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly pervasive inherited disease in many parts of the world. The complete lack of G6PD activity in a mouse model causes embryonic lethality. The G6PD-deficient Caenorhabditis elegans model also shows embryonic death as indicated by a severe hatching defect. Although increased oxidative stress has been implicated in both cases as the underlying cause, the exact mechanism has not been clearly delineated. In this study with C. elegans, membrane-associated defects, including enhanced permeability, defective polarity and cytokinesis, were found in G6PD-deficient embryos. The membrane-associated abnormalities were accompanied by impaired eggshell structure as evidenced by a transmission electron microscopic study. Such loss of membrane structural integrity was associated with abnormal lipid composition as lipidomic analysis revealed that lysoglycerophospholipids were significantly increased in G6PD-deficient embryos. Abnormal glycerophospholipid metabolism leading to defective embryonic development could be attributed to the increased activity of calcium-independent phospholipase A 2 (iPLA) in G6PD-deficient embryos. This notion is further supported by the fact that the suppression of multiple iPLAs by genetic manipulation partially rescued the embryonic defects in G6PD-deficient embryos. In addition, G6PD deficiency induced disruption of redox balance as manifested by diminished NADPH and elevated lipid peroxidation in embryos. Taken together, disrupted lipid metabolism due to abnormal redox homeostasis is a major factor contributing to abnormal embryonic development in G6PD-deficient C. elegans.

  5. 18F-fluorodeoxyglucose accumulation in the heart, brain and skeletal muscle of rats; the influence of time after injection, depressed lipid metabolism and glucose-insulin

    International Nuclear Information System (INIS)

    Kasalicky, J.; Konopkova, M.; Melichar, F.

    2001-01-01

    To study the effect of lipid depressing drugs on 18 FDG myocardial concentration. The changes of 18 FDG uptake in myocardium, brain and skeletal muscle of rats were compared as influenced by acipimox, tyloxapol and glucose with insulin. 5.55 MBq of 18 FDG were administered to Wistar rats. Control rats were killed 15, 30, 45 and 60 minutes following intravenous injection and the radioactivity concentration (cpm/g of tissue) in relation to injected cpm was determined in a well crystal adjusted to 511 KeV in order to check the time of maximal 18 FDG tissue uptake. The radioactivity in myocardium, skeletal muscle and brain in intact animals was compared with that of rats treated with tyloxapol (tritton WR 1339, 125 mg intravenously immediately before 18 FDG injection), acipimox (nicotinic acid derivative, 25 mg by stomach cannula 15 minutes before 18 FDG), or glucose with insulin (intravenous injection of 0.04 g and 0.04 UI immediately before 18 FDG). The animals were killed 45 minutes following 18 FDG injection. Tyloxapol and acipimox significantly elevated myocardial 18 FDG concentration (tyloxapol +37% and acipimox +48%), but the increase in 18 FDG concentration after glucose and insulin was slight and insignificant. The changes in skeletal muscle after lipid depressing agents were quite contrasting; the decrease in 18 FDG concentration was -74% after tyloxapol and -44% following acipimox administration. The accumulation of 18 FDG in brain was not influenced markedly by the drugs used or by glucose with insulin. The highest 18 FDG uptake in myocardium could be achieved by depressing the lipid metabolism and not by administration of glucose with insulin only. A marked increase in glucose accumulation in myocardium is not possible without previous shift from the utilisation of fatty acids. This finding is fully in agreement with present knowledge about energetic metabolism of myocardium. (author)

  6. Abnormal blood-brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI

    DEFF Research Database (Denmark)

    Cramer, Stig Præstekær; Simonsen, Helle Juhl; Frederiksen, Jette Lautrup Battistini

    2013-01-01

    To investigate whether blood-brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics.......To investigate whether blood-brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics....

  7. FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer's disease

    International Nuclear Information System (INIS)

    Mosconi, Lisa; Mistur, Rachel; Switalski, Remigiusz; Glodzik, Lidia; Li, Yi; Pirraglia, Elizabeth; De Santi, Susan; Reisberg, Barry; Tsui, Wai Hon; De Leon, Mony J.; Wisniewski, Thomas

    2009-01-01

    We report the first clinicopathological series of longitudinal FDG-PET scans in post-mortem (PM) verified cognitively normal elderly (NL) followed to the onset of Alzheimer's-type dementia (DAT), and in patients with mild DAT with progressive cognitive deterioration. Four NL subjects and three patients with mild DAT received longitudinal clinical, neuropsychological and dynamic FDG-PET examinations with arterial input functions. NL subjects were followed for 13 ± 5 years, received FDG-PET examinations over 7 ± 2 years, and autopsy 6 ± 3 years after the last FDG-PET. Two NL declined to mild cognitive impairment (MCI), and two developed probable DAT before death. DAT patients were followed for 9 ± 3 years, received FDG-PET examinations over 3 ± 2 years, and autopsy 7 ± 1 years after the last FDG-PET. Two DAT patients progressed to moderate-to-severe dementia and one developed vascular dementia. The two NL subjects who declined to DAT received a PM diagnosis of definite AD. Their FDG-PET scans indicated a progression of deficits in the cerebral metabolic rate for glucose (CMRglc) from the hippocampus to the parietotemporal and posterior cingulate cortices. One DAT patient showed AD with diffuse Lewy body disease (LBD) at PM, and her last in vivo PET was indicative of possible LBD for the presence of occipital as well as parietotemporal hypometabolism. Progressive CMRglc reductions on FDG-PET occur years in advance of clinical DAT symptoms in patients with pathologically verified disease. The FDG-PET profiles in life were consistent with the PM diagnosis. (orig.)

  8. Glucose Metabolic Changes in the Brain and Muscles of Patients with Nonspecific Neck Pain Treated by Spinal Manipulation Therapy: A [18F]FDG PET Study

    Directory of Open Access Journals (Sweden)

    Akie Inami

    2017-01-01

    Full Text Available Objective. The aim of this study was to investigate changes in brain and muscle glucose metabolism that are not yet known, using positron emission tomography with [18F]fluorodeoxyglucose ([18F]FDG PET. Methods. Twenty-one male volunteers were recruited for the present study. [18F]FDG PET scanning was performed twice on each subject: once after the spinal manipulation therapy (SMT intervention (treatment condition and once after resting (control condition. We performed the SMT intervention using an adjustment device. Glucose metabolism of the brain and skeletal muscles was measured and compared between the two conditions. In addition, we measured salivary amylase level as an index of autonomic nervous system (ANS activity, as well as muscle tension and subjective pain intensity in each subject. Results. Changes in brain activity after SMT included activation of the dorsal anterior cingulate cortex, cerebellar vermis, and somatosensory association cortex and deactivation of the prefrontal cortex and temporal sites. Glucose uptake in skeletal muscles showed a trend toward decreased metabolism after SMT, although the difference was not significant. Other measurements indicated relaxation of cervical muscle tension, decrease in salivary amylase level (suppression of sympathetic nerve activity, and pain relief after SMT. Conclusion. Brain processing after SMT may lead to physiological relaxation via a decrease in sympathetic nerve activity.

  9. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    Directory of Open Access Journals (Sweden)

    Elena Lima-Cabello

    2016-01-01

    Full Text Available Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

  10. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    Science.gov (United States)

    Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes

    2016-01-01

    Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome. PMID:26788253

  11. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability.

    Science.gov (United States)

    Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes; de Diego-Otero, Yolanda

    2016-01-01

    Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

  12. Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments.

    Directory of Open Access Journals (Sweden)

    Kimberly B Zumbrennen-Bullough

    Full Text Available Iron Regulatory Protein 2 (Irp2, Ireb2 is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2-/- mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc, expression are increased and decreased, respectively, in the brain from Irp2-/- mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments.

  13. Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Waldman, A.D.; Cordery, R.J.; Godbolt, A.; Rossor, M.N.; MacManus, D.G.; Collinge, J.

    2006-01-01

    Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Straeussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. (orig.)

  14. Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Waldman, A.D.; Cordery, R.J.; Godbolt, A.; Rossor, M.N. [University College London, Dementia Research Group, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom); Imperial College of Science, Technology and Medicine, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, London (United Kingdom); MacManus, D.G. [University College London, NMR Research Unit, Department of Clinical Neurology, Institute of Neurology, London (United Kingdom); Collinge, J. [University College London, MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom)

    2006-06-15

    Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Straeussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. (orig.)

  15. Association between abnormal brain functional connectivity in children and psychopathology: A study based on graph theory and machine learning.

    Science.gov (United States)

    Sato, João Ricardo; Biazoli, Claudinei Eduardo; Salum, Giovanni Abrahão; Gadelha, Ary; Crossley, Nicolas; Vieira, Gilson; Zugman, André; Picon, Felipe Almeida; Pan, Pedro Mario; Hoexter, Marcelo Queiroz; Amaro, Edson; Anés, Mauricio; Moura, Luciana Monteiro; Del'Aquilla, Marco Antonio Gomes; Mcguire, Philip; Rohde, Luis Augusto; Miguel, Euripedes Constantino; Jackowski, Andrea Parolin; Bressan, Rodrigo Affonseca

    2018-03-01

    One of the major challenges facing psychiatry is how to incorporate biological measures in the classification of mental health disorders. Many of these disorders affect brain development and its connectivity. In this study, we propose a novel method for assessing brain networks based on the combination of a graph theory measure (eigenvector centrality) and a one-class support vector machine (OC-SVM). We applied this approach to resting-state fMRI data from 622 children and adolescents. Eigenvector centrality (EVC) of nodes from positive- and negative-task networks were extracted from each subject and used as input to an OC-SVM to label individual brain networks as typical or atypical. We hypothesised that classification of these subjects regarding the pattern of brain connectivity would predict the level of psychopathology. Subjects with atypical brain network organisation had higher levels of psychopathology (p EVC in the typical group at the bilateral posterior cingulate and bilateral posterior temporal cortices; and significant decreases in EVC at left temporal pole. The combination of graph theory methods and an OC-SVM is a promising method to characterise neurodevelopment, and may be useful to understand the deviations leading to mental disorders.

  16. Role of 99mTc-ECD brain SPECT in the detection of cerebral perfusion abnormality in cases of Attention Deficit Hyperactivity Disorder

    International Nuclear Information System (INIS)

    Kumar, A.; Phom, H.; Thomas, E.J.; Tripathi, M.; Chandrashekar, N.; Bal, C.S.; Zamir, H.; Gulati, S.; Kalra, V.

    2002-01-01

    Aim: A randomized placebo controlled drug trial with Mentat, a herbal pharmacological agent, was initiated in January 2000 in the department of pediatrics at AIIMS, New Delhi, to compare the efficacy of Mentat with a placebo in school children with Attention Deficit Hyperactivity Disorder (ADHD). Materials and Methods: Contact was established with 12 Public schools in Delhi, to identify poor performers in classes I-V (age 6-12 yrs.). About 195 children with poor school performance were recruited in the study. They were screened for causes of poor performance, which included attention problems, hyperactivity, behavior problems, emotional problems, mental sub-normality and learning disability. ADHD suspected children were identified using the Malin's WISC, Connor's rating scale, Problem Behavior checklist, Bender Gestalt test and some sub tests of the Kaufman's Assessment Battery for Children (K-ABC). Sixty children diagnosed as ADHD (using DSM-IV criteria), with an IQ between 90-110, were enrolled into the study. Of the 60 children randomized in the study, 30 received Mentat and 30 received an identical looking placebo. The drug/Placebo was given for a six-month period. 99mTC-ECD brain SPECT was performed in a subset of 34 children with ADHD. Results: Abnormal cerebral perfusion was seen in 23/34; thalamic hypoperfusion in 11, basal ganglia hypoperfusion in 9, thalamus and basal ganglia hypoperfusion in 2 and basifrontal hypoperfusion in 1. So far, in ten children with abnormal pretreatment scans, post treatment scans have also been done. In mentat group, 2/5 children showed normalization of perfusion abnormality after treatment whereas in placebo group, 1/5. Conclusion: This study suggests that there is selective focal cerebral hypoperfusion in cases of ADHD and 99mTc-ECD brain SPECT can be used for evaluation and further monitoring of therapeutic outcome in such cases

  17. De novo pathogenic variant in TUBB2A presenting with arthrogryposis multiplex congenita, brain abnormalities, and severe developmental delay.

    Science.gov (United States)

    Ejaz, Resham; Lionel, Anath C; Blaser, Susan; Walker, Susan; Scherer, Stephen W; Babul-Hirji, Riyana; Marshall, Christian R; Stavropoulos, Dimitri J; Chitayat, David

    2017-10-01

    Disorders of brain formation can occur from pathogenic variants in various alpha and beta tubulin genes. Heterozygous pathogenic variants in the beta tubulin isotype A gene, TUBB2A, have been recently implicated in brain malformations, seizures, and developmental delay. Limited information is known regarding the phenotypic spectrum associated with pathogenic variants in this gene given the rarity of the condition. We report the sixth individual with a de novo heterozygous TUBB2A pathogenic variant, who presented with a severe neurological phenotype along with unique features of arthrogryposis multiplex congenita, optic nerve hypoplasia, dysmorphic facial features, and vocal cord paralysis, thereby expanding the gene-related phenotype. © 2017 Wiley Periodicals, Inc.

  18. Swimming attenuates d-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics.

    Science.gov (United States)

    Kou, Xianjuan; Li, Jie; Liu, Xingran; Chang, Jingru; Zhao, Qingxia; Jia, Shaohui; Fan, Jingjing; Chen, Ning

    2017-06-01

    microRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. To explore the regulatory role of miR-34a in aging-related diseases such as Alzheimer's disease (AD) during exercise intervention, we constructed a rat model with d-galactose (d-gal)-induced oxidative stress and cognitive impairment coupled with dysfunctional autophagy and abnormal mitochondrial dynamics, determined the mitigation of cognitive impairment of d-gal-induced aging rats during swimming intervention, and evaluated miR-34a-mediated functional status of autophagy and abnormal mitochondrial dynamics. Meanwhile, whether the upregulation of miR-34a can lead to dysfunctional autophagy and abnormal mitochondrial dynamics was confirmed in human SH-SY5Y cells with silenced miR-34a by the transfection of a miR-34a inhibitor. Results indicated that swimming intervention could significantly attenuate cognitive impairment, prevent the upregulation of miR-34a, mitigate the dysfunctional autophagy, and inhibit the increase of dynamin-related protein 1 (DRP1) in d-gal-induced aging model rats. In contrast, the miR-34a inhibitor in cell model not only attenuated D-gal-induced the impairment of autophagy but also decreased the expression of DRP1 and mitofusin 2 (MFN2). Therefore, swimming training can delay brain aging of d-gal-induced aging rats through attenuating the impairment of miR-34a-mediated autophagy and abnormal mitochondrial dynamics, and miR-34a could be the novel therapeutic target for aging-related diseases such as AD. NEW & NOTEWORTHY In the present study, we have found that the upregulation of miR-34a is the hallmark of aging or aging-related diseases, which can result in dysfunctional autophagy and abnormal mitochondrial dynamics. In contrast, swimming intervention can delay the aging process by rescuing the impaired functional status of autophagy and abnormal mitochondrial dynamics via the suppression of miR-34a. Copyright © 2017 the American Physiological Society.

  19. Cortico-striato-thalamo-cortical circuit abnormalities in obsessive-compulsive disorder: A voxel-based morphometric and fMRI study of the whole brain.

    Science.gov (United States)

    Tang, Wenxin; Zhu, Qifeng; Gong, Xiangyang; Zhu, Cheng; Wang, Yiquan; Chen, Shulin

    2016-10-15

    The primary aim of this study was to identify structural and functional abnormalities in the brains of obsessive-compulsive disorder (OCD) patients. Another aim was to assess the effect of serotonin selective reuptake inhibitors (SSRIs) on brain structure of OCD patients. All subjects underwent brain magnetic resonance imaging (MRI) and resting functional MRI (fMRI). High-resolution three-dimensional images were processed using the voxel-based morphometry (VBM) method. The final analysis included 18 OCD patients and 16 healthy controls. In the OCD patients there was a decrease in gray matter volume in the bilateral cingulate cortex and bilateral striatum. In some cortical structures including the cerebellar anterior lobe, left orbital frontal gyrus, right middle frontal gyrus, left middle temporal gyrus, precentral gyrus, and postcentral gyrus, there was an increase in gray matter volume. On fMRI the OCD patients had overactivation of the right cerebellum and right parietal lobe and reduced activation of the left cingulate gyrus, putamen, and caudate nucleus. Eleven OCD patients who improved during 12 weeks of drug treatment with sertraline hydrochloride had a significant increase in gray matter volume in several brain structures but no significant differences were found on resting fMRI. The results indicated a consistent trend between structural and functional images. Higher cortical structures showed increased gray matter volume and increased activation as did the cerebellum whereas subcortical structures showed decreased gray matter volume and decreased activation. And brain structure improvement consisted with symptom improvement after SSRIs treatment in OCD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose