Brain serotonin content - Increase following ingestion of carbohydrate diet.

Science.gov (United States)

Fernstrom, J. D.; Wurtman, R. J.

1971-01-01

In the rat, the injection of insulin or the consumption of carbohydrate causes sequential increases in the concentrations of tryptophan in the plasma and the brain and of serotonin in the brain. Serotonin-containing neurons may thus participate in systems whereby the rat brain integrates information about the metabolic state in its relation to control of homeostasis and behavior.

Phosphodiesterase type 5 inhibitors increase Herceptin transport and treatment efficacy in mouse metastatic brain tumor models.

Directory of Open Access Journals (Sweden)

Jinwei Hu

2010-04-01

Full Text Available Chemotherapeutic drugs and newly developed therapeutic monoclonal antibodies are adequately delivered to most solid and systemic tumors. However, drug delivery into primary brain tumors and metastases is impeded by the blood-brain tumor barrier (BTB, significantly limiting drug use in brain cancer treatment.We examined the effect of phosphodiesterase 5 (PDE5 inhibitors in nude mice on drug delivery to intracranially implanted human lung and breast tumors as the most common primary tumors forming brain metastases, and studied underlying mechanisms of drug transport. In vitro assays demonstrated that PDE5 inhibitors enhanced the uptake of [(14C]dextran and trastuzumab (Herceptin, a humanized monoclonal antibody against HER2/neu by cultured mouse brain endothelial cells (MBEC. The mechanism of drug delivery was examined using inhibitors for caveolae-mediated endocytosis, macropinocytosis and coated pit/clathrin endocytosis. Inhibitor analysis strongly implicated caveolae and macropinocytosis endocytic pathways involvement in the PDE5 inhibitor-enhanced Herceptin uptake by MBEC. Oral administration of PDE5 inhibitor, vardenafil, to mice with HER2-positive intracranial lung tumors led to an increased tumor permeability to high molecular weight [(14C]dextran (2.6-fold increase and to Herceptin (2-fold increase. Survival time of intracranial lung cancer-bearing mice treated with Herceptin in combination with vardenafil was significantly increased as compared to the untreated, vardenafil- or Herceptin-treated mice (p0.05.These findings suggest that PDE5 inhibitors may effectively modulate BTB permeability, and enhance delivery and therapeutic efficacy of monoclonal antibodies in hard-to-treat brain metastases from different primary tumors that had metastasized to the brain.

Increased brain connectivity and activation after cognitive rehabilitation in Parkinson's disease: a randomized controlled trial.

Science.gov (United States)

Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Lucas-Jiménez, Olaia; Gómez-Esteban, Juan Carlos; Gómez-Beldarrain, Maria Ángeles; Ibarretxe-Bilbao, Naroa

2017-12-01

Cognitive rehabilitation programs have demonstrated efficacy in improving cognitive functions in Parkinson's disease (PD), but little is known about cerebral changes associated with an integrative cognitive rehabilitation in PD. To assess structural and functional cerebral changes in PD patients, after attending a three-month integrative cognitive rehabilitation program (REHACOP). Forty-four PD patients were randomly divided into REHACOP group (cognitive rehabilitation) and a control group (occupational therapy). T1-weighted, diffusion weighted and functional magnetic resonance images (fMRI) during resting-state and during a memory paradigm (with learning and recognition tasks) were acquired at pre-treatment and post-treatment. Cerebral changes were assessed with repeated measures ANOVA 2 × 2 for group x time interaction. During resting-state fMRI, the REHACOP group showed significantly increased brain connectivity between the left inferior temporal lobe and the bilateral dorsolateral prefrontal cortex compared to the control group. Moreover, during the recognition fMRI task, the REHACOP group showed significantly increased brain activation in the left middle temporal area compared to the control group. During the learning fMRI task, the REHACOP group showed increased brain activation in the left inferior frontal lobe at post-treatment compared to pre-treatment. No significant structural changes were found between pre- and post-treatment. Finally, the REHACOP group showed significant and positive correlations between the brain connectivity and activation and the cognitive performance at post-treatment. This randomized controlled trial suggests that an integrative cognitive rehabilitation program can produce significant functional cerebral changes in PD patients and adds evidence to the efficacy of cognitive rehabilitation programs in the therapeutic approach for PD.

Effects of diabetes on brain metabolism - is brain glycogen a significant player?

DEFF Research Database (Denmark)

Sickmann, Helle M; Waagepetersen, Helle S.

2015-01-01

Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose to the br......Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose...... to the brain may be affected and have important impacts on brain metabolism and neurotransmission. This also implies that brain glycogen may serve an essential role in the diabetic state to sustain appropriate brain function. There are two main types of diabetes; type 1 and type 2 diabetes and both types may...... understanding of how brain energy and neurotransmitter metabolism is affected in diabetes. There will be a particular focus on the role of brain glycogen to support glycolytic and TCA cycle activity as well as glutamate-glutamine cycle in type 1 and type 2 diabetes....

Magnesium enhances exercise performance via increasing glucose availability in the blood, muscle, and brain during exercise.

Directory of Open Access Journals (Sweden)

Hsuan-Ying Chen

Full Text Available Glucose mobilization and utilization in the periphery and central nervous system are important during exercise and are responsible for exercise efficacy. Magnesium (Mg is involved in energy production and plays a role in exercise performance. This study aimed to explore the effects of Mg on the dynamic changes in glucose and lactate levels in the muscle, blood and brain of exercising rats using a combination of auto-blood sampling and microdialysis. Sprague-Dawley rats were pretreated with saline or magnesium sulfate (MgSO4, 90 mg/kg, i.p. 30 min before treadmill exercise (20 m/min for 60 min. Our results indicated that the muscle, blood, and brain glucose levels immediately increased during exercise, and then gradually decreased to near basal levels in the recovery periods of both groups. These glucose levels were significantly enhanced to approximately two-fold (P<0.05 in the Mg group. Lactate levels in the muscle, blood, and brain rapidly and significantly increased in both groups during exercise, and brain lactate levels in the Mg group further elevated (P<0.05 than those in the control group during exercise. Lactate levels significantly decreased after exercise in both groups. In conclusion, Mg enhanced glucose availability in the peripheral and central systems, and increased lactate clearance in the muscle during exercise.

Significance of MDR1 and multiple drug resistance in refractory human epileptic brain

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Dini Gabriele

2004-10-01

Full Text Available Abstract Background The multiple drug resistance protein (MDR1/P-glycoprotein is overexpressed in glia and blood-brain barrier (BBB endothelium in drug refractory human epileptic tissue. Since various antiepileptic drugs (AEDs can act as substrates for MDR1, the enhanced expression/function of this protein may increase their active extrusion from the brain, resulting in decreased responsiveness to AEDs. Methods Human drug resistant epileptic brain tissues were collected after surgical resection. Astrocyte cell cultures were established from these tissues, and commercially available normal human astrocytes were used as controls. Uptake of fluorescent doxorubicin and radioactive-labeled Phenytoin was measured in the two cell populations, and the effect of MDR1 blockers was evaluated. Frozen human epileptic brain tissue slices were double immunostained to locate MDR1 in neurons and glia. Other slices were exposed to toxic concentrations of Phenytoin to study cell viability in the presence or absence of a specific MDR1 blocker. Results MDR1 was overexpressed in blood vessels, astrocytes and neurons in human epileptic drug-resistant brain. In addition, MDR1-mediated cellular drug extrusion was increased in human 'epileptic' astrocytes compared to 'normal' ones. Concomitantly, cell viability in the presence of cytotoxic compounds was increased. Conclusions Overexpression of MDR1 in different cell types in drug-resistant epileptic human brain leads to functional alterations, not all of which are linked to drug pharmacokinetics. In particular, the modulation of glioneuronal MDR1 function in epileptic brain in the presence of toxic concentrations of xenobiotics may constitute a novel cytoprotective mechanism.

The Increase of the Functional Entropy of the Human Brain with Age

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Yao, Y.; Lu, W. L.; Xu, B.; Li, C. B.; Lin, C. P.; Waxman, D.; Feng, J. F.

2013-01-01

We use entropy to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. We attribute this to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. Our dataset involved males and females and we found significant differences between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy. PMID:24103922

Increased self-diffusion of brain water in normal aging

DEFF Research Database (Denmark)

Gideon, P; Thomsen, C; Henriksen, O

1994-01-01

With magnetic resonance (MR) imaging, brain water self-diffusion was measured in 17 healthy volunteers 22-76 (mean, 44.6) years old. The calculated values for the apparent diffusion coefficients (ADCs) ranged from 0.58 x 10(-9) to 1.23 x 10(-9) m2/sec in cerebral white matter. A significant...... by an increase in the extracellular volume due to age-dependent neuronal degeneration or to changes in myelination. These findings have implications for future clinical investigations with diffusion MR imaging techniques in patients with neurologic diseases, and stress the importance of having an age...

The biological significance of brain barrier mechanisms

DEFF Research Database (Denmark)

Saunders, Norman R; Habgood, Mark D; Møllgård, Kjeld

2016-01-01

, but more work is required to evaluate the method before it can be tried in patients. Overall, our view is that much more fundamental knowledge of barrier mechanisms and development of new experimental methods will be required before drug targeting to the brain is likely to be a successful endeavor......Barrier mechanisms in the brain are important for its normal functioning and development. Stability of the brain's internal environment, particularly with respect to its ionic composition, is a prerequisite for the fundamental basis of its function, namely transmission of nerve impulses....... In addition, the appropriate and controlled supply of a wide range of nutrients such as glucose, amino acids, monocarboxylates, and vitamins is also essential for normal development and function. These are all cellular functions across the interfaces that separate the brain from the rest of the internal...

Increased power spectral density in resting-state pain-related brain networks in fibromyalgia.

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Kim, Ji-Young; Kim, Seong-Ho; Seo, Jeehye; Kim, Sang-Hyon; Han, Seung Woo; Nam, Eon Jeong; Kim, Seong-Kyu; Lee, Hui Joong; Lee, Seung-Jae; Kim, Yang-Tae; Chang, Yongmin

2013-09-01

Fibromyalgia (FM), characterized by chronic widespread pain, is known to be associated with heightened responses to painful stimuli and atypical resting-state functional connectivity among pain-related regions of the brain. Previous studies of FM using resting-state functional magnetic resonance imaging (rs-fMRI) have focused on intrinsic functional connectivity, which maps the spatial distribution of temporal correlations among spontaneous low-frequency fluctuation in functional MRI (fMRI) resting-state data. In the current study, using rs-fMRI data in the frequency domain, we investigated the possible alteration of power spectral density (PSD) of low-frequency fluctuation in brain regions associated with central pain processing in patients with FM. rsfMRI data were obtained from 19 patients with FM and 20 age-matched healthy female control subjects. For each subject, the PSDs for each brain region identified from functional connectivity maps were computed for the frequency band of 0.01 to 0.25 Hz. For each group, the average PSD was determined for each brain region and a 2-sample t test was performed to determine the difference in power between the 2 groups. According to the results, patients with FM exhibited significantly increased frequency power in the primary somatosensory cortex (S1), supplementary motor area (SMA), dorsolateral prefrontal cortex, and amygdala. In patients with FM, the increase in PSD did not show an association with depression or anxiety. Therefore, our findings of atypical increased frequency power during the resting state in pain-related brain regions may implicate the enhanced resting-state baseline neural activity in several brain regions associated with pain processing in FM. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Enteral nutrition increases interstitial brain glucose levels in poor-grade subarachnoid hemorrhage patients.

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Kofler, Mario; Schiefecker, Alois J; Beer, Ronny; Gaasch, Maxime; Rhomberg, Paul; Stover, John; Pfausler, Bettina; Thomé, Claudius; Schmutzhard, Erich; Helbok, Raimund

2018-03-01

Low brain tissue glucose levels after acute brain injury are associated with poor outcome. Whether enteral nutrition (EN) reliably increases cerebral glucose levels remains unclear. In this retrospective analysis of prospectively collected observational data, we investigate the effect of EN on brain metabolism in 17 poor-grade subarachnoid hemorrhage (SAH) patients undergoing cerebral microdialysis (CMD) monitoring. CMD-values were obtained hourly. A nutritional intervention was defined as the clinical routine administration of EN without supplemental parenteral nutrition. Sixty-three interventions were analyzed. The mean amount of EN per intervention was 472.4 ± 10.7 kcal. CMD-glucose levels significantly increased from 1.59 ± 0.13 mmol/l at baseline to a maximum of 2.03 ± 0.2 mmol/l after 5 h (p  40) and the microdialysis probe location. The increase in CMD-glucose was directly dependent on the magnitude of increase of serum glucose levels (p = 0.007). No change in CMD-lactate, CMD-pyruvate, CMD-LPR, or CMD-glutamate (p > 0.4) was observed. Routine EN also increased CMD-glucose even if baseline concentrations were critically low ( < 0.7 mmol/l, neuroglucopenia; p < 0.001). These results may have treatment implications regarding glucose management of poor-grade aneurysmal SAH patients.

Repairing the brain with physical exercise: Cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention

Directory of Open Access Journals (Sweden)

Kamila U. Szulc-Lerch

Full Text Available There is growing evidence that exercise induced experience dependent plasticity may foster structural and functional recovery following brain injury. We examined the efficacy of exercise training for neural and cognitive recovery in long-term pediatric brain tumor survivors treated with radiation.We conducted a controlled clinical trial with crossover of exercise training (vs. no training in a volunteer sample of 28 children treated with cranial radiation for brain tumors (mean age = 11.5 yrs.; mean time since diagnosis = 5.7 yrs. The endpoints were anatomical T1 MRI data and multiple behavioral outcomes presenting a broader analysis of structural MRI data across the entire brain. This included an analysis of changes in cortical thickness and brain volume using automated, user unbiased approaches. A series of general linear mixed effects models evaluating the effects of exercise training on cortical thickness were performed in a voxel and vertex-wise manner, as well as for specific regions of interest. In exploratory analyses, we evaluated the relationship between changes in cortical thickness after exercise with multiple behavioral outcomes, as well as the relation of these measures at baseline.Exercise was associated with increases in cortical thickness within the right pre and postcentral gyri. Other notable areas of increased thickness related to training were present in the left pre and postcentral gyri, left temporal pole, left superior temporal gyrus, and left parahippocampal gyrus. Further, we observed that compared to a separate cohort of healthy children, participants displayed multiple areas with a significantly thinner cortex prior to training and fewer differences following training, indicating amelioration of anatomical deficits. Partial least squares analysis (PLS revealed specific patterns of relations between cortical thickness and various behavioral outcomes both after training and at baseline.Overall, our results

Dietary guanidinoacetic acid increases brain creatine levels in healthy men

DEFF Research Database (Denmark)

Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik

2017-01-01

OBJECTIVE: Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA......, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity. RESULTS: Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation......, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8...

Increased blood-brain transfer in a rabbit model of acute liver failure

International Nuclear Information System (INIS)

Horowitz, M.E.; Schafer, D.F.; Molnar, P.; Jones, E.A.; Blasberg, R.G.; Patlak, C.S.; Waggoner, J.; Fenstermacher, J.D.

1983-01-01

The blood-to-brain transfer of [ 14 C]alpha-aminoisobutyric acid was investigated by quantitative autoradiography in normal rabbits and rabbits with acute liver failure induced by the selective hepatotoxin galactosamine. The blood-to-brain transfer of alpha-aminoisobutyric acid was similar in control animals and animals 2 and 7 h after galactosamine injections, but was increased five- to tenfold in certain gray-matter areas of the brain in animals 11 and 18 h after galactosamine treatment. No detectable differences in white-matter uptake of [ 14 C]alpha-aminoisobutyric acid were found between the control and treated groups. The increase in alpha-aminoisobutyric acid transfer within the gray-matter areas suggested that a general or nonspecific increase in brain capillary permeability occurred in these areas. No clinical signs of early hepatic encephalopathy were observed in the treated rabbits, except for 1 animal from the 18-h postgalactosamine group. Thus, enhanced blood-brain transfer of alpha-aminoisobutyric acid preceded the development of overt hepatic encephalopathy. The distribution of radioactivity after the intravenous administration of [ 14 C]galactosamine showed that virtually none of the hepatotoxin localized in the brain, suggesting that the drug itself does not have a direct effect upon the blood-brain barrier or the brain. The increased uptake of alpha-aminoisobutyric acid at 11 and 18 h implies that the transfer of other solutes would also be enhanced, that central nervous system homeostasis would be compromised, and that the resulting changes in brain fluid composition could contribute to or cause hepatic encephalopathy

Repeated mild traumatic brain injury in female rats increases lipid peroxidation in neurons.

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Yates, Nathanael J; Lydiard, Stephen; Fehily, Brooke; Weir, Gillian; Chin, Aaron; Bartlett, Carole A; Alderson, Jacqueline; Fitzgerald, Melinda

2017-07-01

Negative outcomes of mild traumatic brain injury (mTBI) can be exacerbated by repeated insult. Animal models of repeated closed-head mTBI provide the opportunity to define acute pathological mechanisms as the number of mTBI increases. Furthermore, little is known about the effects of mTBI impact site, and how this may affect brain function. We use a closed head, weight drop model of mTBI that allows head movement following impact, in adult female rats to determine the role of the number and location of mTBI on brain pathology and behaviour. Biomechanical assessment of two anatomically well-defined mTBI impact sites were used, anterior (bregma) and posterior (lambda). Location of the impact had no significant effect on impact forces (450 N), and the weight impact locations were on average 5.4 mm from the desired impact site. No between location vertical linear head kinematic differences were observed immediately following impact, however, in the 300 ms post-impact, significantly higher mean vertical head displacement and velocity were observed in the mTBI lambda trials. Breaches of the blood brain barrier were observed with three mTBI over bregma, associated with immunohistochemical indicators of damage. However, an increased incidence of hairline fractures of the skull and macroscopic haemorrhaging made bregma an unsuitable impact location to model repeated mTBI. Repeated mTBI over lambda did not cause skull fractures and were examined more comprehensively, with outcomes following one, two or three mTBI or sham, delivered at 1 day intervals, assessed on days 1-4. We observe a mild behavioural phenotype, with subtle deficits in cognitive function, associated with no identifiable neuroanatomical or inflammatory changes. However, an increase in lipid peroxidation in a subset of cortical neurons following two mTBI indicates increasing oxidative damage with repeated injury in female rats, supported by increased amyloid precursor protein immunoreactivity with three m

The significance of morphological changes in the brain-tumor interface for the pathogenesis of brain edema in meningioma: Magnetic resonance tomography and intraoperative findings

International Nuclear Information System (INIS)

Bitzer, M.; Klose, U.; Naegele, T.; Mundinger, P.; Voigt, K.; Freudenstein, D.; Heiss, E.

1999-01-01

Purpose: The aim of the study was to verify a possible correlation between macroscopic changes of the brain-tumor interface (BTI) and the development of a peritumoral brain edema in meningiomas. Methods: 27 meningiomas were investigated in this prospective study using an optimized inversion-recovery (IR) sequence. After i.v. administration of 0.2 mmol Gd-DTPA/kg axial and coronary images were acquired (slice thickness=2 mm). The distances of signal altered cortex and obliterations of the subarachnoid space (SAS) were measured at the BTI and related to the pial tumor circumference (cortical-index and SAS-index). Intraoperatively the BTI was divided into the following categories: 0: SAS not obliterated, 1: SAS partially obliterated, 2: Direct contact between tumor and white matter, 3: Tumor infiltration into brain. Results: Edema-associated meningiomas showed a significantly (p=0.0001) increased SAS-index (0.47 vs. 0.07) and cortical index (0.45 vs. 0.0) compared to cases without edema. Intraoperatively 95% of meningiomas with brain edema showed SAS-obliterations, compared to 50% of cases without an edema. Conclusions: Arachnoid adhesions at the BTI with obliteration of the SAS seem to play an essential role in the induction of brain edema in meningiomas. (orig.) [de

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

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Haldar, Swati; Tripathi, Ajai K.; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K.; Singh, Ajay

2014-01-01

Abstract Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders. Antioxid. Redox Signal. 20, 1324–1363. PMID:23815406

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

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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. Copyright © 2017 Endocrine Society

A mutation in the HFE gene is associated with altered brain iron profiles and increased oxidative stress in mice.

Science.gov (United States)

Nandar, Wint; Neely, Elizabeth B; Unger, Erica; Connor, James R

2013-06-01

Because of the increasing evidence that H63D HFE polymorphism appears in higher frequency in neurodegenerative diseases, we evaluated the neurological consequences of H63D HFE in vivo using mice that carry H67D HFE (homologous to human H63D). Although total brain iron concentration did not change significantly in the H67D mice, brain iron management proteins expressions were altered significantly. The 6-month-old H67D mice had increased HFE and H-ferritin expression. At 12 months, H67D mice had increased H- and L-ferritin but decreased transferrin expression suggesting increased iron storage and decreased iron mobilization. Increased L-ferritin positive microglia in H67D mice suggests that microglia increase iron storage to maintain brain iron homeostasis. The 6-month-old H67D mice had increased levels of GFAP, increased oxidatively modified protein levels, and increased cystine/glutamate antiporter (xCT) and hemeoxygenase-1 (HO-1) expression indicating increased metabolic and oxidative stress. By 12 months, there was no longer increased astrogliosis or oxidative stress. The decrease in oxidative stress at 12 months could be related to an adaptive response by nuclear factor E2-related factor 2 (Nrf2) that regulates antioxidant enzymes expression and is increased in the H67D mice. These findings demonstrate that the H63D HFE impacts brain iron homeostasis, and promotes an environment of oxidative stress and induction of adaptive mechanisms. These data, along with literature reports on humans with HFE mutations provide the evidence to overturn the traditional paradigm that the brain is protected from HFE mutations. The H67D knock-in mouse can be used as a model to evaluate how the H63D HFE mutation contributes to neurodegenerative diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

Increased Global Interaction Across Functional Brain Modules During Cognitive Emotion Regulation.

Science.gov (United States)

Brandl, Felix; Mulej Bratec, Satja; Xie, Xiyao; Wohlschläger, Afra M; Riedl, Valentin; Meng, Chun; Sorg, Christian

2017-07-13

Cognitive emotion regulation (CER) enables humans to flexibly modulate their emotions. While local theories of CER neurobiology suggest interactions between specialized local brain circuits underlying CER, e.g., in subparts of amygdala and medial prefrontal cortices (mPFC), global theories hypothesize global interaction increases among larger functional brain modules comprising local circuits. We tested the global CER hypothesis using graph-based whole-brain network analysis of functional MRI data during aversive emotional processing with and without CER. During CER, global between-module interaction across stable functional network modules increased. Global interaction increase was particularly driven by subregions of amygdala and cuneus-nodes of highest nodal participation-that overlapped with CER-specific local activations, and by mPFC and posterior cingulate as relevant connector hubs. Results provide evidence for the global nature of human CER, complementing functional specialization of embedded local brain circuits during successful CER. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Fabp1 gene ablation inhibits high-fat diet-induced increase in brain endocannabinoids.

Science.gov (United States)

Martin, Gregory G; Landrock, Danilo; Chung, Sarah; Dangott, Lawrence J; Seeger, Drew R; Murphy, Eric J; Golovko, Mikhail Y; Kier, Ann B; Schroeder, Friedhelm

2017-01-01

The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside the central nervous system that may mediate the effect of high-fat diet (HFD) on brain endocannabinoid levels. One candidate is the liver fatty acid binding protein (FABP1), a cytosolic protein highly prevalent in liver, but not detected in brain, which facilitates hepatic clearance of fatty acids. The impact of Fabp1 gene ablation (LKO) on the effect of high-fat diet (HFD) on brain and plasma endocannabinoid levels was examined and data expressed for each parameter as the ratio of high-fat diet/control diet. In male wild-type mice, HFD markedly increased brain N-acylethanolamides, but not 2-monoacylglycerols. LKO blocked these effects of HFD in male mice. In female wild-type mice, HFD slightly decreased or did not alter these endocannabinoids as compared with male wild type. LKO did not block the HFD effects in female mice. The HFD-induced increase in brain arachidonic acid-derived arachidonoylethanolamide in males correlated with increased brain-free and total arachidonic acid. The ability of LKO to block the HFD-induced increase in brain arachidonoylethanolamide correlated with reduced ability of HFD to increase brain-free and total arachidonic acid in males. In females, brain-free and total arachidonic acid levels were much less affected by either HFD or LKO in the context of HFD. These data showed that LKO markedly diminished the impact of HFD on brain endocannabinoid levels, especially in male mice. © 2016 International Society for Neurochemistry.

Repairing the brain with physical exercise: Cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention.

Science.gov (United States)

Szulc-Lerch, Kamila U; Timmons, Brian W; Bouffet, Eric; Laughlin, Suzanne; de Medeiros, Cynthia B; Skocic, Jovanka; Lerch, Jason P; Mabbott, Donald J

2018-01-01

There is growing evidence that exercise induced experience dependent plasticity may foster structural and functional recovery following brain injury. We examined the efficacy of exercise training for neural and cognitive recovery in long-term pediatric brain tumor survivors treated with radiation. We conducted a controlled clinical trial with crossover of exercise training (vs. no training) in a volunteer sample of 28 children treated with cranial radiation for brain tumors (mean age = 11.5 yrs.; mean time since diagnosis = 5.7 yrs). The endpoints were anatomical T1 MRI data and multiple behavioral outcomes presenting a broader analysis of structural MRI data across the entire brain. This included an analysis of changes in cortical thickness and brain volume using automated, user unbiased approaches. A series of general linear mixed effects models evaluating the effects of exercise training on cortical thickness were performed in a voxel and vertex-wise manner, as well as for specific regions of interest. In exploratory analyses, we evaluated the relationship between changes in cortical thickness after exercise with multiple behavioral outcomes, as well as the relation of these measures at baseline. Exercise was associated with increases in cortical thickness within the right pre and postcentral gyri. Other notable areas of increased thickness related to training were present in the left pre and postcentral gyri, left temporal pole, left superior temporal gyrus, and left parahippocampal gyrus. Further, we observed that compared to a separate cohort of healthy children, participants displayed multiple areas with a significantly thinner cortex prior to training and fewer differences following training, indicating amelioration of anatomical deficits. Partial least squares analysis (PLS) revealed specific patterns of relations between cortical thickness and various behavioral outcomes both after training and at baseline. Overall, our results indicate that

The significance of faint visualization of the superior sagittal sinus in brain scintigraphy for the diagnosis of brain death

International Nuclear Information System (INIS)

Bisset, R.; Sfakianakis, G.; Ihmedian, I.; Holzman, B.; Curless, R.; Serafini, A.

1985-01-01

Brain death is associated with cessation of blood flow to the brain. Tc-99m brain flow studies are used as a laboratory confirmatory test for the establishment of the diagnosis of brain death. Criteria for the diagnosis of cessation of blood flow to the brain are 1) visualization of carotid artery activity in the neck of the patient and 2) no visualization of activity in the distribution of the anterior and middle cerebral arteries. The authors noticed that in a significant number of patients, although there was no visualization of arterial blood flow to the brain the static images demonstrated faint accumulation of activity in the region of the superior sagittal sinus (SSS). In a four year period 212 brain flow studies were performed in 154 patients for diagnosis of brain death; of them 137 studies (65%) showed no evidence of arterial flow. In 103 out of the 137 studies (75%) there was no visualization of the SSS; in the remaining 34 studies (3l patients) however three patterns of faint activity attributed to partial and or faint visualization of the SSS could be recognized at the midline of the immediate anterior static view: a) linear from the cranial vault floor up b) disk shaped at the apex of the vault and c) disk shaped at the apex tailing caudad. All of the 3l patients in this group satisfied brain death criteria within four days of the last study which showed faint visualization of the superior sagittal sinus. The authors conclude that even in the presence of a faint visualization of the superior sagittal sinus on static post brain flow scintigraphy, the diagnosis of cessation of blood flow to the brain can be made if there is no evidence of arterial blood flow

Radionuclide determination of brain blood flow time and its clinical significance

International Nuclear Information System (INIS)

Vlakhov, N.; Vylkanov, P.; Kirkov, M.

1986-01-01

Brain blood flow time in the two cerebral hemispheres was measured by the method of radioisotope circulography. The radiopharmaceutical used was 131 I-hypuran with activity 3,7 μBq in volume 0,3 ml. Registrations were made with two-channel radiograph GAMMA (Hungary) with external diameter of the colimator 50 mm. Tape speed was 160 mm/min at time costant 10. Patients with neurological and neurosurgical symptoms, as well as a group of normal subjects, were examined. Brain blood flow time varied within the range 5,5-7,5 s for either sex. It was increased in patients with concussion of the brain, epilepsy, atherosclerosis and tumors and shortened in patients with arterio-venous aneurysm. Conclusion is made that the diagnosis value of the method is high, it is practicable with no radiation load and furnisches reliable information on the effectiveness of surgical or drug treatment

Melatonin Secretion Is Increased in Children with Severe Traumatic Brain Injury.

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Marseglia, Lucia; D'Angelo, Gabriella; Manti, Sara; Rulli, Immacolata; Salvo, Vincenzo; Buonocore, Giuseppe; Reiter, Russel J; Gitto, Eloisa

2017-05-13

Traumatic brain injury (TBI) is a leading cause of death and disability in children. Oxidative stress plays a significant role in brain damage and melatonin exhibits both direct and indirect antioxidant effects. The primary aim of the present study was to evaluate serum melatonin levels in children with severe TBI in comparison to critically ill children admitted to the Pediatric Intensive Care Unit for conditions other than TBI. Twenty-four children were evaluated, equally divided into severe TBI and no-TBI. Blood samples for serum melatonin analysis were collected at 22:00, 01:00, 03:00, 05:00, 08:00, and 12:00. Mean serum melatonin peaks in children of the TBI group were higher compared to the values of no-TBI critically ill children (495 ± 102 vs. 294 ± 119 pg/mL, p = 0.0002). Furthermore, the difference was even more significant in comparison to values reported in literature for healthy age-matched children (495 ± 102 vs. 197 ± 71 pg/mL, p melatonin levels dramatically increase in children after severe TBI. This elevation is likely to represent a response to oxidative stress and/or inflammation due to severe head injury.

Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke.

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Zahra Hassani

Full Text Available Stem cell transplantation is to date one of the most promising therapies for chronic ischemic stroke. The human conditionally immortalised neural stem cell line, CTX0E03, has demonstrable efficacy in a rodent model of stroke and is currently in clinical trials. Nonetheless, the mechanisms by which it promotes brain repair are not fully characterised. This study investigated the cellular events occurring after CTX0E03 transplantation in the brains of rats that underwent ischemic stroke.We focused on the endogenous proliferative activity of the host brain in response to cell transplantation and determined the identity of the proliferating cells using markers for young neurons (doublecortin, Dcx and microglia (CD11b. So as to determine the chronology of events occurring post-transplantation, we analysed the engrafted brains one week and four weeks post-transplantation.We observed a significantly greater endogenous proliferation in the striatum of ischemic brains receiving a CTX0E03 graft compared to vehicle-treated ischemic brains. A significant proportion of these proliferative cells were found to be Dcx+ striatal neuroblasts. Further, we describe an enhanced immune response after CTX0E03 engraftment, as shown by a significant increase of proliferating CD11b+ microglial cells.Our study demonstrates that few Dcx+ neuroblasts are proliferative in normal conditions, and that this population of proliferative neuroblasts is increased in response to stroke. We further show that CTX0E03 transplantation after stroke leads to the maintenance of this proliferative activity. Interestingly, the preservation of neuronal proliferative activity upon CTX0E03 transplantation is preceded and accompanied by a high rate of proliferating microglia. Our study suggests that microglia might mediate in part the effect of CTX0E03 transplantation on neuronal proliferation in ischemic stroke conditions.

Magnetic susceptibility artifacts in a diffuse brain injury and their pathological significance

International Nuclear Information System (INIS)

Taguchi, Yoshio; Miyakita, Yasuji; Matsuzawa, Motoshi; Sakakibara, Yohtaro; Takahara, Taro; Yamaguchi, Toshio

1998-01-01

In our study, FLAIR images and multishot echo planar imaging T2-weighted images (EPI T2-WI) were used in addition to conventional T1-weighted images, T2-weighted images and T2-weighted sagittal images. In this series we focused our attention on small parenchymatous lesions of a mild or moderate form of diffuse brain injury. These injuries are shown as high intensity areas on T2-weighted images (T2-high intensity lesions) but are not visualized in CT images. This series consisted of 29 patients who were diagnosed with diffuse brain injury and whose CT scans showed a Diffuse Injury I or II. Nineteen patients were studied in an acute or subacute stage. In all but 3 patients, small T2-high intensity lesions were found in the brain parenchyma. In the follow-up study brain edema was suggested because the lesions tended to be absent within 3 months in T2-weighted images and FLAIR. In 10 patients examined during a chronic stage. Small hemorrhages in patients with Diffuse Injury II were shown with variable intensities on the conventional T1- and T2-weighted images, but were visualized with low intensity in an EPI T2-WI. In diffuse brain injuries, small T2-high intensity lesions have been considered to be brain edema or ischemic insults. Our data however, suggested that microhemorrhages associated with brain edema were resent in most of the supratentorial lesions, and in more than a half of the lesions in the corpus callosum and the brain stem. These findings appear similar to contusions, which are defined as traumatic bruises of the neural parenchyma. The use of MRI has increased our understanding of in vivo pathological changes in mild or moderate forms of diffuse brain injury. (K.H.)

Dietary Tocotrienol/γ-Cyclodextrin Complex Increases Mitochondrial Membrane Potential and ATP Concentrations in the Brains of Aged Mice

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Anke Schloesser

2015-01-01

Full Text Available Brain aging is accompanied by a decrease in mitochondrial function. In vitro studies suggest that tocotrienols, including γ- and δ-tocotrienol (T3, may exhibit neuroprotective properties. However, little is known about the effect of dietary T3 on mitochondrial function in vivo. In this study, we monitored the effect of a dietary T3/γ-cyclodextrin complex (T3CD on mitochondrial membrane potential and ATP levels in the brain of 21-month-old mice. Mice were fed either a control diet or a diet enriched with T3CD providing 100 mg T3 per kg diet for 6 months. Dietary T3CD significantly increased mitochondrial membrane potential and ATP levels compared to those of controls. The increase in MMP and ATP due to dietary T3CD was accompanied by an increase in the protein levels of the mitochondrial transcription factor A (TFAM. Furthermore, dietary T3CD slightly increased the mRNA levels of superoxide dismutase, γ-glutamyl cysteinyl synthetase, and heme oxygenase 1 in the brain. Overall, the present data suggest that T3CD increases TFAM, mitochondrial membrane potential, and ATP synthesis in the brains of aged mice.

Prognostic significance of blood-brain barrier disruption in patients with severe nonpenetrating traumatic brain injury requiring decompressive craniectomy.

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Ho, Kwok M; Honeybul, Stephen; Yip, Cheng B; Silbert, Benjamin I

2014-09-01

The authors assessed the risk factors and outcomes associated with blood-brain barrier (BBB) disruption in patients with severe, nonpenetrating, traumatic brain injury (TBI) requiring decompressive craniectomy. At 2 major neurotrauma centers in Western Australia, a retrospective cohort study was conducted among 97 adult neurotrauma patients who required an external ventricular drain (EVD) and decompressive craniectomy during 2004-2012. Glasgow Outcome Scale scores were used to assess neurological outcomes. Logistic regression was used to identify factors associated with BBB disruption, defined by a ratio of total CSF protein concentrations to total plasma protein concentration > 0.007 in the earliest CSF specimen collected after TBI. Of the 252 patients who required decompressive craniectomy, 97 (39%) required an EVD to control intracranial pressure, and biochemical evidence of BBB disruption was observed in 43 (44%). Presence of disruption was associated with more severe TBI (median predicted risk for unfavorable outcome 75% vs 63%, respectively; p = 0.001) and with worse outcomes at 6, 12, and 18 months than was absence of BBB disruption (72% vs 37% unfavorable outcomes, respectively; p = 0.015). The only risk factor significantly associated with increased risk for BBB disruption was presence of nonevacuated intracerebral hematoma (> 1 cm diameter) (OR 3.03, 95% CI 1.23-7.50; p = 0.016). Although BBB disruption was associated with more severe TBI and worse long-term outcomes, when combined with the prognostic information contained in the Corticosteroid Randomization after Significant Head Injury (CRASH) prognostic model, it did not seem to add significant prognostic value (area under the receiver operating characteristic curve 0.855 vs 0.864, respectively; p = 0.453). Biochemical evidence of BBB disruption after severe nonpenetrating TBI was common, especially among patients with large intracerebral hematomas. Disruption of the BBB was associated with more severe

Increased toll-like receptor 4 in cerebral endothelial cells contributes to the astrocyte swelling and brain edema in acute hepatic encephalopathy.

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Jayakumar, Arumugam R; Tong, Xiao Y; Curtis, Kevin M; Ruiz-Cordero, Roberto; Abreu, Maria T; Norenberg, Michael D

2014-03-01

Astrocyte swelling and the subsequent increase in intracranial pressure and brain herniation are major clinical consequences in patients with acute hepatic encephalopathy. We recently reported that conditioned media from brain endothelial cells (ECs) exposed to ammonia, a mixture of cytokines (CKs) or lipopolysaccharide (LPS), when added to astrocytes caused cell swelling. In this study, we investigated the possibility that ammonia and inflammatory agents activate the toll-like receptor 4 (TLR4) in ECs, resulting in the release of factors that ultimately cause astrocyte swelling. We found a significant increase in TLR4 protein expression when ECs were exposed to ammonia, CKs or LPS alone, while exposure of ECs to a combination of these agents potentiate such effects. In addition, astrocytes exposed to conditioned media from TLR4-silenced ECs that were treated with ammonia, CKs or LPS, resulted in a significant reduction in astrocyte swelling. TLR4 protein up-regulation was also detected in rat brain ECs after treatment with the liver toxin thioacetamide, and that thioacetamide-treated TLR4 knock-out mice exhibited a reduction in brain edema. These studies strongly suggest that ECs significantly contribute to the astrocyte swelling/brain edema in acute hepatic encephalopathy, likely as a consequence of increased TLR4 protein expression by blood-borne noxious agents. © 2013 International Society for Neurochemistry.

Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein

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Lee, Anna M; Miksys, Sharon; Tyndale, Rachel F

2006-01-01

CYP2B6 is a drug-metabolizing enzyme expressed in the liver and brain that can metabolize bupropion (Zyban®, a smoking cessation drug), activate tobacco-smoke nitrosamines, and inactivate nicotine. Hepatic CYP2B6 is induced by phenobarbital and induction may affect in vivo nicotine disposition, while brain CYP2B6 induction may affect local levels of centrally acting substrates. We investigated the effect of chronic phenobarbital treatment on induction of in vivo nicotine disposition and CYP2B6 expression in the liver and brain of African Green (Vervet) monkeys. Monkeys were split into two groups (n=6 each) and given oral saccharin daily for 22 days; one group was supplemented with 20 mg kg−1 phenobarbital. Monkeys were given a 0.1 mg kg−1 nicotine dose subcutaneously before and after treatment. Phenobarbital treatment resulted in a significant, 56%, decrease (P=0.04) in the maximum nicotine plasma concentration and a 46% decrease (P=0.003) in the area under the concentration–time curve. Phenobarbital also increased hepatic CYP2B6 protein expression. In monkey brain, significant induction (Pphenobarbital treatment in monkeys resulted in increased in vivo nicotine disposition, and induced hepatic and brain CYP2B6 protein levels and cellular expression. This induction may alter the metabolism of CYP2B6 substrates including peripherally acting drugs such as cyclophosphamide and centrally acting drugs such as bupropion, ecstasy and phencyclidine. PMID:16751792

Clinical Significance of Brain SPECT in Zipeprol Abusers

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Cho, Dai Ok; Kim, Jae Phil; Kim, Deog Yoon; Yang, Hyung In; Koh, Eun Mi; Kim, Kwang Won; Choi, Young Kil [Kyung Hee University College of Medicine, Seoul (Korea, Republic of)

1993-03-15

Drug abuse is widespread in worldwide and has been associated with neurologic complication. Zipeprol is one of drugs which been abused for psychological satisfaction in some adolescents. This agent is non-opioid antitussive agent, which is not legally considered as being capable of creating dependence or abuse liability at therapeutic serum levels. But it has been reported that acute or chronic overdose create neurologic complication such as convulsion as well as dependence. Recently we experienced six zipeprol abusers who admitted due to convulsion and variable neurologic symptoms. The aim of our study was to determine the role of Tc-99m- HMPAO brain SPECT in those patients. EEG and brain CT showed no abnormal finding, but brain SPECT showed focal or multiple perfusion abnormalities in frontal, parietal, occipital cortex, basal ganglia, thalamus and especially at temporal cortex. These results suggest that brain SPECT may be a useful diagnostic tool to evaluate the cerebral dysfunction induced by zipeprol abuse.

Clinical Significance of Brain SPECT in Zipeprol Abusers

International Nuclear Information System (INIS)

Cho, Dai Ok; Kim, Jae Phil; Kim, Deog Yoon; Yang, Hyung In; Koh, Eun Mi; Kim, Kwang Won; Choi, Young Kil

1993-01-01

Drug abuse is widespread in worldwide and has been associated with neurologic complication. Zipeprol is one of drugs which been abused for psychological satisfaction in some adolescents. This agent is non-opioid antitussive agent, which is not legally considered as being capable of creating dependence or abuse liability at therapeutic serum levels. But it has been reported that acute or chronic overdose create neurologic complication such as convulsion as well as dependence. Recently we experienced six zipeprol abusers who admitted due to convulsion and variable neurologic symptoms. The aim of our study was to determine the role of Tc-99m- HMPAO brain SPECT in those patients. EEG and brain CT showed no abnormal finding, but brain SPECT showed focal or multiple perfusion abnormalities in frontal, parietal, occipital cortex, basal ganglia, thalamus and especially at temporal cortex. These results suggest that brain SPECT may be a useful diagnostic tool to evaluate the cerebral dysfunction induced by zipeprol abuse.

Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions

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Benedito M.A.C.

2001-01-01

Full Text Available Some upper brainstem cholinergic neurons (pedunculopontine and laterodorsal tegmental nuclei are involved in the generation of rapid eye movement (REM sleep and project rostrally to the thalamus and caudally to the medulla oblongata. A previous report showed that 96 h of REM sleep deprivation in rats induced an increase in the activity of brainstem acetylcholinesterase (Achase, the enzyme which inactivates acetylcholine (Ach in the synaptic cleft. There was no change in the enzyme's activity in the whole brain and cerebrum. The components of the cholinergic synaptic endings (for example, Achase are not uniformly distributed throughout the discrete regions of the brain. In order to detect possible regional changes we measured Achase activity in several discrete rat brain regions (medulla oblongata, pons, thalamus, striatum, hippocampus and cerebral cortex after 96 h of REM sleep deprivation. Naive adult male Wistar rats were deprived of REM sleep using the flower-pot technique, while control rats were left in their home cages. Total, membrane-bound and soluble Achase activities (nmol of thiocholine formed min-1 mg protein-1 were assayed photometrically. The results (mean ± SD obtained showed a statistically significant (Student t-test increase in total Achase activity in the pons (control: 147.8 ± 12.8, REM sleep-deprived: 169.3 ± 17.4, N = 6 for both groups, P<0.025 and thalamus (control: 167.4 ± 29.0, REM sleep-deprived: 191.9 ± 15.4, N = 6 for both groups, P<0.05. Increases in membrane-bound Achase activity in the pons (control: 171.0 ± 14.7, REM sleep-deprived: 189.5 ± 19.5, N = 6 for both groups, P<0.05 and soluble enzyme activity in the medulla oblongata (control: 147.6 ± 16.3, REM sleep-deprived: 163.8 ± 8.3, N = 6 for both groups, P<0.05 were also observed. There were no statistically significant differences in the enzyme's activity in the other brain regions assayed. The present findings show that the increase in Achase activity

Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats.

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Tong, Wenni; Chen, Wanqiu; Ostrowski, Robert P; Ma, Qingyi; Souvenir, Rhonda; Zhang, Lubo; Zhang, John H; Tang, Jiping

2010-02-15

A recent study has shown that increased activity of matrix metalloproteinases-2 and metalloproteinases-9 (MMP-2 and MMP-9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP-2 and MMP-9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP-2 and MMP-9 and the protein abundance of TIMP-1 and TIMP-2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP-2 at day 0, and increased MMP-9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP-2, MMP-9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals.

[3H]muscimol binding sites increased in autopsied brains of chronic schizophrenics

International Nuclear Information System (INIS)

Hanada, S.; Mita, T.; Nishino, N.; Tanaka, C.

1987-01-01

[ 3 H]muscimol binding and glutamic acid decarboxylase (GAD) activity in the prefrontal cortex and caudate nucleus of autopsied brains from 19 chronic schizophrenics and 17 control subjects were investigated. In the schizophrenics, saturation analysis with varying concentrations of [ 3 H]muscimol revealed an increase in the number GABA/sub A/ receptors, but there was no significant difference in the affinity. In addition, the enhancement of [ 3 H]muscimol binding by diazepam was significantly greater in schizophrenics than in controls. GAD activity did not differ between controls and schizophrenics. The possibility that GABAergic mechanisms might play a role in case of chronic schizophrenia should be given further attention

Significance of parietal projection in radiosotope scintigraphy of the brain

International Nuclear Information System (INIS)

Fomchenkov, E.P.

1978-01-01

The diagnostic value of the isotope scintigraphy of the brain in the parieal projection with the change of the dip angle of the gamma-chamber detector to the plane of the physiological horizontal was revealed. The observation was made on 100 patients with suspected presence of the volumetric process of the brain. Three variants of placing were studied: the parietal projection - standard (collimator plane parallel to the plane of physiological horizontal and strictly perpendicular to the sagittal plane); the placing with an angle of 30 deg between the detector plane and the physiological horizontal, opened at the front (posterio-parietal); placing with an angle of 30 deg between the detector plane and the physiological horizontal opened at the back (anterio-parietal). A comparative analysis of scintigrams with focal processes of the brain showed the largest informativeness of the proposed modification of the parietal projection in the form of a change of the dip angle of the gamma-chamber detector plane to the plane of the physiological horizontal opened at the back; this makes it possible to reveal more thoroughly the focus of the increased, pathological accumulation of the isotope in different parts of the skull, where the use of as standard placing is of small informativeness

Increased 5-hydroxymethylation levels in the sub ventricular zone of the Alzheimer's brain

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Diego Mastroeni

2016-06-01

Full Text Available The subventricular zone (SVZ is a site of neurogenesis in the aging brain, and epigenetic mechanisms have been implicated in regulating the “normal” distribution of new nerve cells into the existing cellular milieu. In a case-control study of human primary SVZ cultures and fixed tissue from the same individuals, we have found significant increases in DNA hydroxymethylation levels in the SVZ of Alzheimer's disease patients compared with nondiseased control subjects. We show that this increase in hydroxymethylation directly correlates to an increase in cellular proliferation in Alzheimer's disease precursor cells, which implicates the hydroxymethylation tag to a higher degree of cellular proliferation.

The Significance of Brain Transcranial Sonography in Burning Mouth Syndrome: a Pilot Study

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Iris Zavoreo

2017-01-01

Full Text Available Objective: Burning mouth syndrome (BMS is a chronic disorder which is affecting mostly postmenopausal women and is characterized by burning symptoms in the oral cavity on the clinically healthy oral mucosa. The results of previous studies suggested a possible role of peripheral and/or central neurological disturbances in these patients. The aim of this study was to analyze patients with burning mouth syndrome using transcranial sonography. Methods: By use of transcranial sonography of the brain parenchyma, substantia nigra, midbrain raphe and brain nucleus were evaluated in 20 patients with BMS (64.7±12.3 years and 20 controls with chronic pain in the lumbosacral region (61.5±15. Statistical analysis was performed by use of Student t test with significance set at p<0.05. Results: The results of this study have shown hypoechogenicity of the substantia nigra and midbrain raphe as well as hyperechogenicity of the brain nucleus in BMS patients (p<0,05 as compared to controls. Conclusions: Altered transcranial sonography findings of the brain parenchyma, midbrain raphe and brain nucleus in patients with burning mouth syndrome might reflect central disturbances within this syndrome.

Brain catalase activity inhibition as well as opioid receptor antagonism increases ethanol-induced HPA axis activation.

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Pastor, Raúl; Sanchis-Segura, Carles; Aragon, Carlos M G

2004-12-01

Growing evidence indicates that brain catalase activity is involved in the psychopharmacological actions of ethanol. Recent data suggest that participation of this enzymatic system in some ethanol effects could be mediated by the endogenous opioid system. The present study assessed whether brain catalase has a role in ethanol-induced activation of the HPA axis, a neuroendocrine system modulated by the endogenous opioid neurotransmission. Swiss male mice received an intraperitoneal injection of the catalase inhibitor 3-amino-1,2,4-triazole (AT; 0-1 g/kg), and 0 to 20 hr after this administration, animals received an ethanol (0-4 g/kg; intraperitoneally) challenge. Thirty, 60, or 120 min after ethanol administration, plasma corticosterone levels were determined immunoenzymatically. In addition, we tested the effects of 45 mg/kg of cyanamide (another catalase inhibitor) and 0 to 2 mg/kg of naltrexone (nonselective opioid receptor antagonist) on ethanol-induced enhancement in plasma corticosterone values. The present study revealed that AT boosts ethanol-induced increase in plasma corticosterone levels in a dose- and time-dependent manner. However, it did not affect corticosterone values when measured after administration of saline, cocaine (4 mg/kg, intraperitoneally), or morphine (30 mg/kg, intraperitoneally). The catalase inhibitor cyanamide (45 mg/kg, intraperitoneally) also increased ethanol-related plasma corticosterone levels. These effects of AT and cyanamide on ethanol-induced corticosterone values were observed under treatment conditions that decreased significantly brain catalase activity. Indeed, a significant correlation between effects of catalase manipulations on both variables was found. Finally, we found that the administration of naltrexone enhanced the levels of plasma corticosterone after the administration of saline or ethanol. This study shows that the inhibition of brain catalase increases ethanol-induced plasma corticosterone levels. Results are

Increased CD147 (EMMPRIN) expression in the rat brain following traumatic brain injury.

Science.gov (United States)

Wei, Ming; Li, Hong; Shang, Yanguo; Zhou, Ziwei; Zhang, Jianning

2014-10-17

The extracellular matrix metalloproteinase inducer (EMMPRIN), or CD147, has been known to play a key regulatory role in vascular permeability and leukocyte activation by inducing the expression of matrix metalloproteinases (MMPs). The effects of traumatic brain injury on the expression of EMMPRIN remain poorly understood. In this study, we investigated changes in EMMPRIN expression in a rat model of fluid percussion injury (FPI) and examined the potential association between EMMPRIN and MMP-9 expression. Adult male rats were subjected to FPI. EMMPRIN expression was markedly up-regulated in the brain tissue surrounding the injured region 6-48 h after TBI, as measured by immunoblot and immunohistochemistry. EMMPRIN expression was localized to inflammatory cells. The increase in EMMPRIN expression was temporally correlated with an increase in MMP-9 levels. These data demonstrate, for the first time, changes in CD147 and MMP-9 expression following TBI. These data also suggest that CD147 and MMP-9 may play a role in vascular injuries after TBI. Copyright © 2014 Elsevier B.V. All rights reserved.

Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running.

Science.gov (United States)

Johnson, R A; Rhodes, J S; Jeffrey, S L; Garland, T; Mitchell, G S

2003-01-01

Voluntary wheel running in rats increases hippocampal brain-derived neurotrophic factor (BDNF) expression, a neurochemical important for neuronal survival, differentiation, connectivity and synaptic plasticity. Here, we report the effects of wheel running on BDNF and neurotrophin-3 (NT-3) protein levels in normal control mice, and in mice selectively bred (25 generations) for increased voluntary wheel running. We hypothesized that increased voluntary wheel running in selected (S) mice would increase CNS BDNF and NT-3 protein levels more than in control (C) mice. Baseline hippocampal BDNF levels (mice housed without running wheels) were similar in S and C mice. Following seven nights of running, hippocampal BDNF increased significantly more in S versus C mice, and levels were correlated with distance run (considering C and S mice together). Spinal and cerebellar BDNF and hippocampal NT-3 levels were not significantly affected by wheel running in any group, but there was a small, positive correlation between spinal C3-C6 BDNF levels and distance run (considering C and S mice together). This is the first study to demonstrate that mice which choose to run more have greater elevations in hippocampal BDNF, suggesting enhanced potential for exercise-induced hippocampal neuroplasticity.

Increased Intracranial Pressure during Hemodialysis in a Patient with Anoxic Brain Injury

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Lund, Anton; Damholt, Mette B; Strange, Ditte G

2017-01-01

Dialysis disequilibrium syndrome (DDS) is a serious neurological complication of hemodialysis, and patients with acute brain injury are at increased risk. We report a case of DDS leading to intracranial hypertension in a patient with anoxic brain injury and discuss the subsequent dialysis strateg...

Increased White Matter Inflammation in Aging- and Alzheimer’s Disease Brain

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Divya Raj

2017-06-01

Full Text Available Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer’s disease (AD-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis and HLA-DR (associated with antigen presentation, in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years. This early inflammation was also detectable by non-invasive positron emission tomography imaging using [11C]-(R-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

Clinical significance of determination of serum NSE and plasma ET, IGF-II, CNP levels in patients with acute brain injury

International Nuclear Information System (INIS)

Chen Bo

2010-01-01

Objective: To investigate the clinical significance of changes of plasma ET, IGF-II, CNP and serum NSE contents in patients with acute brain injury. Methods: Serum contents of neuron specific enolase (NSE) were measured with chemiluminescence immunoassay and plasma endothelin (ET), insulin-like growth factor-II (IGF-II) and C-type natriuretic peptide (CNP) were measured with radioimmunoassay in 30 patients with acute brain injury and 35 controls. Results: Serum contents of NSE and plasma IGF-II, CNP were not much different in patients with mild brain injury from those in controls (P >0.05), but plasma contents of ET were already significantly higher in patients with mild brain injury than those in controls(P < 0.01). The serum NSE and plasma ET levels in patients with moderate and severe brain injury were significantly higher than those in patients with mild brain injury and controls (P < 0.01). Decrease of plasma levels of IGF-II and CNP was not significant in patients with mild brain injury (vs controls). However, the plasma levels of IGF-II and CNP were significantly lower in patients with moderate and severe brain injury than those in patients with mild brain injury and controls (P <0.01). As a whole, the magnitude of changes of these parameters was proportional to the severity of the injury. Conclusion: Changes of serum NSE and plasma IGF-II, ET and CNP levels were closely related to the pathological process of brain injury. Determination of these parameters was of clinical importance for evaluation of the severity of injury and outcome prediction. (authors)

Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

Science.gov (United States)

Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

2015-01-01

Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

Institute of Scientific and Technical Information of China (English)

HuaHu; Wei-PingZhang; LeiZhang; ZhongChen; Er-QingWei

2004-01-01

Aquaporin-4 (AQP4) is one of the aquaporins (AQPs), a water channel family. In the brain, AQP4 is expressed in astroeyte foot processes, and plays an important role in water homeostasis and in the formation of brain edema. In our study, AQP4 expression in human brain specimens from patients with traumatic brain injury or different brain tumors was detected

Risperidone treatment increases CB1 receptor binding in rat brain

DEFF Research Database (Denmark)

Secher, Anna; Husum, Henriette; Holst, Birgitte

2010-01-01

, the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone. METHODS: Male Sprague-Dawley rats were treated with risperidone (1.0 mg/kg/day) or vehicle (20...... showed that risperidone treatment altered CB(1) receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB(1) receptor density in brain regions involved in appetite and regulation of metabolic function....

Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

Science.gov (United States)

Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

2015-02-01

Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

The Paravascular Pathway for Brain Waste Clearance: Current Understanding, Significance and Controversy

Directory of Open Access Journals (Sweden)

Andrew Bacyinski

2017-11-01

Full Text Available The paravascular pathway, also known as the “glymphatic” pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF and solutes in the parenchyma, and exits along paravascular spaces of draining veins. Studies have shown that metabolic waste products and solutes, including proteins involved in the pathogenesis of neurodegenerative diseases such as amyloid-beta, may be cleared by this pathway. Consequently, a growing body of research has begun to explore the association between glymphatic dysfunction and various disease states. However, significant controversy exists in the literature regarding both the direction of waste clearance as well as the anatomical space in which the waste-fluid mixture is contained. Some studies have found no evidence of interstitial solute clearance along the paravascular space of veins. Rather, they demonstrate a perivascular pathway in which waste is cleared from the brain along an anatomically distinct perivascular space in a direction opposite to that of paravascular flow. Although possible explanations have been offered, none have been able to fully reconcile the discrepancies in the literature, and many questions remain. Given the therapeutic potential that a comprehensive understanding of brain waste clearance pathways might offer, further research and clarification is highly warranted.

The Paravascular Pathway for Brain Waste Clearance: Current Understanding, Significance and Controversy.

Science.gov (United States)

Bacyinski, Andrew; Xu, Maosheng; Wang, Wei; Hu, Jiani

2017-01-01

The paravascular pathway, also known as the "glymphatic" pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF) enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF) and solutes in the parenchyma, and exits along paravascular spaces of draining veins. Studies have shown that metabolic waste products and solutes, including proteins involved in the pathogenesis of neurodegenerative diseases such as amyloid-beta, may be cleared by this pathway. Consequently, a growing body of research has begun to explore the association between glymphatic dysfunction and various disease states. However, significant controversy exists in the literature regarding both the direction of waste clearance as well as the anatomical space in which the waste-fluid mixture is contained. Some studies have found no evidence of interstitial solute clearance along the paravascular space of veins. Rather, they demonstrate a perivascular pathway in which waste is cleared from the brain along an anatomically distinct perivascular space in a direction opposite to that of paravascular flow. Although possible explanations have been offered, none have been able to fully reconcile the discrepancies in the literature, and many questions remain. Given the therapeutic potential that a comprehensive understanding of brain waste clearance pathways might offer, further research and clarification is highly warranted.

Brain atrophy during aging

International Nuclear Information System (INIS)

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

1985-01-01

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

Increasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid

Directory of Open Access Journals (Sweden)

Ryan C. Bates

2015-08-01

Full Text Available Neural tissue exposure to valproic acid (VPA increases several pro-survival phospho-proteins that can be used as biomarkers for indicating a beneficial drug response (pAktSer473, pGSK3βSer9, pErk1/2Thr202/Tyr204. Unfortunately, targeting VPA to neural tissue is a problem due to severe asymmetrical distribution, wherein the drug tends to remain in peripheral blood rather than localizing within the brain. Intracerebral delivery of an amide-linked VPA–PEG conjugate could address these issues by enhancing retention and promoting cerebro-global increases in pro-survival phospho-proteins. It is necessary to assay for the retained bioactivity of a PEGylated valproic acid molecule, along with locating an intracranial cannula placement that optimizes the increase of a known downstream biomarker for chronic VPA exposure. Here we show an acute injection of VPA–PEG conjugate within brain tissue increased virtually all of the assayed phospho-proteins, including well-known pro-survival factors. In contrast, an acute injection of VPA expectedly decreased signaling throughout the hour. Needle penetration into whole brain tissue is the intentional cause of trauma in this procedure. The trauma to brain tissue was observed to overcome known phospho-protein increases for unmodified VPA in the injected solution, while VPA–PEG conjugate appeared to induce significant increases in pro-survival phospho-proteins, despite the procedural trauma.

Incidence and prognostic significance of postoperative complications demonstrated on CT after brain tumor removal

Energy Technology Data Exchange (ETDEWEB)

Fukamachi, Akira; Koizumi, Hidehito; Kimura, Ryoichi; Nukui, Hideaki; Kunimine, Hideo

1987-06-01

We surveyed the computed tomographic (CT) findings in 273 patients who had undergone 301 craniotomies for brain tumors to determine the incidence and clinical outcome of the postoperative complications demonstrated on CT. The frequencies of medium-sized or large postoperative lesions were as follows: intracerebral hemorrhage, 11% of 301 operations; subdural fluid collection, 8%; brain edema, 6%; extradural hemorrhage, 4%; cerebral infarction, 3%; ventricular enlargement, 3%; intraventricular hemorrhage, 2%; chronic subdural hematoma, 1%; porencephalic cyst, 0.7%; tension pneumocephalus, 0.7%. In association with these complications, poor outcomes (deaths) developed with the following frequencies: intracerebral hemorrhage including an association with other types of hemorrhage, 4% (deaths, 2%) of 301 operations; cerebral infarction, 1% (deaths, 0.7%); brain edema, 0.7% (deaths, 0.7%); simple intraventricular hemorrhage, 0.3% (no deaths); tension pneumocephalus, 0.3% (no deaths). From these results, we conclude that medium-sized or large intracerebral hemorrhage, massive cerebral infarction and edema have a grave clinical significance in the postoperative course of patients with brain tumors.

Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats

DEFF Research Database (Denmark)

Bjerring, Peter Nissen; Dale, Nicholas; Larsen, Fin Stolze

2015-01-01

) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18......Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found...... in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP...

Clinical significance of I-123 IMP brain SPECT in children with brain diseases

International Nuclear Information System (INIS)

Takishima, Teruo; Machida, Kikuo; Honda, Norinari; Mamiya, Toshio; Takahashi, Taku; Kamano, Tsuyoshi; Hasegawa, Noriko

1990-01-01

Single photon emission computed tomography (SPECT) of the brain using N-isopropyl p-I-123-iodoamphetamine (I-123 IMP) was performed in 43 children with suspected brain diseases. Forty-three children (25 males and 18 females), with an age range of 24 days-15 years (mean: 6.6 years), were included in the study. Six patients were subsequently diagnosed as normal. Early SPECT of the brain was performed 30 minutes after intravenous administration of 74-111 MBq (2-3 mCi) I-123 IMP using a rotating gamma camera equipped with a 30-degree slant hole and medium energy collimator. Transverse images were reconstructed by Shepp-Logan filtered back projection method with attenuation correction after spatial filtering using an 8th order Butterworth-Wiener filter. Findings of I-123 IMP SPECT were compared with those of X-ray computed tomography (CT) and electroencephalography (EEG). The results showed that in I-123 IMP SPECT, abnormality was found in 30 out of 37 children with brain diseases. The incidence of abnormal findings in the 37 patients was 81% in I-123 IMP SPECT, 61% in X-ray CT, and 78% in EEG; in both cryptogenic and secondary epilepsy, the incidence of abnormality was higher in I-123 IMP SPECT than in X-ray CT. (70% and 94% vs 50% and 81% respectively), and epileptic foci detected by EEG did not correspond with defects found using I-123 IMP SPECT in 27% of the patients; and in asphyxiated infants, a high incidence of abnormality was observed on both I-123 IMP SPECT (86%) and X-ray CT (86%). In conclusion, I-123 IMP SPECT is a clinically useful examination in children with brain disease. (author)

Repeated intravenous administration of gadobutrol does not lead to increased signal intensity on unenhanced T1-weighted images - a voxel-based whole brain analysis

Energy Technology Data Exchange (ETDEWEB)

Langner, Soenke; Kromrey, Marie-Luise [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Kuehn, Jens-Peter [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); University Hospital, Carl Gustav Carus University Dresden, Institute for Radiology, Dresden (Germany); Grothe, Matthias [University Medicine Greifswald, Department of Neurology, Greifswald (Germany); Domin, Martin [University Medicine Greifswald, Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany)

2017-09-15

To identify a possible association between repeated intravenous administration of gadobutrol and increased signal intensity in the grey and white matter using voxel-based whole-brain analysis. In this retrospective single-centre study, 217 patients with a clinically isolated syndrome underwent baseline brain magnetic resonance imaging and at least one annual follow-up examination with intravenous administration of 0.1 mmol/kg body weight of gadobutrol. Using the ''Diffeomorphic Anatomical Registration using Exponentiated Lie algebra'' (DARTEL) normalisation process, tissue templates for grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were calculated, as were GM-CSF and WM-CSF ratios. Voxel-based whole-brain analysis was used to calculate the signal intensity for each voxel in each data set. Paired t-test was applied to test differences to baseline MRI for significance. Voxel-based whole-brain analysis demonstrated no significant changes in signal intensity of grey and white matter after up to five gadobutrol administrations. There was no significant change in GM-CSF and grey WM-CSF ratios. Voxel-based whole-brain analysis did not demonstrate increased signal intensity of GM and WM on unenhanced T1-weighted images after repeated gadobutrol administration. The molecular structure of gadolinium-based contrast agent preparations may be an essential factor causing SI increase on unenhanced T1-weighted images. (orig.)

Gas revenue increasingly significant

International Nuclear Information System (INIS)

Megill, R.E.

1991-01-01

This paper briefly describes the wellhead prices of natural gas compared to crude oil over the past 70 years. Although natural gas prices have never reached price parity with crude oil, the relative value of a gas BTU has been increasing. It is one of the reasons that the total amount of money coming from natural gas wells is becoming more significant. From 1920 to 1955 the revenue at the wellhead for natural gas was only about 10% of the money received by producers. Most of the money needed for exploration, development, and production came from crude oil. At present, however, over 40% of the money from the upstream portion of the petroleum industry is from natural gas. As a result, in a few short years natural gas may become 50% of the money revenues generated from wellhead production facilities

Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

OpenAIRE

Nagendra Sanyasihally Ningaraj; Divya eKhaitan

2013-01-01

Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB) not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB). Studies in our laboratory have identifi...

Aggravation of brain infarction through an increase in acrolein production and a decrease in glutathione with aging.

Science.gov (United States)

Uemura, Takeshi; Watanabe, Kenta; Ishibashi, Misaki; Saiki, Ryotaro; Kuni, Kyoshiro; Nishimura, Kazuhiro; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

2016-04-29

We previously reported that tissue damage during brain infarction was mainly caused by inactivation of proteins by acrolein. This time, it was tested why brain infarction increases in parallel with aging. A mouse model of photochemically induced thrombosis (PIT) was studied using 2, 6, and 12 month-old female C57BL/6 mice. The size of brain infarction in the mouse PIT model increased with aging. The volume of brain infarction in 12 month-old mice was approximately 2-fold larger than that in 2 month-old mice. The larger brain infarction in 12 month-old mice was due to an increase in acrolein based on an increase in the activity of spermine oxidase, together with a decrease in glutathione (GSH), a major acrolein-detoxifying compound in cells, based on the decrease in one of the subunits of glutathione biosynthesizing enzymes, γ-glutamylcysteine ligase modifier subunit, with aging. The results indicate that aggravation of brain infarction with aging was mainly due to the increase in acrolein production and the decrease in GSH in brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Incidence and prognostic significance of postoperative complications demonstrated on CT after brain tumor removal

International Nuclear Information System (INIS)

Fukamachi, Akira; Koizumi, Hidehito; Kimura, Ryoichi; Nukui, Hideaki; Kunimine, Hideo.

1987-01-01

We surveyed the computed tomographic (CT) findings in 273 patients who had undergone 301 craniotomies for brain tumors to determine the incidence and clinical outcome of the postoperative complications demonstrated on CT. The frequencies of medium-sized or large postoperative lesions were as follows: intracerebral hemorrhage, 11 % of 301 operations; subdural fluid collection, 8 %; brain edema, 6 %; extradural hemorrhage, 4 %; cerebral infarction, 3 %; ventricular enlargement, 3 %; intraventricular hemorrhage, 2 %; chronic subdural hematoma, 1 %; porencephalic cyst, 0.7 %; tension pneumocephalus, 0.7 %. In association with these complications, poor outcomes (deaths) developed with the following frequencies: intracerebral hemorrhage including an association with other types of hemorrhage, 4 % (deaths, 2 %) of 301 operations; cerebral infarction, 1 % (deaths, 0.7 %); brain edema, 0.7 % (deaths, 0.7 %); simple intraventricular hemorrhage, 0.3 % (no deaths); tension pneumocephalus, 0.3 % (no deaths). From these results, we conclude that medium-sized or large intracerebral hemorrhage, massive cerebral infarction and edema have a grave clinical significance in the postoperative course of patients with brain tumors. (author)

Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

Directory of Open Access Journals (Sweden)

Haider Raza

2015-02-01

Full Text Available Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS production in the ZDF rat brain compared to the liver, while nitric oxide (NO production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

Increased KPI containing amyloid precursor protein in experimental autoimmune encephalomyelitis brains.

Science.gov (United States)

Beilin, Orit; Karussis, Dimitrios M; Korczyn, Amos D; Gurwitz, David; Aronovich, Ramona; Mizrachi-Kol, Rachel; Chapman, Joab

2007-04-16

Amyloid precursor protein can be translated from three alternatively spliced mRNAs. We measured levels of amyloid precursor protein isoforms containing the Kunitz protease inhibitor domain (KPIAPP), and amyloid precursor protein without the Kunitz protease inhibitor domain (KPIAPP) in brain homogenates of acute experimental autoimmune encephalomyelitis mice. At the preclinical phase of the disease, both KPIAPP and KPIAPP levels were significantly higher in homogenates from brains of autoimmune encephalomyelitis mice, whereas at the acute phase of the disease only KPIAPP remained significantly elevated compared with controls. At the recovery phase, no differences were observed between the groups. The early and isoform-specific elevation of KPIAPP in autoimmune encephalomyelitis mice suggests a possible role for amyloid precursor protein in the immune response mediating the disease.

Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model.

Science.gov (United States)

Son, Seung-Wan; Lee, Jin-Seok; Kim, Hyeong-Geug; Kim, Dong-Woon; Ahn, Yo-Chan; Son, Chang-Gue

2016-01-01

Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re-divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint-induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4-hydroxynonenal staining for oxidative injury and Fluoro-Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions. Unlike estrogen, the effects of testosterone on the brain have not been thoroughly investigated. In order to investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. Orchiectomy markedly augmented the restraint stress-induced elevation of serum corticosterone and adrenaline levels as well as oxidative alterations

Soman poisoning increases neural progenitor proliferation and induces long-term glial activation in mouse brain

International Nuclear Information System (INIS)

Collombet, Jean-Marc; Four, Elise; Bernabe, Denis; Masqueliez, Catherine; Burckhart, Marie-France; Baille, Valerie; Baubichon, Dominique; Lallement, Guy

2005-01-01

To date, only short-term glial reaction has been extensively studied following soman or other warfare neurotoxicant poisoning. In a context of cell therapy by neural progenitor engraftment to repair brain damage, the long-term effect of soman on glial reaction and neural progenitor division was analyzed in the present study. The effect of soman poisoning was estimated in mouse brains at various times ranging from 1 to 90 days post-poisoning. Using immunochemistry and dye staining techniques (hemalun-eosin staining), the number of degenerating neurons, the number of dividing neural progenitors, and microglial, astroglial or oligodendroglial cell activation were studied. Soman poisoning led to rapid and massive (post-soman day 1) death of mature neurons as assessed by hemalun-eosin staining. Following this acute poisoning phase, a weak toxicity effect on mature neurons was still observed for a period of 1 month after poisoning. A massive short-termed microgliosis peaked on day 3 post-poisoning. Delayed astrogliosis was observed from 3 to 90 days after soman poisoning, contributing to glial scar formation. On the other hand, oligodendroglial cells or their precursors were practically unaffected by soman poisoning. Interestingly, neural progenitors located in the subgranular zone of the dentate gyrus (SGZ) or in the subventricular zone (SVZ) of the brain survived soman poisoning. Furthermore, soman poisoning significantly increased neural progenitor proliferation in both SGZ and SVZ brain areas on post-soman day 3 or day 8, respectively. This increased proliferation rate was detected up to 1 month after poisoning

SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

International Nuclear Information System (INIS)

Hossain, S; Hildebrand, K; Ahmad, S; Larson, D; Ma, L; Sahgal, A

2014-01-01

Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targets were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery

Clinical significance of measurement of plasma ET-1 and CGRP levels in patients with traumatic brain injury

International Nuclear Information System (INIS)

Jing Daping; Cheng Guanghua

2007-01-01

Objective: To study the changes of plasma ET-1 and CGRP levels in patients with traumatic brain injury of different severity. Methods: 107 patients with traumatic brain injury were divided into three group on the basis of GCS: mild group (n=25, GCS>12), moderate group (n=33, GCS9-12) and severe group (n=49, GCS3-8). The plasma ET-1 and CGRP levels in these patients and 30 controls were determined with RIA. Results: 1) The plasma ET-1 levels in patients with traumatic brain injury were signilieantly higher than those in controls, the more severe the illness, the higher the ET-1 levels. 2)The plasma CGRP levels in patients of mild and moderate brain injury were found significantly higher than those in controls, while no significant differences were found between those in severe and control group. 3)The more severe the illness was, the lower CGRP/ET-1 ratio were found. Conclusion: The changes of plasma levels of ET-1 and CGRP and the CGRP/ET-1 ratio in the patients with traumatic brain injury were correlated with the severity of the illness, and might be of prognostic value. (authors)

Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura

DEFF Research Database (Denmark)

Hougaard, Anders; Amin, Faisal M; Christensen, Casper E

2017-01-01

symptoms are related to the headache phase of migraine. Animal studies suggest that cortical spreading depression, the likely mechanism of migraine aura, causes disruption of the blood-brain barrier and noxious stimulation of trigeminal afferents leading to activation of brainstem nuclei and triggering...... of migraine headache. We used the sensitive and validated technique of dynamic contrast-enhanced high-field magnetic resonance imaging to simultaneously investigate blood-brain barrier permeability and tissue perfusion in the brainstem (at the level of the lower pons), visual cortex, and brain areas......-free day. The mean time from attack onset to scanning was 7.6 h. We found increased brainstem perfusion bilaterally during migraine with aura attacks. Perfusion also increased in the visual cortex and posterior white matter following migraine aura. We found no increase in blood-brain barrier permeability...

Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer

DEFF Research Database (Denmark)

Fabian, Katalin; Gyulai, Marton; Furak, Jozsef

2016-01-01

Background: Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life-threatening complications. Methods: We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive...... lung cancer patients with brain metastases. Results: In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p ... of peritumoral brain edema (p

Brain Cell Swelling During Hypocapnia Increases with Hyperglycemia or Ketosis

Science.gov (United States)

Glaser, Nicole; Bundros, Angeliki; Anderson, Steve; Tancredi, Daniel; Lo, Weei; Orgain, Myra; O'Donnell, Martha

2014-01-01

Severe hypocapnia increases the risk of DKA-related cerebral injury in children, but the reason for this association is unclear. To determine whether the effects of hypocapnia on the brain are altered during hyperglycemia or ketosis, we induced hypocapnia (pCO2 20 ± 3 mmHg) via mechanical ventilation in three groups of juvenile rats: 25 controls, 22 hyperglycemic rats (serum glucose 451± 78 mg/dL) and 15 ketotic rats (beta-hydroxy butyrate 3.0 ± 1.0 mmol/L). We used magnetic resonance imaging to measure cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) values in these groups and in 17 ventilated rats with normal pCO2 (40±3 mmHg). In a subset (n=35), after 2 hrs of hypocapnia, pCO2 levels were normalized (40±3 mmHg) and ADC and CBF measurements repeated. Declines in CBF with hypocapnia occurred in all groups. Normalization of pCO2 after hypocapnia resulted in striatal hyperemia. These effects were not substantially altered by hyperglycemia or ketosis, however, declines in ADC during hypocapnia were greater during both hyperglycemia and ketosis. We conclude that brain cell swelling associated with hypocapnia is increased by both hyperglycemia and ketosis, suggesting that these metabolic conditions may make the brain more vulnerable to injury during hypocapnia. PMID:24443981

Brain herniations into the dural venous sinus or calvarium: MRI findings, possible causes and clinical significance

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Battal, Bilal; Hamcan, Salih; Akgun, Veysel; Sari, Sebahattin; Tasar, Mustafa [Gulhane Military Medical School, Department of Radiology, Ankara (Turkey); Oz, Oguzhan [Gulhane Military Medical School, Department of Neurology, Ankara (Turkey); Castillo, Mauricio [University of North Carolina School of Medicine, Division of Neuroradiology, Department of Radiology, Chapel Hill, NC (United States)

2016-06-15

To determine frequency, imaging features and clinical significance of herniations of brain parenchyma into dural venous sinuses (DVS) and/or calvarium found on MRI. A total of 6160 brain MRI examinations containing at least one high-resolution T1- or T2-weighted sequence were retrospectively evaluated to determine the presence of incidental brain herniations into the DVS or calvarium. MRI sequences available for review were evaluated according to their capability to demonstrate these herniations. Patients' symptoms and clinical findings were recorded. Twenty-one (0.32 %) brain parenchyma herniations into the DVS (n = 18) or calvarium (n = 3) in 20 patients were detected. The most common locations of the herniations were the transverse sinuses (n = 13) and those involving inferior gyrus of the temporal lobe (n = 9). High-resolution T1- and T2-weighted sequences were equally useful in the detection of these brain herniations. According to clinical symptoms, brain herniations were considered to be incidental but headaches were present in nine patients. Brain herniations with surrounding cerebrospinal fluid (CSF) into the DVS and/or calvarium are incidental findings and not proven to be associated with any symptoms. Although rare, these herniations are more common than previously recognized and should not be confused with arachnoid granulations, clots or tumours. (orig.)

The significance of the subplate for evolution and developmental plasticity of the human brain.

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Judaš, Miloš; Sedmak, Goran; Kostović, Ivica

2013-01-01

The human life-history is characterized by long development and introduction of new developmental stages, such as childhood and adolescence. The developing brain had important role in these life-history changes because it is expensive tissue which uses up to 80% of resting metabolic rate (RMR) in the newborn and continues to use almost 50% of it during the first 5 postnatal years. Our hominid ancestors managed to lift-up metabolic constraints to increase in brain size by several interrelated ecological, behavioral and social adaptations, such as dietary change, invention of cooking, creation of family-bonded reproductive units, and life-history changes. This opened new vistas for the developing brain, because it became possible to metabolically support transient patterns of brain organization as well as developmental brain plasticity for much longer period and with much greater number of neurons and connectivity combinations in comparison to apes. This included the shaping of cortical connections through the interaction with infant's social environment, which probably enhanced typically human evolution of language, cognition and self-awareness. In this review, we propose that the transient subplate zone and its postnatal remnant (interstitial neurons of the gyral white matter) probably served as the main playground for evolution of these developmental shifts, and describe various features that makes human subplate uniquely positioned to have such a role in comparison with other primates.

THE SIGNIFICANCE OF THE SUBPLATE FOR EVOLUTION AND DEVELOPMENTAL PLASTICITY OF THE HUMAN BRAIN

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MILOS eJUDAS

2013-08-01

Full Text Available The human life-history is characterized by long development and introduction of new developmental stages, such as childhood and adolescence. The developing brain had important role in these life-history changes because it is expensive tissue which uses up to 80% of resting metabolic rate in the newborn and continues to use almost 50% of it during the first 5 postnatal years. Our hominid ancestors managed to lift-up metabolic constraints to increase in brain size by several interrelated ecological, behavioral and social adaptations, such as dietary change, invention of cooking, creation of family-bonded reproductive units, and life-history changes. This opened new vistas for the developing brain, because it became possible to metabolically support transient patterns of brain organization as well as developmental brain plasticity for much longer period and with much greater number of neurons and connectivity combinations in comparison to apes. This included the shaping of cortical connections through the interaction with infant's social environment, which probably enhanced typically human evolution of language, cognition and self-awareness. In this review, we propose that the transient subplate zone and its postnatal remnant (interstitial neurons of the gyral white matter probably served as the main playground for evolution of these developmental shifts, and describe various features that makes human subplate uniquely positioned to have such a role in comparison with other primates.

The expression and significance of tyrosine hydroxylase in the brain tissue of Parkinsons disease rats

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Chen, Yuan; Lian, Yajun; Ma, Yunqing; Wu, Chuanjie; Zheng, Yake; Xie, Nanchang

2017-01-01

The expression and significance of tyrosine hydroxylase (TH) in brain tissue of rats with Parkinson's disease (PD) were explored and analyzed. A total of 120 clean-grade and healthy adult Wistar rats weighing 180–240 g were randomly divided equally into four groups according to the random number table method. Rats were sacrificed before and after the model establishment for 3, 6 or 8 weeks. The number of revolutions in rats was observed and the relative expression of TH mRNA in brain tissue w...

Contribution of Histologic Chorioamnionitis and Fetal Inflammatory Response Syndrome to Increased Risk of Brain Injury in Infants With Preterm Premature Rupture of Membranes.

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Lu, Hong-Yan; Zhang, Qiang; Wang, Qiu-Xia; Lu, Jun-Ying

2016-08-01

To determine the association of histologic chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) with brain injuries in infants born to mothers with preterm premature rupture of membranes. A total of 103 singleton infants born to mothers with preterm premature rupture of membranes were enrolled. The placental inflammation was confirmed by HCA, and FIRS was defined in fetuses with preterm labor and an elevation of the fetal plasma interleukin-6 concentration. Examination of brain images was conducted to confirm the existence of brain injuries. Based on placental HCA and umbilical cord blood interleukin-6 level, all patients were divided into three groups: HCA(-)FIRS(+), HCA(+)FIRS(-), and HCA(+)FIRS(+). Among all infants with preterm premature rupture of membranes, 53.40% were exposed to HCA, 20.38% experienced FIRS, and the overall incidence of brain injuries was 38.83%. The incidence of brain injury in HCA(-)FIRS(+), HCA(+)FIRS(-), and HCA(+)FIRS(+) groups were 20.83%, 41.18%, and 76.19%, respectively. HCA at the advanced grades and stages was associated with increased risk of brain injury. Umbilical cord blood levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and granulocyte-colony stimulating factor (G-CSF) in premature infants with brain injuries were significantly higher than in those without brain injuries. Infants diagnosed with both HCA and FIRS showed significantly higher levels of IL-8, TNF-α, and G-CSF than those with HCA alone. Preterm infants exposed to severe chorioamnionitis had an increased risk of brain injury. IL-6, IL-8, TNF-α, and G-CSF in cord blood were associated with brain injuries in preterm infants and may be used as extradiagnostic criteria. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased Sleep Need and Reduction of Tuberomammillary Histamine Neurons after Rodent Traumatic Brain Injury.

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Noain, Daniela; Büchele, Fabian; Schreglmann, Sebastian R; Valko, Philipp O; Gavrilov, Yuri V; Morawska, Marta M; Imbach, Lukas L; Baumann, Christian R

2018-01-01

Although sleep-wake disturbances are prevalent and well described after traumatic brain injury, their pathophysiology remains unclear, most likely because human traumatic brain injury is a highly heterogeneous entity that makes the systematic study of sleep-wake disturbances in relation to trauma-induced histological changes a challenging task. Despite increasing interest, specific and effective treatment strategies for post-traumatic sleep-wake disturbances are still missing. With the present work, therefore, we aimed at studying acute and chronic sleep-wake disturbances by electrophysiological means, and at assessing their histological correlates after closed diffuse traumatic brain injury in rats with the ultimate goal of generating a model of post-traumatic sleep-wake disturbances and associated histopathological findings that accurately represents the human condition. We assessed sleep-wake behavior by means of standard electrophysiological recordings before and 1, 7, and 28 days after sham or traumatic brain injury procedures. Sleep-wake findings were then correlated to immunohistochemically labeled and stereologically quantified neuronal arousal systems. Compared with control animals, we found that closed diffuse traumatic brain injury caused increased sleep need one month after trauma, and sleep was more consolidated. As histological correlate, we found a reduced number of histamine immunoreactive cells in the tuberomammillary nucleus, potentially related to increased neuroinflammation. Monoaminergic and hypocretinergic neurotransmitter systems in the hypothalamus and rostral brainstem were not affected, however. These results suggest that our rat traumatic brain injury model reflects human post-traumatic sleep-wake disturbances and associated histopathological findings very accurately, thus providing a study platform for novel treatment strategies for affected patients.

Increased brain iron deposition is a risk factor for brain atrophy in patients with haemodialysis: a combined study of quantitative susceptibility mapping and whole brain volume analysis.

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Chai, Chao; Zhang, Mengjie; Long, Miaomiao; Chu, Zhiqiang; Wang, Tong; Wang, Lijun; Guo, Yu; Yan, Shuo; Haacke, E Mark; Shen, Wen; Xia, Shuang

2015-08-01

To explore the correlation between increased brain iron deposition and brain atrophy in patients with haemodialysis and their correlation with clinical biomarkers and neuropsychological test. Forty two patients with haemodialysis and forty one age- and gender-matched healthy controls were recruited in this prospective study. 3D whole brain high resolution T1WI and susceptibility weighted imaging were scanned on a 3 T MRI system. The brain volume was analyzed using voxel-based morphometry (VBM) in patients and to compare with that of healthy controls. Quantitative susceptibility mapping was used to measure and compare the susceptibility of different structures between patients and healthy controls. Correlation analysis was used to investigate the relationship between the brain volume, iron deposition and neuropsychological scores. Stepwise multiple regression analysis was used to explore the effect of clinical biomarkers on the brain volumes in patients. Compared with healthy controls, patients with haemodialysis showed decreased volume of bilateral putamen and left insular lobe (All P brain iron deposition is negatively correlated with the decreased volume of bilateral putamen (P brain iron deposition and dialysis duration was risk factors for brain atrophy in patients with haemodialysis. The decreased gray matter volume of the left insular lobe was correlated with neurocognitive impairment.

Wnt3a upregulates brain-derived insulin by increasing NeuroD1 via Wnt/β-catenin signaling in the hypothalamus.

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Lee, Jaemeun; Kim, Kyungchan; Yu, Seong-Woon; Kim, Eun-Kyoung

2016-03-08

Insulin plays diverse roles in the brain. Although insulin produced by pancreatic β-cells that crosses the blood-brain barrier is a major source of brain insulin, recent studies suggest that insulin is also produced locally within the brain. However, the mechanisms underlying the production of brain-derived insulin (BDI) are not yet known. Here, we examined the effect of Wnt3a on BDI production in a hypothalamic cell line and hypothalamic tissue. In N39 hypothalamic cells, Wnt3a treatment significantly increased the expression of the Ins2 gene, which encodes the insulin isoform predominant in the mouse brain, by activating Wnt/β-catenin signaling. The concentration of insulin was higher in culture medium of Wnt3a-treated cells than in that of untreated cells. Interestingly, neurogenic differentiation 1 (NeuroD1), a target of Wnt/β-catenin signaling and one of transcription factors for insulin, was also induced by Wnt3a treatment in a time- and dose-dependent manner. In addition, the treatment of BIO, a GSK3 inhibitor, also increased the expression of Ins2 and NeuroD1. Knockdown of NeuroD1 by lentiviral shRNAs reduced the basal expression of Ins2 and suppressed Wnt3a-induced Ins2 expression. To confirm the Wnt3a-induced increase in Ins2 expression in vivo, Wnt3a was injected into the hypothalamus of mice. Wnt3a increased the expression of NeuroD1 and Ins2 in the hypothalamus in a manner similar to that observed in vitro. Taken together, these results suggest that BDI production is regulated by the Wnt/β-catenin/NeuroD1 pathway in the hypothalamus. Our findings will help to unravel the regulation of BDI production in the hypothalamus.

Defective insulin signaling pathway and increased glycogen synthase kinase-3 activity in the brain of diabetic mice: parallels with Alzheimer's disease and correction by insulin.

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Jolivalt, C G; Lee, C A; Beiswenger, K K; Smith, J L; Orlov, M; Torrance, M A; Masliah, E

2008-11-15

We have evaluated the effect of peripheral insulin deficiency on brain insulin pathway activity in a mouse model of type 1 diabetes, the parallels with Alzheimer's disease (AD), and the effect of treatment with insulin. Nine weeks of insulin-deficient diabetes significantly impaired the learning capacity of mice, significantly reduced insulin-degrading enzyme protein expression, and significantly reduced phosphorylation of the insulin-receptor and AKT. Phosphorylation of glycogen synthase kinase-3 (GSK3) was also significantly decreased, indicating increased GSK3 activity. This evidence of reduced insulin signaling was associated with a concomitant increase in tau phosphorylation and amyloid beta protein levels. Changes in phosphorylation levels of insulin receptor, GSK3, and tau were not observed in the brain of db/db mice, a model of type 2 diabetes, after a similar duration (8 weeks) of diabetes. Treatment with insulin from onset of diabetes partially restored the phosphorylation of insulin receptor and of GSK3, partially reduced the level of phosphorylated tau in the brain, and partially improved learning ability in insulin-deficient diabetic mice. Our data indicate that mice with systemic insulin deficiency display evidence of reduced insulin signaling pathway activity in the brain that is associated with biochemical and behavioral features of AD and that it can be corrected by insulin treatment.

Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura.

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Hougaard, Anders; Amin, Faisal M; Christensen, Casper E; Younis, Samaira; Wolfram, Frauke; Cramer, Stig P; Larsson, Henrik B W; Ashina, Messoud

2017-06-01

See Moskowitz (doi:10.1093/brain/awx099) for a scientific commentary on this article.The migraine aura is characterized by transient focal cortical disturbances causing dramatic neurological symptoms that are usually followed by migraine headache. It is currently not understood how the aura symptoms are related to the headache phase of migraine. Animal studies suggest that cortical spreading depression, the likely mechanism of migraine aura, causes disruption of the blood-brain barrier and noxious stimulation of trigeminal afferents leading to activation of brainstem nuclei and triggering of migraine headache. We used the sensitive and validated technique of dynamic contrast-enhanced high-field magnetic resonance imaging to simultaneously investigate blood-brain barrier permeability and tissue perfusion in the brainstem (at the level of the lower pons), visual cortex, and brain areas of the anterior, middle and posterior circulation during spontaneous attacks of migraine with aura. Patients reported to our institution to undergo magnetic resonance imaging during the headache phase after presenting with typical visual aura. Nineteen patients were scanned during attacks and on an attack-free day. The mean time from attack onset to scanning was 7.6 h. We found increased brainstem perfusion bilaterally during migraine with aura attacks. Perfusion also increased in the visual cortex and posterior white matter following migraine aura. We found no increase in blood-brain barrier permeability in any of the investigated regions. There was no correlation between blood-brain barrier permeability, brain perfusion, and time from symptom onset to examination or pain intensity. Our findings demonstrate hyperperfusion in brainstem during the headache phase of migraine with aura, while the blood-brain barrier remains intact during attacks of migraine with aura. These data thus contradict the preclinical hypothesis of cortical spreading depression-induced blood-brain barrier

Chernobyl birds have smaller brains.

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Anders Pape Møller

2011-02-01

Full Text Available Animals living in areas contaminated by radioactive material from Chernobyl suffer from increased oxidative stress and low levels of antioxidants. Therefore, normal development of the nervous system is jeopardized as reflected by high frequencies of developmental errors, reduced brain size and impaired cognitive abilities in humans. Alternatively, associations between psychological effects and radiation have been attributed to post-traumatic stress in humans.Here we used an extensive sample of 550 birds belonging to 48 species to test the prediction that even in the absence of post-traumatic stress, there is a negative association between relative brain size and level of background radiation. We found a negative association between brain size as reflected by external head volume and level of background radiation, independent of structural body size and body mass. The observed reduction in brain size in relation to background radiation amounted to 5% across the range of almost a factor 5,000 in radiation level. Species differed significantly in reduction in brain size with increasing background radiation, and brain size was the only morphological character that showed a negative relationship with radiation. Brain size was significantly smaller in yearlings than in older individuals.Low dose radiation can have significant effects on normal brain development as reflected by brain size and therefore potentially cognitive ability. The fact that brain size was smaller in yearlings than in older individuals implies that there was significant directional selection on brain size with individuals with larger brains experiencing a viability advantage.

Increased Intracranial Pressure during Hemodialysis in a Patient with Anoxic Brain Injury

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Anton Lund

2017-01-01

Full Text Available Dialysis disequilibrium syndrome (DDS is a serious neurological complication of hemodialysis, and patients with acute brain injury are at increased risk. We report a case of DDS leading to intracranial hypertension in a patient with anoxic brain injury and discuss the subsequent dialysis strategy. A 13-year-old girl was admitted after prolonged resuscitation from cardiac arrest. Computed tomography (CT revealed an inferior vena cava aneurysm and multiple pulmonary emboli as the likely cause. An intracranial pressure (ICP monitor was inserted, and, on day 3, continuous renal replacement therapy (CRRT was initiated due to acute kidney injury, during which the patient developed severe intracranial hypertension. CT of the brain showed diffuse cerebral edema. CRRT was discontinued, sedation was increased, and hypertonic saline was administered, upon which ICP normalized. Due to persistent hyperkalemia and overhydration, ultrafiltration and intermittent hemodialysis were performed separately on day 4 with a small dialyzer, low blood and dialysate flow, and high dialysate sodium content. During subsequent treatments, isolated ultrafiltration was well tolerated, whereas hemodialysis was associated with increased ICP necessitating frequent pauses or early cessation of dialysis. In patients at risk of DDS, hemodialysis should be performed with utmost care and continuous monitoring of ICP should be considered.

Increased Intracranial Pressure during Hemodialysis in a Patient with Anoxic Brain Injury.

Science.gov (United States)

Lund, Anton; Damholt, Mette B; Strange, Ditte G; Kelsen, Jesper; Møller-Sørensen, Hasse; Møller, Kirsten

2017-01-01

Dialysis disequilibrium syndrome (DDS) is a serious neurological complication of hemodialysis, and patients with acute brain injury are at increased risk. We report a case of DDS leading to intracranial hypertension in a patient with anoxic brain injury and discuss the subsequent dialysis strategy. A 13-year-old girl was admitted after prolonged resuscitation from cardiac arrest. Computed tomography (CT) revealed an inferior vena cava aneurysm and multiple pulmonary emboli as the likely cause. An intracranial pressure (ICP) monitor was inserted, and, on day 3, continuous renal replacement therapy (CRRT) was initiated due to acute kidney injury, during which the patient developed severe intracranial hypertension. CT of the brain showed diffuse cerebral edema. CRRT was discontinued, sedation was increased, and hypertonic saline was administered, upon which ICP normalized. Due to persistent hyperkalemia and overhydration, ultrafiltration and intermittent hemodialysis were performed separately on day 4 with a small dialyzer, low blood and dialysate flow, and high dialysate sodium content. During subsequent treatments, isolated ultrafiltration was well tolerated, whereas hemodialysis was associated with increased ICP necessitating frequent pauses or early cessation of dialysis. In patients at risk of DDS, hemodialysis should be performed with utmost care and continuous monitoring of ICP should be considered.

Relative significance of surgery and radiotherapy in treatment of brain metastases of lung cancer

International Nuclear Information System (INIS)

Yamashita, Junkoh; Ohtsuka, Sinichi; Yamasaki, Toshiki; Gi, Hidefuku; Ha, Young-Soo; Handa, Hajime

1983-01-01

One hundred and sixteen cases of brain metastases of lung cancer were retrospectively analysed with special reference to the relative significance of surgery and radiotherapy. The median survival time from diagnosis of brain metastases was 1.2 months in 27 cases without treatment, 2.5 months in 51 cases treated by surgery alone, 4.2 months in 31 cases treated by radiotherapy alone and 6.5 months in 7 cases treated by surgery and radiotherapy. The survival rate in patients treated by radiotherapy was significantly better than in those not treated by radiotherapy. However, the effect of surgery was not significant in prolongation of survival time. On the other hand, the rate of improvement in neurological symptoms assessed at one month after the initiation of treatment was 80.9% in 47 cases treated by surgery and 19.4 % in 31 cases treated by radiotherapy. The result suggested that surgery is superior to radiotherapy in alleviating neurological symptoms. It is important to understand the nature of effect of each treatment. A better result will be anticipated by proper selection or combination of these treatments. (author)

Clinical significance of determination of changes of immuno-function parameters in patients with acute severe brain lnjury on different froms of nutritional support

International Nuclear Information System (INIS)

Ma Jun; Qian Quanan; Ma Yunbao; Zhang Xiaoyi; Zhu Jin

2009-01-01

Objective: To study the relationship between different forms of nutritional support and changes of serum nutritional as well as immuno-function parameters in patients with acute severe brain injury. Methods: Serum levels of total protein, albumin, hemoglobin, transferrin (with biochemistry), immunoglobulins IgA, IgG, IgM (with immuno-turbidimetry) and cytokines IL-2, IL-6, IL-8 (with RIA) were determined in 64 patients with acute severe brain injury both before and after 7 ∼ 10ds' nutritional support. The 64 patients were divided into two groups:1) experimental group, n=30, receiving parentral (70%) plus partial enteral (30%) feedings 2) control group, n=34, receiving total parenteral untritional support exclusively with equal mitrogen and calorie intake in all the 64 patients. Results: The serum levels of total protein, albumin, Hb and transferrin as well as other parameter in both groups before nutritional support were about the same. After the course of nutritional support, the serum levels of total protein and albumin changed little in both groups, but the Hb and transferritin levels in both groups increased significantly (P<0.05) with the levels significantly higher in the experimental group than those in the control group (P also <0.05). The serum immunoglobulins IgA, IgM levels changed verd littel, except that the IgG levels increased significantly in the experimental group after treatment (P<0.05) and were significantly higher than those in control group (P also <0.05). The serum cytokins levels in the control group changed little after the course of nutritional support, but the levels in the experimental group were greatly normalized and decreased significantly after treatment (P also <0.05). Conclusion: Parenteral combined with partial enteral nutritional support could improve the nutritional as well as immuno-function status better than exclusive TPN did in patients with acute severe brain injury. (authors)

Clinical significance of changes of serum IL-6 and TNF-α levels in rat models of hypoxic-ischemia brain injury

International Nuclear Information System (INIS)

Niu Tingxian; Shi Zhiyong; Luo Jianjun

2009-01-01

Objective: To explore the clinical significance of changes of serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels in rat models of hypoxic-ischemia (HI) brain injury. Methods: Seventy five rat HI brain injury nodels were prepared with bilateral occlusion of common carotid artery for 24rs followed 2hrs later by hypoxia (breathing 8% oxygen) for 2hrs. One fifth of the animals were sacrificed at 4h, 8h, 12h, 24h and 48h later respectively, the serum and brain homogenate concentrations of IL-6 and TNF-α were determined with RIA and brain tissues were pathologically examined. Results: The concentrations of IL-6 and TNF-α were dynamically changed within 48h in serum and brain homogenate. Peak values occurred at 24h with serum and at 12h with brain homogenate. Meanwhile, levels of both cytokines were significantly higher in the models than those in controls (P<0.01 or P<0.05). Conclusion: The concentrations of IL-6 and TNF-α were dynamically(sham operation only, 15 animals) changed and might be regarded as the clinical markers of degree of HI brain injury. (authors)

What’s the clinical significance of adding diffusion and perfusion MRI in the differentiation of glioblastoma multiforme and solitary brain metastasis?

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Amr F. Mourad

2017-09-01

Full Text Available Objective: To evaluate the additional diagnostic value of diffusion and perfusion MRI in the differentiation of glioblastoma multiforme (GBM and solitary brain metastasis. Patients and methods: This retrospective study included 24 patients with histologically proven brain tumors who underwent conventional MRI with analysis of diffusion (DWI and perfusion (PWI MRI findings of each tumor. The Apparent Diffusion Coefficient (ADC values were calculated in the minimum (ADC-MIN, mean (ADC-MEAN, and maximum (ADC-MAX in all the tumors and the peritumoral regions. The PWI data was expressed as maximum regional cerebral blood volume (rCBV of the tumors and peritumoral regions. Results: After adding diffusion and perfusion to conventional MRI findings, we found that the accuracy of differentiation between glioblastoma multiforme (GBM and solitary metastasis increased from 70% to 90%.There is a significant difference in DWI signal intensity between GBM and metastatic tumors (P < 0.05. The ADC values of GBM were lower than that of metastatic tumors. On perfusion MRI, the maximum rCBV of the peritumoral region (rCBVP of GBM was higher than that of brain metastases (P < 0.001. Conclusion: The addition of diffusion and perfusion to the MRI protocol increases the accuracy of differentiation between GBM and solitary brain metastasis and should be considered routinely. Keywords: Diffusion MRI, Perfusion MRI, GBM, Solitary brain metastases

Hybrid Brain-Computer Interface Techniques for Improved Classification Accuracy and Increased Number of Commands: A Review.

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Hong, Keum-Shik; Khan, Muhammad Jawad

2017-01-01

In this article, non-invasive hybrid brain-computer interface (hBCI) technologies for improving classification accuracy and increasing the number of commands are reviewed. Hybridization combining more than two modalities is a new trend in brain imaging and prosthesis control. Electroencephalography (EEG), due to its easy use and fast temporal resolution, is most widely utilized in combination with other brain/non-brain signal acquisition modalities, for instance, functional near infrared spectroscopy (fNIRS), electromyography (EMG), electrooculography (EOG), and eye tracker. Three main purposes of hybridization are to increase the number of control commands, improve classification accuracy and reduce the signal detection time. Currently, such combinations of EEG + fNIRS and EEG + EOG are most commonly employed. Four principal components (i.e., hardware, paradigm, classifiers, and features) relevant to accuracy improvement are discussed. In the case of brain signals, motor imagination/movement tasks are combined with cognitive tasks to increase active brain-computer interface (BCI) accuracy. Active and reactive tasks sometimes are combined: motor imagination with steady-state evoked visual potentials (SSVEP) and motor imagination with P300. In the case of reactive tasks, SSVEP is most widely combined with P300 to increase the number of commands. Passive BCIs, however, are rare. After discussing the hardware and strategies involved in the development of hBCI, the second part examines the approaches used to increase the number of control commands and to enhance classification accuracy. The future prospects and the extension of hBCI in real-time applications for daily life scenarios are provided.

Mobile Phone Chips Reduce Increases in EEG Brain Activity Induced by Mobile Phone-Emitted Electromagnetic Fields

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Henz, Diana; Schöllhorn, Wolfgang I.; Poeggeler, Burkhard

2018-01-01

Recent neurophysiological studies indicate that exposure to electromagnetic fields (EMFs) generated by mobile phone radiation can exert effects on brain activity. One technical solution to reduce effects of EMFs in mobile phone use is provided in mobile phone chips that are applied to mobile phones or attached to their surfaces. To date, there are no systematical studies on the effects of mobile phone chip application on brain activity and the underlying neural mechanisms. The present study investigated whether mobile phone chips that are applied to mobile phones reduce effects of EMFs emitted by mobile phone radiation on electroencephalographic (EEG) brain activity in a laboratory study. Thirty participants volunteered in the present study. Experimental conditions (mobile phone chip, placebo chip, no chip) were set up in a randomized within-subjects design. Spontaneous EEG was recorded before and after mobile phone exposure for two 2-min sequences at resting conditions. During mobile phone exposure, spontaneous EEG was recorded for 30 min during resting conditions, and 5 min during performance of an attention test (d2-R). Results showed increased activity in the theta, alpha, beta and gamma bands during EMF exposure in the placebo and no chip conditions. Application of the mobile phone chip reduced effects of EMFs on EEG brain activity and attentional performance significantly. Attentional performance level was maintained regarding number of edited characters. Further, a dipole analysis revealed different underlying activation patterns in the chip condition compared to the placebo chip and no chip conditions. Finally, a correlational analysis for the EEG frequency bands and electromagnetic high-frequency (HF) emission showed significant correlations in the placebo chip and no chip condition for the theta, alpha, beta, and gamma bands. In the chip condition, a significant correlation of HF with the theta and alpha bands, but not with the beta and gamma bands was

Mobile Phone Chips Reduce Increases in EEG Brain Activity Induced by Mobile Phone-Emitted Electromagnetic Fields.

Science.gov (United States)

Henz, Diana; Schöllhorn, Wolfgang I; Poeggeler, Burkhard

2018-01-01

Recent neurophysiological studies indicate that exposure to electromagnetic fields (EMFs) generated by mobile phone radiation can exert effects on brain activity. One technical solution to reduce effects of EMFs in mobile phone use is provided in mobile phone chips that are applied to mobile phones or attached to their surfaces. To date, there are no systematical studies on the effects of mobile phone chip application on brain activity and the underlying neural mechanisms. The present study investigated whether mobile phone chips that are applied to mobile phones reduce effects of EMFs emitted by mobile phone radiation on electroencephalographic (EEG) brain activity in a laboratory study. Thirty participants volunteered in the present study. Experimental conditions (mobile phone chip, placebo chip, no chip) were set up in a randomized within-subjects design. Spontaneous EEG was recorded before and after mobile phone exposure for two 2-min sequences at resting conditions. During mobile phone exposure, spontaneous EEG was recorded for 30 min during resting conditions, and 5 min during performance of an attention test (d2-R). Results showed increased activity in the theta, alpha, beta and gamma bands during EMF exposure in the placebo and no chip conditions. Application of the mobile phone chip reduced effects of EMFs on EEG brain activity and attentional performance significantly. Attentional performance level was maintained regarding number of edited characters. Further, a dipole analysis revealed different underlying activation patterns in the chip condition compared to the placebo chip and no chip conditions. Finally, a correlational analysis for the EEG frequency bands and electromagnetic high-frequency (HF) emission showed significant correlations in the placebo chip and no chip condition for the theta, alpha, beta, and gamma bands. In the chip condition, a significant correlation of HF with the theta and alpha bands, but not with the beta and gamma bands was

Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood.

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Parker, Matthew O; Evans, Alexandra M-D; Brock, Alistair J; Combe, Fraser J; Teh, Muy-Teck; Brennan, Caroline H

2016-01-01

Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and μ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning. © 2014 Society for the Study of Addiction.

THE EFFECT OF BETA GLUCAN OF SACCHAROMYCES CEREVISAE ON THE INCREASE OF THE NUMBER OF BRAIN CELLS IN SUBSTANTIA NIGRA BRAIN OF PARKINSON’S WISTAR STRAIN RAT (RATTUS NORVEGICUS MODEL INDUCED WITH ROTENONE

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Masruroh Rahayu

2015-01-01

Full Text Available ackground and aims. One of many neurodegenerative diseases afflicting the elderly is Parkinson. Beta glucan from Saccharomyces cerevisae is very potential to be used as a regenerative therapy of Parkinson's disease. Beta glucan can increase the mobilization of hematopoietic stem cells (HSCs from the bone marrow into the damaged tissues. Hematopoietic stem cells (HSCs which have been mobilized can regenerate and differentiate into brain cells so that the symptoms of Parkinson would be reduced. This research aims to find out the effects of the addition of Saccharomyces cerevisae toward the number of brain cells in substantia nigra Parkinson’s rat model. Method. The research was experimental in vivo using the draft of randomized post test only controlled group design. There were five groups that become the sample in this research with 5 rats for each group, i.e. negative control group, positive control group, Treatment Group 1, 2 and 3 (Rotenone + Saccharomyces cerevisae 18 mg/kgBB, 36 mg/kgBB, 72 mg/kgBBfor 4 weeks. Variable measured in this study was the number of brain cells in substantia nigra. The results of this study showed that Treatment Group 3 (72 mg/kgBB was a group with the largest number of brain cells than the other treatment groups. Statistical data obtained showed that the average number of brain cells in negative control group was 192.00 cells; positive control amounted to 116.80 cells; Treatment 1 amounted to 135.40 cells; Treatment 2 amounted to 140.80 cells; and Treatment 3 amounted to 161.80 cells. Result. The result of ANOVA test showed a significant difference between groups (p< 0.05, while the correlation test result indicated a strong correlation between the dose of Saccharomyces cerevisae and the number of substantia nigra of rat’s brain cells (r = 0,818. Conclusion. From this research, it can be concluded that the addition of Saccharomyces cerevisae with a dose of 18mg/kgBB, 36mg/kgBBdan 72 mg/kgBB is able to increase

Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats.

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Teodorak, Brena P; Ferreira, Gabriela K; Scaini, Giselli; Wessler, Letícia B; Heylmann, Alexandra S; Deroza, Pedro; Valvassori, Samira S; Zugno, Alexandra I; Quevedo, João; Streck, Emilio L

2015-08-01

Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute administration of fenproporex on acetylcholinesterase activity in brain of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5 or 25mg/kg i.p.) or vehicle (2% Tween 80). Two hours after the injection, the rats were killed by decapitation and the brain was removed for evaluation of acetylcholinesterase activity. Results showed that fenproporex administration increased acetylcholinesterase activity in the hippocampus and posterior cortex, whereas in the prefrontal cortex, striatum and cerebellum the enzyme activity was not altered. In conclusion, in the present study we demonstrated that acute administration of fenproporex exerts an effect in the cholinergic system causing an increase in the activity of acetylcholinesterase in a dose-dependent manner in the hippocampus and posterior cortex. Thus, we suggest that the imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines such as fenproporex.

Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats

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BRENA P. TEODORAK

2015-08-01

Full Text Available Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute administration of fenproporex on acetylcholinesterase activity in brain of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5 or 25mg/kg i.p. or vehicle (2% Tween 80. Two hours after the injection, the rats were killed by decapitation and the brain was removed for evaluation of acetylcholinesterase activity. Results showed that fenproporex administration increased acetylcholinesterase activity in the hippocampus and posterior cortex, whereas in the prefrontal cortex, striatum and cerebellum the enzyme activity was not altered. In conclusion, in the present study we demonstrated that acute administration of fenproporex exerts an effect in the cholinergic system causing an increase in the activity of acetylcholinesterase in a dose-dependent manner in the hippocampus and posterior cortex. Thus, we suggest that the imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines such as fenproporex.

Dynamic glucose enhanced (DGE) MRI for combined imaging of blood-brain barrier break down and increased blood volume in brain cancer.

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Xu, Xiang; Chan, Kannie W Y; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T; van Zijl, Peter C M

2015-12-01

Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared with contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (P blood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. © 2015 Wiley Periodicals, Inc.

Dynamic Glucose Enhanced (DGE) MRI for Combined Imaging of Blood Brain Barrier Break Down and Increased Blood Volume in Brain Cancer

Science.gov (United States)

Xu, Xiang; Chan, Kannie WY; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T.; van Zijl, Peter C.M.

2015-01-01

Purpose Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Methods Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. Results DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared to contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (pblood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. PMID:26404120

Increased frontal functional networks in adult survivors of childhood brain tumors

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Hongbo Chen

2016-01-01

Full Text Available Childhood brain tumors and associated treatment have been shown to affect brain development and cognitive outcomes. Understanding the functional connectivity of brain many years after diagnosis and treatment may inform the development of interventions to improve the long-term outcomes of adult survivors of childhood brain tumors. This work investigated the frontal region functional connectivity of 16 adult survivors of childhood cerebellar tumors after an average of 14.9 years from diagnosis and 16 demographically-matched controls using resting state functional MRI (rs-fMRI. Independent component analysis (ICA was applied to identify the resting state activity from rs-fMRI data and to select the specific regions associated with executive functions, followed by the secondary analysis of the functional networks connecting these regions. It was found that survivors exhibited differences in the functional connectivity in executive control network (ECN, default mode network (DMN and salience network (SN compared to demographically-matched controls. More specifically, the number of functional connectivity observed in the survivors is higher than that in the controls, and with increased strength, or stronger correlation coefficient between paired seeds, in survivors compared to the controls. Observed hyperconnectivity in the selected frontal functional network thus is consistent with findings in patients with other neurological injuries and diseases.

The Significance of Brain Transcranial Sonography in Burning Mouth Syndrome: a Pilot Study.

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Zavoreo, Iris; Vučićević, Vanja; Boras; Zadravec, Dijana; Bašić, Vanja; Kes; Ciliga, Dubravka; Gabrić, Dragana

2017-03-01

Burning mouth syndrome (BMS) is a chronic disorder which is affecting mostly postmenopausal women and is characterized by burning symptoms in the oral cavity on the clinically healthy oral mucosa. Also, the results of previous studies suggested a possible role of peripheral and/or central neurological disturbances in these patients. The aim of this study was to analyze patients with burning mouth syndrome using transcranial sonography. By use of transcranial sonography of the brain parenchyma, substantia nigra , midbrain raphe and brain nucleus were evaluated in 20 patients with BMS (64.7±12.3 years) and 20 controls with chronic pain in the lumbosacral region (61.5±15). Statistical analysis was performed by use of Student t test with significance set at pburning mouth syndrome might reflect central disturbances within this syndrome. Burning Mouth Syndrome; Transcranial Sonography; substantia nigra; Midbrain Raphe Nuclei; Red Nucleus.

Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke

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Valérie Wolff

2015-01-01

Full Text Available Cannabis has potential therapeutic use but tetrahydrocannabinol (THC, its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities Vmax (complexes I, III, and IV activities, Vsucc (complexes II, III, and IV activities, Vtmpd (complex IV activity, together with mitochondrial coupling (Vmax/V0, were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2 production, measured with Amplex Red. THC significantly decreased Vmax (−71%; P<0.0001, Vsucc (−65%; P<0.0001, and Vtmpd (−3.5%; P<0.001. Mitochondrial coupling (Vmax/V0 was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P<0.001. Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P<0.05 and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P<0.001. Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient’s vulnerability to stroke.

Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

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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.)

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.)

Near-infrared spectroscopy can reveal increases in brain activity related to animal-assisted therapy.

Science.gov (United States)

Morita, Yuka; Ebara, Fumio; Morita, Yoshimitsu; Horikawa, Etsuo

2017-08-01

[Purpose] Previous studies have indicated that animal-assisted therapy can promote recovery of psychological, social, and physiological function in mental disorders. This study was designed as a pilot evaluation of the use of near-infrared spectroscopy to objectively identify changes in brain activity that could mediate the effect of animal-assisted therapy. [Subjects and Methods] The participants were 20 healthy students (10 males and 10 females; age 19-21 years) of the Faculty of Agriculture, Saga University. Participants were shown a picture of a Tokara goat or shack (control) while prefrontal cortical oxygenated haemoglobin levels (representing neural activity) were measured by near-infrared spectroscopy. [Results] The prefrontal cortical near-infrared spectroscopy signal was significantly higher during viewing of the animal picture than during a rest condition or during viewing of the control picture. [Conclusion] Our results suggest that near-infrared spectroscopy can be used to objectively identify brain activity changes during human mentation regarding animals; furthermore, these preliminary results suggest the efficacy of animal-assisted therapy could be related to increased activation of the prefrontal cortex.

Platelet activating factor induces transient blood-brain barrier opening to facilitate edaravone penetration into the brain.

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Fang, Weirong; Zhang, Rui; Sha, Lan; Lv, Peng; Shang, Erxin; Han, Dan; Wei, Jie; Geng, Xiaohan; Yang, Qichuan; Li, Yunman

2014-03-01

The blood-brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6 h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra-performance liquid chromatograph combined with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1 μM PAF for 1 h significantly increased monolayer permeability to (125)I-albumin, which recovered 1 h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1 h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule-1, matrix-metalloproteinase-9 and P-glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain. Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into

Regulation of brain copper homeostasis by the brain barrier systems: Effects of Fe-overload and Fe-deficiency

International Nuclear Information System (INIS)

Monnot, Andrew D.; Behl, Mamta; Ho, Sanna; Zheng, Wei

2011-01-01

Maintaining brain Cu homeostasis is vital for normal brain function. The role of systemic Fe deficiency (FeD) or overload (FeO) due to metabolic diseases or environmental insults in Cu homeostasis in the cerebrospinal fluid (CSF) and brain tissues remains unknown. This study was designed to investigate how blood-brain barrier (BBB) and blood-SCF barrier (BCB) regulated Cu transport and how FeO or FeD altered brain Cu homeostasis. Rats received an Fe-enriched or Fe-depleted diet for 4 weeks. FeD and FeO treatment resulted in a significant increase (+ 55%) and decrease (− 56%) in CSF Cu levels (p < 0.05), respectively; however, neither treatment had any effect on CSF Fe levels. The FeD, but not FeO, led to significant increases in Cu levels in brain parenchyma and the choroid plexus. In situ brain perfusion studies demonstrated that the rate of Cu transport into the brain parenchyma was significantly faster in FeD rats (+ 92%) and significantly slower (− 53%) in FeO rats than in controls. In vitro two chamber Transwell transepithelial transport studies using primary choroidal epithelial cells revealed a predominant efflux of Cu from the CSF to blood compartment by the BCB. Further ventriculo-cisternal perfusion studies showed that Cu clearance by the choroid plexus in FeD animals was significantly greater than control (p < 0.05). Taken together, our results demonstrate that both the BBB and BCB contribute to maintain a stable Cu homeostasis in the brain and CSF. Cu appears to enter the brain primarily via the BBB and is subsequently removed from the CSF by the BCB. FeD has a more profound effect on brain Cu levels than FeO. FeD increases Cu transport at the brain barriers and prompts Cu overload in the CNS. The BCB plays a key role in removing the excess Cu from the CSF.

Regulation of brain copper homeostasis by the brain barrier systems: Effects of Fe-overload and Fe-deficiency

Energy Technology Data Exchange (ETDEWEB)

Monnot, Andrew D.; Behl, Mamta; Ho, Sanna; Zheng, Wei, E-mail: wzheng@purdue.edu

2011-11-15

Maintaining brain Cu homeostasis is vital for normal brain function. The role of systemic Fe deficiency (FeD) or overload (FeO) due to metabolic diseases or environmental insults in Cu homeostasis in the cerebrospinal fluid (CSF) and brain tissues remains unknown. This study was designed to investigate how blood-brain barrier (BBB) and blood-SCF barrier (BCB) regulated Cu transport and how FeO or FeD altered brain Cu homeostasis. Rats received an Fe-enriched or Fe-depleted diet for 4 weeks. FeD and FeO treatment resulted in a significant increase (+ 55%) and decrease (- 56%) in CSF Cu levels (p < 0.05), respectively; however, neither treatment had any effect on CSF Fe levels. The FeD, but not FeO, led to significant increases in Cu levels in brain parenchyma and the choroid plexus. In situ brain perfusion studies demonstrated that the rate of Cu transport into the brain parenchyma was significantly faster in FeD rats (+ 92%) and significantly slower (- 53%) in FeO rats than in controls. In vitro two chamber Transwell transepithelial transport studies using primary choroidal epithelial cells revealed a predominant efflux of Cu from the CSF to blood compartment by the BCB. Further ventriculo-cisternal perfusion studies showed that Cu clearance by the choroid plexus in FeD animals was significantly greater than control (p < 0.05). Taken together, our results demonstrate that both the BBB and BCB contribute to maintain a stable Cu homeostasis in the brain and CSF. Cu appears to enter the brain primarily via the BBB and is subsequently removed from the CSF by the BCB. FeD has a more profound effect on brain Cu levels than FeO. FeD increases Cu transport at the brain barriers and prompts Cu overload in the CNS. The BCB plays a key role in removing the excess Cu from the CSF.

Brain mitochondria from DJ-1 knockout mice show increased respiration-dependent hydrogen peroxide consumption

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Pamela Lopert

2014-01-01

Full Text Available Mutations in the DJ-1 gene have been shown to cause a rare autosomal-recessive genetic form of Parkinson’s disease (PD. The function of DJ-1 and its role in PD development has been linked to multiple pathways, however its exact role in the development of PD has remained elusive. It is thought that DJ-1 may play a role in regulating reactive oxygen species (ROS formation and overall oxidative stress in cells through directly scavenging ROS itself, or through the regulation of ROS scavenging systems such as glutathione (GSH or thioredoxin (Trx or ROS producing complexes such as complex I of the electron transport chain. Previous work in this laboratory has demonstrated that isolated brain mitochondria consume H2O2 predominantly by the Trx/Thioredoxin Reductase (TrxR/Peroxiredoxin (Prx system in a respiration dependent manner (Drechsel et al., Journal of Biological Chemistry, 2010. Therefore we wanted to determine if mitochondrial H2O2 consumption was altered in brains from DJ-1 deficient mice (DJ-1−/−. Surprisingly, DJ-1−/− mice showed an increase in mitochondrial respiration-dependent H2O2 consumption compared to controls. To determine the basis of the increased H2O2 consumption in DJ1−/− mice, the activities of Trx, Thioredoxin Reductase (TrxR, GSH, glutathione disulfide (GSSG and glutathione reductase (GR were measured. Compared to control mice, brains from DJ-1−/− mice showed an increase in (1 mitochondrial Trx activity, (2 GSH and GSSG levels and (3 mitochondrial glutaredoxin (GRX activity. Brains from DJ-1−/− mice showed a decrease in mitochondrial GR activity compared to controls. The increase in the enzymatic activities of mitochondrial Trx and total GSH levels may account for the increased H2O2 consumption observed in the brain mitochondria in DJ-1−/− mice perhaps as an adaptive response to chronic DJ-1 deficiency.

Brain size and urbanization in birds

Institute of Scientific and Technical Information of China (English)

Anders; Pape; M?ller; Johannes; Erritz?e

2015-01-01

Background: Brain size may affect the probability of invasion of urban habitats if a relatively larger brain entails superior ability to adapt to novel environments. However, once urbanized urban environments may provide poor quality food that has negative consequences for normal brain development resulting in an excess of individuals with small brains.Methods: Here we analyze the independent effects of mean, standard deviation and skewness in brain mass for invasion of urban habitats by 108 species of birds using phylogenetic multiple regression analyses weighted by sample size.Results: There was no significant difference in mean brain mass between urbanized and non-urbanized species or between urban and rural populations of the same species, and mean brain mass was not significantly correlated with time since urbanization. Bird species that became urbanized had a greater standard deviation in brain mass than non-urbanized species, and the standard deviation in brain mass increased with time since urbanization. Brain mass was significantly left skewed in species that remained rural, while there was no significant skew in urbanized species. The degree of left skew was greater in urban than in rural populations of the same species, and successfully urbanized species decreased the degree of left skew with time since urbanization. This is consistent with the hypothesis that sub-optimal brain development was more common in rural habitats resulting in disproportionately many individuals with very smal brains.Conclusions: These findings do not support the hypothesis that large brains promote urbanization, but suggest that skewness has played a role in the initial invasion of urban habitats, and that variance and skew in brain mass have increased as species have become urbanized.

Brain size and urbanization in birds

Institute of Scientific and Technical Information of China (English)

Anders Pape Mller; Johannes Erritze

2015-01-01

Background:Brain size may affect the probability of invasion of urban habitats if a relatively larger brain entails superior ability to adapt to novel environments. However, once urbanized urban environments may provide poor quality food that has negative consequences for normal brain development resulting in an excess of individuals with small brains. Methods:Here we analyze the independent effects of mean, standard deviation and skewness in brain mass for invasion of urban habitats by 108 species of birds using phylogenetic multiple regression analyses weighted by sample size. Results:There was no significant difference in mean brain mass between urbanized and non-urbanized species or between urban and rural populations of the same species, and mean brain mass was not significantly correlated with time since urbanization. Bird species that became urbanized had a greater standard deviation in brain mass than non-urbanized species, and the standard deviation in brain mass increased with time since urbanization. Brain mass was significantly left skewed in species that remained rural, while there was no significant skew in urbanized species. The degree of left skew was greater in urban than in rural populations of the same species, and successfully urbanized species decreased the degree of left skew with time since urbanization. This is consistent with the hypothesis that sub-optimal brain development was more common in rural habitats resulting in disproportionately many individuals with very smal brains. Conclusions:These findings do not support the hypothesis that large brains promote urbanization, but suggest that skewness has played a role in the initial invasion of urban habitats, and that variance and skew in brain mass have increased as species have become urbanized.

Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures

DEFF Research Database (Denmark)

Penkowa, M; Molinero, A; Carrasco, J

2001-01-01

and were killed six days later. Morphological damage to the hippocampal field CA1-CA3 was seen after kainic acid treatment. Reactive astrogliosis and microgliosis were prominent in kainic acid-injected normal mice hippocampus, and clear signs of increased oxidative stress were evident. Thus......The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mice......, and caused a significant mortality (62%) only in the latter mice, indicating that interleukin-6 deficiency increased the susceptibility to kainic acid-induced brain damage. To compare the histopathological damage caused to the brain, control and interleukin-6 null mice were administered 8.75mg/kg kainic acid...

Glycolysis and the significance of lactate in traumatic brain injury

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Keri Linda Carpenter

2015-04-01

Full Text Available In traumatic brain injury (TBI patients, elevation of the brain extracellular lactate concentration and the lactate/pyruvate ratio are well recognised, and are associated statistically with unfavourable clinical outcome. Brain extracellular lactate was conventionally regarded as a waste product of glucose, when glucose is metabolised via glycolysis (Embden-Meyerhof-Parnas pathway to pyruvate, followed by conversion to lactate by the action of lactate dehydrogenase, and export of lactate into the extracellular fluid. In TBI, glycolytic lactate is ascribed to hypoxia or mitochondrial dysfunction, although the precise nature of the latter is incompletely understood. Seemingly in contrast to lactate’s association with unfavourable outcome is a growing body of evidence that lactate can be beneficial. The idea that the brain can utilise lactate by feeding into the tricarboxylic acid (TCA cycle of neurons, first published two decades ago, has become known as the astrocyte-neuron lactate shuttle hypothesis. Direct evidence of brain utilisation of lactate was first obtained 5 years ago in a cerebral microdialysis study in TBI patients, where administration of 13C-labelled lactate via the microdialysis catheter and simultaneous collection of the emerging microdialysates, with 13C NMR analysis, revealed 13C labelling in glutamine consistent with lactate utilisation via the TCA cycle. This suggests that where neurons are too damaged to utilise the lactate produced from glucose by astrocytes, i.e. uncoupling of neuronal and glial metabolism, high extracellular levels of lactate would accumulate, explaining association between high lactate and poor outcome. An intravenous exogenous lactate supplementation study in TBI patients showed evidence for a beneficial effect judged by surrogate endpoints. Here we review current knowledge about glycolysis and lactate in TBI, how it can be measured in patients, and whether it can be modulated to achieve better

Increased brain-predicted aging in treated HIV disease

NARCIS (Netherlands)

Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J; Kalsbeek, A.

OBJECTIVE: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. METHODS: A

Increased brain-predicted aging in treated HIV disease

NARCIS (Netherlands)

Cole, James H.; Underwood, Jonathan; Caan, Matthan W. A.; de Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W. N. M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B. L. M.; Winston, Alan; Reiss, Peter; Sharp, David J.; Schouten, J.; Kooij, K. W.; Elsenga, B. C.; Janssen, F. R.; Heidenrijk, M.; Schrijver, J. H. N.; Zikkenheiner, W.; van der Valk, M.; Henderiks, A.; Kootstra, N. A.; Harskamp-Holwerda, A. M.; Maurer, I.; Ruiz, M. M. Mangas; Booiman, T.; Girigorie, A. F.; Villaudy, J.; Frankin, E.; Pasternak, A.; Berkhout, B.; van der Kuyl, T.; Stege, J. A. ter; Twennaar, M. Klein; Su, T.; Siteur-van Rijnstra, E.; Weijer, K.; Bisschop, P. H. L. T.; Kalsbeek, A.; Wezel, M.; Visser, I.; Ruhé , H. G.; Tembo, L.; Stott, M.; Prins, M. [= Maria

2017-01-01

To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. A large sample of

Rats exposed to 2.45GHz of non-ionizing radiation exhibit behavioral changes with increased brain expression of apoptotic caspase 3.

Science.gov (United States)

Varghese, Rini; Majumdar, Anuradha; Kumar, Girish; Shukla, Amit

2018-03-01

In recent years there has been a tremendous increase in use of Wi-Fi devices along with mobile phones, globally. Wi-Fi devices make use of 2.4GHz frequency. The present study evaluated the impact of 2.45GHz radiation exposure for 4h/day for 45days on behavioral and oxidative stress parameters in female Sprague Dawley rats. Behavioral tests of anxiety, learning and memory were started from day 38. Oxidative stress parameters were estimated in brain homogenates after sacrificing the rats on day 45. In morris water maze, elevated plus maze and light dark box test, the 2.45GHz radiation exposed rats elicited memory decline and anxiety behavior. Exposure decreased activities of super oxide dismutase, catalase and reduced glutathione levels whereas increased levels of brain lipid peroxidation was encountered in the radiation exposed rats, showing compromised anti-oxidant defense. Expression of caspase 3 gene in brain samples were quantified which unraveled notable increase in the apoptotic marker caspase 3 in 2.45GHz radiation exposed group as compared to sham exposed group. No significant changes were observed in histopathological examinations and brain levels of TNF-α. Analysis of dendritic arborization of neurons showcased reduction in number of dendritic branching and intersections which corresponds to alteration in dendritic structure of neurons, affecting neuronal signaling. The study clearly indicates that exposure of rats to microwave radiation of 2.45GHz leads to detrimental changes in brain leading to lowering of learning and memory and expression of anxiety behavior in rats along with fall in brain antioxidant enzyme systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Carbogen inhalation increases oxygen transport to hypoperfused brain tissue in patients with occlusive carotid artery disease: increased oxygen transport to hypoperfused brain

DEFF Research Database (Denmark)

Ashkanian, Mahmoud; Gjedde, Albert; Mouridsen, Kim

2009-01-01

to inhaled oxygen (the mixture known as carbogen). In the present study, we measured CBF by positron emission tomography (PET) during inhalation of test gases (O(2), carbogen, and atmospheric air) in healthy volunteers (n = 10) and in patients with occlusive carotid artery disease (n = 6). Statistical...... and Sa(O2) are readily obtained with carbogen, while oxygen increases only Sa(O2). Thus, carbogen improves oxygen transport to brain tissue more efficiently than oxygen alone. Further studies with more subjects are, however, needed to investigate the applicability of carbogen for long-term inhalation...

Brain atrophy during aging

International Nuclear Information System (INIS)

Matsuzawa, Taiju; Takeda, Shumpei; Hatazawa, Jun

1985-01-01

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

Maternal obesity increases inflammation and exacerbates damage following neonatal hypoxic-ischaemic brain injury in rats.

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Teo, Jonathan D; Morris, Margaret J; Jones, Nicole M

2017-07-01

In humans, maternal obesity is associated with an increase in the incidence of birth related difficulties. However, the impact of maternal obesity on the severity of brain injury in offspring is not known. Recent studies have found evidence of increased glial response and inflammatory mediators in the brains as a result of obesity in humans and rodents. We hypothesised that hypoxic-ischaemic (HI) brain injury is greater in neonatal offspring from obese rat mothers compared to lean controls. Female Sprague Dawley rats were randomly allocated to high fat (HFD, n=8) or chow (n=4) diet and mated with lean male rats. On postnatal day 7 (P7), male and female pups were randomly assigned to HI injury or control (C) groups. HI injury was induced by occlusion of the right carotid artery followed by 3h exposure to 8% oxygen, at 37°C. Control pups were removed from the mother for the same duration under ambient conditions. Righting behaviour was measured on day 1 and 7 following HI. The extent of brain injury was quantified in brain sections from P14 pups using cresyl violet staining and the difference in volume between brain hemispheres was measured. Before mating, HFD mothers were 11% heavier than Chow mothers (pmaternal weight. Similar observations were made with neuronal staining showing a greater loss of neurons in the brain of offspring from HFD-mothers following HI compared to Chow. Astrocytes appeared to more hypertrophic and a greater number of microglia were present in the injured hemisphere in offspring from mothers on HFD. HI caused an increase in the proportion of amoeboid microglia and exposure to maternal HFD exacerbated this response. In the contralateral hemisphere, offspring exposed to maternal HFD displayed a reduced proportion of ramified microglia. Our data clearly demonstrate that maternal obesity can exacerbate the severity of brain damage caused by HI in neonatal offspring. Given that previous studies have shown enhanced inflammatory responses in

Increased brain fatty acid uptake in metabolic syndrome

DEFF Research Database (Denmark)

Karmi, Anna; Iozzo, Patricia; Viljanen, Antti

2010-01-01

To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.......To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it....

Increased cerebral (R-[11C]PK11195 uptake and glutamate release in a rat model of traumatic brain injury: a longitudinal pilot study

Directory of Open Access Journals (Sweden)

Lammertsma Adriaan A

2011-06-01

Full Text Available Abstract Background The aim of the present study was to investigate microglia activation over time following traumatic brain injury (TBI and to relate these findings to glutamate release. Procedures Sequential dynamic (R-[11C]PK11195 PET scans were performed in rats 24 hours before (baseline, and one and ten days after TBI using controlled cortical impact, or a sham procedure. Extracellular fluid (ECF glutamate concentrations were measured using cerebral microdialysis. Brains were processed for histopathology and (immuno-histochemistry. Results Ten days after TBI, (R-[11C]PK11195 binding was significantly increased in TBI rats compared with both baseline values and sham controls (p -1 as compared with the sham procedure (6.4 ± 3.6 μmol·L-1. Significant differences were found between TBI and sham for ED-1, OX-6, GFAP, Perl's, and Fluoro-Jade B. Conclusions Increased cerebral uptake of (R-[11C]PK11195 ten days after TBI points to prolonged and ongoing activation of microglia. This activation followed a significant acute posttraumatic increase in ECF glutamate levels.

Acute supramaximal exercise increases the brain oxygenation in relation to cognitive workload

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Cem Seref Bediz

2016-04-01

Full Text Available Single bout of exercise can improve the performance on cognitive tasks. However, cognitive responses may be controversial due to different type, intensity, and duration of exercise. In addition, the mechanism of the effect of acute exercise on brain is still unclear. This study was aimed to investigate the effects of supramaximal exercise on cognitive tasks by means of brain oxygenation monitoring. The brain oxygenation of Prefrontal cortex (PFC was measured on 35 healthy male volunteers via functional Near Infrared Spectroscopy (fNIRS system. Subjects performed 2-Back test before and after the supramaximal exercise (Wingate Anaerobic Test lasting 30-s on cycle ergometer. The PFC oxygenation change evaluation revealed that PFC oxygenation rise during post-exercise 2-Back task was considerably higher than those in pre-exercise 2-Back task. In order to describe the relationship between oxygenation change and exercise performance, subjects were divided into two groups as high performers (HP and low performers (LP according to their peak power values (PP obtained from the supramaximal test. The oxy-hemoglobin (oxy-Hb values were compared between pre- and post-exercise conditions within subjects and also between subjects according to peak power. When performers were compared, in the HP group, the oxy-Hb values in post-exercise 2-Back test were significantly higher than those in pre-exercise 2-Back test. HP had significantly higher post-exercise oxy-Hb change (Δ than those of LP. In addition, peak power values of the total group were significantly correlated with Δoxy-Hb. The key findings of the present study revealed that acute supramaximal exercise has an impact on the brain oxygenation during a cognitive task. Also, the higher the anaerobic PP describes the larger the oxy-Hb response in post-exercise cognitive task. The current study also demonstrated a significant correlation between peak power (exercise load and post-exercise hemodynamic

IL-6 deficiency leads to reduced metallothionein-I+II expression and increased oxidative stress in the brain stem after 6-aminonicotinamide treatment

DEFF Research Database (Denmark)

Penkowa, M; Hidalgo, J

2000-01-01

-AN-injected IL-6KO mice reactive astrocytosis and recruitment of macrophages and T-lymphocytes were clearly reduced, as were BM leukopoiesis and spleen immune reaction. Expression of MT-I+II was significantly reduced while MT-III was increased. Oxidative stress, as determined by measuring nitrated...... in brain stem gray matter areas and BM toxicity. In both normal and genetically IL-6-deficient mice (IL-6 knockout (IL-6KO) mice), the extent of astroglial degeneration/cell death in the brain stem was similar as determined from disappearance of GFAP immunoreactivity. In 6-AN-injected normal mice reactive...... tyrosine and malondialdehyde, was increased by 6-AN to a greater extent in IL-6KO mice. The blood-brain barrier to albumin was only disrupted in 6-AN-injected normal mice, which likely is due to the substantial migration of blood-derived inflammatory cells into the CNS. The present results demonstrate...

Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain.

Science.gov (United States)

Lin, Ai-Ling; Zhang, Wei; Gao, Xiaoli; Watts, Lora

2015-07-01

Caloric restriction (CR) has been shown to increase the life span and health span of a broad range of species. However, CR effects on in vivo brain functions are far from explored. In this study, we used multimetric neuroimaging methods to characterize the CR-induced changes of brain metabolic and vascular functions in aging rats. We found that old rats (24 months of age) with CR diet had reduced glucose uptake and lactate concentration, but increased ketone bodies level, compared with the age-matched and young (5 months of age) controls. The shifted metabolism was associated with preserved vascular function: old CR rats also had maintained cerebral blood flow relative to the age-matched controls. When investigating the metabolites in mitochondrial tricarboxylic acid cycle, we found that citrate and α-ketoglutarate were preserved in the old CR rats. We suggest that CR is neuroprotective; ketone bodies, cerebral blood flow, and α-ketoglutarate may play important roles in preserving brain physiology in aging. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke.

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Orbe, J; Alexandru, N; Roncal, C; Belzunce, M; Bibiot, P; Rodriguez, J A; Meijers, J C M; Georgescu, A; Paramo, J A

2015-08-01

Thrombin-activatable fibrinolysis inhibitor (TAFI) plays an important role in coagulation and fibrinolysis. Whereas TAFI deficiency may lead to a haemorrhagic tendency, data from TAFI knockout mice (TAFI-/-) are controversial and no differences have been reported in these animals after ischemic stroke. There are also no data regarding the role of circulating microparticles (MPs) in TAFI-/-. to examine the effect of tPA on the rate of intracranial haemorrhage (ICH) and on MPs generated in a model of ischemic stroke in TAFI-/- mice. Thrombin was injected into the middle cerebral artery (MCA) to analyse the effect of tPA (10mg/Kg) on the infarct size and haemorrhage in the absence of TAFI. Immunofluorescence for Fluoro-Jade C was performed on frozen brain slides to analyse neuronal degeneration after ischemia. MPs were isolated from mouse blood and their concentrations calculated by flow cytometry. Compared with saline, tPA significantly increased the infarct size in TAFI-/- mice (p<0.05). Although plasma fibrinolytic activity (fibrin plate assay) was higher in these animals, no macroscopic or microscopic ICH was detected. A positive signal for apoptosis and degenerating neurons was observed in the infarct area, being significantly higher in tPA treated TAFI-/- mice (p<0.05). Interestingly, higher numbers of MPs were found in TAFI-/- plasma as compared to wild type, after stroke (p<0.05). TAFI deficiency results in increased brain damage in a model of thrombolysis after ischemic stroke, which was not associated with bleeding but with neuronal degeneration and MP production. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aging leads to altered microglial function that reduces brain resiliency increasing vulnerability to neurodegenerative diseases.

Science.gov (United States)

Bickford, Paula C; Flowers, Antwoine; Grimmig, Bethany

2017-08-01

Aging is the primary risk factor for many neurodegenerative diseases. Thus, understanding the basic biological changes that take place with aging that lead to the brain being less resilient to disease progression of neurodegenerative diseases such as Parkinson's disease or Alzheimer's disease or insults to the brain such as stroke or traumatic brain injuries. Clearly this will not cure the disease per se, yet increasing the ability of the brain to respond to injury could improve long term outcomes. The focus of this review is examining changes in microglia with age and possible therapeutic interventions involving the use of polyphenol rich dietary supplements. Published by Elsevier Inc.

Cloning of a Gene Whose Expression is Increased in Scrapie and in Senile Plaques in Human Brain

Science.gov (United States)

Wietgrefe, S.; Zupancic, M.; Haase, A.; Chesebro, B.; Race, R.; Frey, W.; Rustan, T.; Friedman, R. L.

1985-12-01

A complementary DNA library was constructed from messenger RNA's extracted from the brains of mice infected with the scrapie agent. The library was differentially screened with the objectives of finding clones that might be used as markers of infection and finding clones of genes whose increased expression might be correlated with the pathological changes common to scrapie and Alzheimer's disease. A gene was identified whose expression is increased in scrapie. The complementary DNA corresponding to this gene hybridized preferentially and focally to cells in the brains of scrapie-infected animals. The cloned DNA also hybridized to the neuritic plaques found with increased frequency in brains of patients with Alzheimer's disease.

Human Traumatic Brain Injury Results in Oligodendrocyte Death and Increases the Number of Oligodendrocyte Progenitor Cells.

Science.gov (United States)

Flygt, Johanna; Gumucio, Astrid; Ingelsson, Martin; Skoglund, Karin; Holm, Jonatan; Alafuzoff, Irina; Marklund, Niklas

2016-06-01

Oligodendrocyte (OL) death may contribute to white matter pathology, a common cause of network dysfunction and persistent cognitive problems in patients with traumatic brain injury (TBI). Oligodendrocyte progenitor cells (OPCs) persist throughout the adult CNS and may replace dead OLs. OL death and OPCs were analyzed by immunohistochemistry of human brain tissue samples, surgically removed due to life-threatening contusions and/or focal brain swelling at 60.6 ± 75 hours (range 4-192 hours) postinjury in 10 severe TBI patients (age 51.7 ± 18.5 years). Control brain tissue was obtained postmortem from 5 age-matched patients without CNS disorders. TUNEL and CC1 co-labeling was used to analyze apoptotic OLs, which were increased in injured brain tissue (p The OPC markers Olig2, A2B5, NG2, and PDGFR-α were used. In contrast to the number of single-labeled Olig2, A2B5, NG2, and PDGFR-α-positive cells, numbers of Olig2 and A2B5 co-labeled cells were increased in TBI samples (p human TBI results in OL death and increases in OPCs postinjury, which may influence white matter function following TBI. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Experimental increase in brain HIPDM uptake by hypercapnia

International Nuclear Information System (INIS)

Karatzas, N.D.; Sfakianakis, G.N.; Pappas, D.; Duncan, R.; Heal, A.; Serafini, A.; Kung, H.F.

1988-01-01

The 30-min brain uptake of [ 125 I]HIPDM was measured in conscious rats--normocapnic (n = 8), hypercapnic (n = 12), and hyperoxic (n = 6). A mean 41.2% higher uptake was found in the brains of hypercapnic animals (p less than 0.01). In the three groups of rats, brain HIPDM uptake had a negative correlation with body weight (p less than 0.001) and a positive correlation with arterial pCO 2 (p less than 0.01), when adjusted for body weight. These results indicate that HIPDM uptake with hypercapnia may be used as a provocative test to measure cerebral blood flow reserves

Podoplanin expression in primary brain tumors induces platelet aggregation and increases risk of venous thromboembolism.

Science.gov (United States)

Riedl, Julia; Preusser, Matthias; Nazari, Pegah Mir Seyed; Posch, Florian; Panzer, Simon; Marosi, Christine; Birner, Peter; Thaler, Johannes; Brostjan, Christine; Lötsch, Daniela; Berger, Walter; Hainfellner, Johannes A; Pabinger, Ingrid; Ay, Cihan

2017-03-30

Venous thromboembolism (VTE) is common in patients with brain tumors, and underlying mechanisms are unclear. We hypothesized that podoplanin, a sialomucin-like glycoprotein, increases the risk of VTE in primary brain tumors via its ability to induce platelet aggregation. Immunohistochemical staining against podoplanin and intratumoral platelet aggregates was performed in brain tumor specimens of 213 patients (mostly high-grade gliomas [89%]) included in the Vienna Cancer and Thrombosis Study, a prospective observational cohort study of patients with newly diagnosed cancer or progressive disease aimed at identifying patients at risk of VTE. Platelet aggregation in response to primary human glioblastoma cells was investigated in vitro. During 2-year follow-up, 29 (13.6%) patients developed VTE. One-hundred fifty-one tumor specimens stained positive for podoplanin (33 high expression, 47 medium expression, 71 low expression). Patients with podoplanin-positive tumors had lower peripheral blood platelet counts ( P < .001) and higher D-dimer levels ( P < .001). Podoplanin staining intensity was associated with increasing levels of intravascular platelet aggregates in tumor specimens ( P < .001). High podoplanin expression was associated with an increased risk of VTE (hazard ratio for high vs no podoplanin expression: 5.71; 95% confidence interval, 1.52-21.26; P = 010), independent of age, sex, and tumor type. Podoplanin-positive primary glioblastoma cells induced aggregation of human platelets in vitro, which could be abrogated by an antipodoplanin antibody. In conclusion, high podoplanin expression in primary brain tumors induces platelet aggregation, correlates with hypercoagulability, and is associated with increased risk of VTE. Our data indicate novel insights into the pathogenesis of VTE in primary brain tumors. © 2017 by The American Society of Hematology.

Increasing Rates of Brain Tumours in the Swedish National Inpatient Register and the Causes of Death Register

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Lennart Hardell

2015-04-01

Full Text Available Radiofrequency emissions in the frequency range 30 kHz–300 GHz were evaluated to be Group 2B, i.e., “possibly”, carcinogenic to humans by the International Agency for Research on Cancer (IARC at WHO in May 2011. The Swedish Cancer Register has not shown increasing incidence of brain tumours in recent years and has been used to dismiss epidemiological evidence on a risk. In this study we used the Swedish National Inpatient Register (IPR and Causes of Death Register (CDR to further study the incidence comparing with the Cancer Register data for the time period 1998–2013 using joinpoint regression analysis. In the IPR we found a joinpoint in 2007 with Annual Percentage Change (APC +4.25%, 95% CI +1.98, +6.57% during 2007–2013 for tumours of unknown type in the brain or CNS. In the CDR joinpoint regression found one joinpoint in 2008 with APC during 2008–2013 +22.60%, 95% CI +9.68, +37.03%. These tumour diagnoses would be based on clinical examination, mainly CT and/or MRI, but without histopathology or cytology. No statistically significant increasing incidence was found in the Swedish Cancer Register during these years. We postulate that a large part of brain tumours of unknown type are never reported to the Cancer Register. Furthermore, the frequency of diagnosis based on autopsy has declined substantially due to a general decline of autopsies in Sweden adding further to missing cases. We conclude that the Swedish Cancer Register is not reliable to be used to dismiss results in epidemiological studies on the use of wireless phones and brain tumour risk.

When larger brains do not have more neurons: Increased numbers of cells are compensated by decreased average cell size across mouse individuals

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Suzana eHerculano-Houzel

2015-06-01

Full Text Available There is a strong trend toward increased brain size in mammalian evolution, with larger brains composed of more and larger neurons than smaller brains across species within each mammalian order. Does the evolution of increased numbers of brain neurons, and thus larger brain size, occur simply through the selection of individuals with more and larger neurons, and thus larger brains, within a population? That is, do individuals with larger brains also have more, and larger, neurons than individuals with smaller brains, such that allometric relationships across species are simply an extension of intraspecific scaling? Here we show that this is not the case across adult male mice of a similar age. Rather, increased numbers of neurons across individuals are accompanied by increased numbers of other cells and smaller average cell size of both types, in a trade-off that explains how increased brain mass does not necessarily ensue. Fundamental regulatory mechanisms thus must exist that tie numbers of neurons to numbers of other cells and to average cell size within individual brains. Finally, our results indicate that changes in brain size in evolution are not an extension of individual variation in numbers of neurons, but rather occur through step changes that must simultaneously increase numbers of neurons and cause cell size to increase, rather than decrease.

The significance of brain scintiscanning with Te-99m in the diagnosis of brain tumours

International Nuclear Information System (INIS)

Spengel, F.

1973-01-01

The author gives a short introduction to the technology and methods of brain scintiscanning and states his reasons for using the γ source 99 m Tc as test substance. The pathophysiological causes of the accumulation of this nuclide in tumour tissue are discussed, and the normal brain scan is illustrated by models. After this, the scintiscans with tu1our diagnosis obtained in the 2nd university clinic for internal diseases in the period between 1968 and 1970 are listed. 11 of these cases are treated in detail in a casuistics, and the findings are discussed. (orig.) [de

Physical Exercise Keeps the Brain Connected: Biking Increases White Matter Integrity in Patients With Schizophrenia and Healthy Controls.

Science.gov (United States)

Svatkova, Alena; Mandl, René C W; Scheewe, Thomas W; Cahn, Wiepke; Kahn, René S; Hulshoff Pol, Hilleke E

2015-07-01

It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We examined the effect of 6 months exercise on a stationary bicycle on the brain in patients with schizophrenia and healthy controls. Biking is an endemic skill in the Netherlands and thus offers an ideal situation to disentangle the effects of learning vs practice. The 33 participating patients with schizophrenia and 48 healthy individuals were assigned to either one of two conditions, ie, physical exercise or life-as-usual, balanced for diagnosis. Diffusion tensor imaging brain scans were made prior to and after intervention. We demonstrate that irrespective of diagnosis regular physical exercise of an overlearned skill, such as bicycling, significantly increases the integrity, especially of motor functioning related, white matter fiber tracts whereas life-as-usual leads to a decrease in fiber integrity. Our findings imply that exercise of an overlearned physical skill improves brain connectivity in patients and healthy individuals. This has important implications for understanding the effect of fitness programs on the brain in both healthy subjects and patients with schizophrenia. Moreover, the outcome may even apply to the nonphysical realm. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Increased brain water self-diffusion in patients with idiopathic intracranial hypertension

DEFF Research Database (Denmark)

Gideon, P; Sørensen, P S; Thomsen, C

1995-01-01

PURPOSE: To investigate changes in brain water diffusion in patients with idiopathic intracranial hypertension. METHODS: A motion-compensated MR pulse sequence was used to create diffusion maps of the apparent diffusion coefficient (ADC) in 12 patients fulfilling conventional diagnostic criteria...... for idiopathic intracranial hypertension and in 12 healthy volunteers. RESULTS: A significantly larger ADC was found within subcortical white matter in the patient group (mean, 1.16 x 10(-9) m2/s) than in the control group (mean, 0.75 x 10(-9) m2/s), whereas no significant differences were found within cortical...

Fatty acid amide hydrolase (FAAH) regulates hypercapnia/ischemia-induced increases in n-acylethanolamines in mouse brain.

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Lin, Lin; Metherel, Adam H; Jones, Peter J; Bazinet, Richard P

2017-09-01

N-acylethanolamines (NAEs) are endogenous lipid ligands for several receptors including cannabinoid receptors and peroxisome proliferator-activated receptor-alpha (PPAR-α), which regulate numerous physiological functions. Fatty acid amide hydrolase (FAAH) is largely responsible for the degradation of NAEs. However, at high concentrations of ethanolamines and unesterified fatty acids, FAAH can also catalyze the reverse reaction, producing NAEs. Several brain insults such as ischemia and hypoxia increase brain unesterified fatty acids. Because FAAH can catalyze the synthesis of NAE, we aimed to test whether FAAH was necessary for CO 2 -induced hypercapnia/ischemia increases in NAE. To test this, we examined levels of NAEs, 1- and 2-arachidonoylglycerols as well as their corresponding fatty acid precursors in wild-type and mice lacking FAAH (FAAH-KO) with three Kill methods: (i) head-focused, high-energy microwave irradiation (microwave), (ii) 5 min CO 2 followed by microwave irradiation (CO 2 + microwave), and (iii) 5 min CO 2 only (CO 2 ). Both CO 2 -induced groups increased, to a similar extent, brain levels of unesterified oleic, arachidonic, and docosahexaenoic acid and 1- and 2-arachidonoylglycerols compared to the microwave group in both wild-type and FAAH-KO mice. Oleoylethanolamide (OEA), arachidonoylethanolamide (AEA), and docosahexaenoylethanolamide (DHEA) levels were about 8-, 7-, and 2.5-fold higher, respectively, in the FAAH-KO mice compared with the wild-type mice. Interestingly, the concentrations of OEA, AEA, and DHEA increased 2.5- to 4-fold in response to both CO 2 -induced groups in wild-type mice, but DHEA increased only in the CO 2 group in FAAH-KO mice. Our study demonstrates that FAAH is necessary for CO 2 - induced increases in OEA and AEA but not DHEA. Targeting brain FAAH could impair the production of NAEs in response to brain injuries. © 2017 International Society for Neurochemistry.

Repetitive long-term hyperbaric oxygen treatment (HBOT administered after experimental traumatic brain injury in rats induces significant remyelination and a recovery of sensorimotor function.

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Klaus Kraitsy

Full Text Available Cells in the central nervous system rely almost exclusively on aerobic metabolism. Oxygen deprivation, such as injury-associated ischemia, results in detrimental apoptotic and necrotic cell loss. There is evidence that repetitive hyperbaric oxygen therapy (HBOT improves outcomes in traumatic brain-injured patients. However, there are no experimental studies investigating the mechanism of repetitive long-term HBOT treatment-associated protective effects. We have therefore analysed the effect of long-term repetitive HBOT treatment on brain trauma-associated cerebral modulations using the lateral fluid percussion model for rats. Trauma-associated neurological impairment regressed significantly in the group of HBO-treated animals within three weeks post trauma. Evaluation of somatosensory-evoked potentials indicated a possible remyelination of neurons in the injured hemisphere following HBOT. This presumption was confirmed by a pronounced increase in myelin basic protein isoforms, PLP expression as well as an increase in myelin following three weeks of repetitive HBO treatment. Our results indicate that protective long-term HBOT effects following brain injury is mediated by a pronounced remyelination in the ipsilateral injured cortex as substantiated by the associated recovery of sensorimotor function.

Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice.

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Ma, Elise L; Smith, Allen D; Desai, Neemesh; Cheung, Lumei; Hanscom, Marie; Stoica, Bogdan A; Loane, David J; Shea-Donohue, Terez; Faden, Alan I

2017-11-01

Traumatic brain injury (TBI) has complex effects on the gastrointestinal tract that are associated with TBI-related morbidity and mortality. We examined changes in mucosal barrier properties and enteric glial cell response in the gut after experimental TBI in mice, as well as effects of the enteric pathogen Citrobacter rodentium (Cr) on both gut and brain after injury. Moderate-level TBI was induced in C57BL/6mice by controlled cortical impact (CCI). Mucosal barrier function was assessed by transepithelial resistance, fluorescent-labelled dextran flux, and quantification of tight junction proteins. Enteric glial cell number and activation were measured by Sox10 expression and GFAP reactivity, respectively. Separate groups of mice were challenged with Cr infection during the chronic phase of TBI, and host immune response, barrier integrity, enteric glial cell reactivity, and progression of brain injury and inflammation were assessed. Chronic CCI induced changes in colon morphology, including increased mucosal depth and smooth muscle thickening. At day 28 post-CCI, increased paracellular permeability and decreased claudin-1 mRNA and protein expression were observed in the absence of inflammation in the colon. Colonic glial cell GFAP and Sox10 expression were significantly increased 28days after brain injury. Clearance of Cr and upregulation of Th1/Th17 cytokines in the colon were unaffected by CCI; however, colonic paracellular flux and enteric glial cell GFAP expression were significantly increased. Importantly, Cr infection in chronically-injured mice worsened the brain lesion injury and increased astrocyte- and microglial-mediated inflammation. These experimental studies demonstrate chronic and bidirectional brain-gut interactions after TBI, which may negatively impact late outcomes after brain injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute caffeine administration.

Science.gov (United States)

Cho, Jin Hee; Cho, Yun Ha; Kim, Hyo Young; Cha, Seung Ha; Ryu, Hyun; Jang, Wooyoung; Shin, Kyung Ho

2015-04-01

Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tai Chi Chuan and Baduanjin Increase Grey Matter Volume in Older Adults: A Brain Imaging Study.

Science.gov (United States)

Tao, Jing; Liu, Jiao; Liu, Weilin; Huang, Jia; Xue, Xiehua; Chen, Xiangli; Wu, Jinsong; Zheng, Guohua; Chen, Bai; Li, Ming; Sun, Sharon; Jorgenson, Kristen; Lang, Courtney; Hu, Kun; Chen, Shanjia; Chen, Lidian; Kong, Jian

2017-01-01

The aim of this study is to investigate and compare how 12-weeks of Tai Chi Chuan and Baduanjin exercise can modulate brain structure and memory function in older adults. Magnetic resonance imaging and memory function measurements (Wechsler Memory Scale-Chinese revised, WMS-CR) were applied at both the beginning and end of the study. Results showed that both Tai Chi Chuan and Baduanjin could significantly increase grey matter volume (GMV) in the insula, medial temporal lobe, and putamen after 12-weeks of exercise. No significant differences were observed in GMV between the Tai Chi Chuan and Baduanjin groups. We also found that compared to healthy controls, Tai Chi Chuan and Baduanjin significantly improved visual reproduction subscores on the WMS-CR. Baduanjin also improved mental control, recognition, touch, and comprehension memory subscores of the WMS-CR compared to the control group. Memory quotient and visual reproduction subscores were both associated with GMV increases in the putamen and hippocampus. Our results demonstrate the potential of Tai Chi Chuan and Baduanjin exercise for the prevention of memory deficits in older adults.

Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors.

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Wang, Lei; de Kloet, Annette D; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A; Pioquinto, David J; Ludin, Jacob A; Oh, S Paul; Katovich, Michael J; Frazier, Charles J; Raizada, Mohan K; Krause, Eric G

2016-06-01

Over-activation of the brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme 2 (ACE2) inhibits RAS activity by converting angiotensin-II, the effector peptide of RAS, to angiotensin-(1-7), which activates the Mas receptor (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ∼62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the

MicroCT and microMRI imaging of a prenatal mouse model of increased brain size

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López, Elisabeth K. N.; Stock, Stuart R.; Taketo, Makoto M.; Chenn, Anjen; Ravosa, Matthew J.

2008-08-01

There are surprisingly few experimental models of neural growth and cranial integration. This and the dearth of information regarding fetal brain development detract from a mechanistic understanding of cranial integration and its relevance to the patterning of skull form, specifically the role of encephalization on basicranial flexion. To address this shortcoming, our research uses transgenic mice expressing a stabilized form of β-catenin to isolate the effects of relative brain size on craniofacial development. These mice develop highly enlarged brains due to an increase in neural precursors, and differences between transgenic and wild-type mice are predicted to result solely from variation in brain size. Comparisons of wild-type and transgenic mice at several prenatal ages were performed using microCT (Scanco Medical MicroCT 40) and microMRI (Avance 600 WB MR spectrometer). Statistical analyses show that the larger brain of the transgenic mice is associated with a larger neurocranium and an altered basicranial morphology. However, body size and postcranial ossification do not seem to be affected by the transgene. Comparisons of the rate of postcranial and cranial ossification using microCT also point to an unexpected effect of neural growth on skull development: increased fetal encephalization may result in a compensatory decrease in the level of cranial ossification. Therefore, if other life history factors are held constant, the ontogeny of a metabolically costly structure such as a brain may occur at the expense of other cranial structures. These analyses indicate the benefits of a multifactorial approach to cranial integration using a mouse model.

Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

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Glen Daniel

2009-05-01

-lysine-bradykinin and labradimil increased the blood half-life of Gd-DTPA sufficiently enough to increase significantly the tumor tissue Gd-DTPA area under the time-concentration curve. Conclusion Metabolically stable bradykinin B2 receptor agonists, methionine-lysine-bradykinin and labradimil, enhance the transvascular delivery of small chemotherapy drugs across the BBTB of malignant gliomas by increasing the blood half-life of the co-infused drug. The selectivity of the increase in drug delivery into the malignant glioma tissue, but not into normal brain tissue or skeletal muscle tissue, is due to the inherent porous nature of the BBTB of malignant glioma microvasculature.

Anticipation and consumption of food each increase the concentration of neuroactive steroids in rat brain and plasma.

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Pisu, Maria Giuseppina; Floris, Ivan; Maciocco, Elisabetta; Serra, Mariangela; Biggio, Giovanni

2006-09-01

Stressful stimuli and anxiogenic drugs increase the plasma and brain concentrations of neuroactive steroids. Moreover, in rats trained to consume their daily meal during a fixed period, the anticipation of food is associated with changes in the function of various neurotransmitter systems. We have now evaluated the effects of anticipation and consumption of food in such trained rats on the plasma and brain concentrations of 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH PROG) and 3alpha,21-dihydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH DOC), two potent endogenous positive modulators of type A receptors for gamma-aminobutyric acid (GABA). The abundance of these neuroactive steroids was increased in both the cerebral cortex and plasma of the rats during both food anticipation and consumption. In contrast, the concentration of their precursor, progesterone, was increased in the brain only during food consumption, whereas it was increased in plasma only during food anticipation. Intraperitoneal administration of the selective agonist abecarnil (0.1 mg/kg) 40 min before food presentation prevented the increase in the brain levels of 3alpha,5alpha-TH PROG and 3alpha,5alpha-TH DOC during food anticipation but not that associated with consumption. The change in emotional state associated with food anticipation may thus result in an increase in the plasma and brain levels of 3alpha,5alpha-TH PROG and 3alpha,5alpha-TH DOC in a manner sensitive to the activation of GABA(A) receptor-mediated neurotransmission. A different mechanism, insensitive to activation of such transmission, may underlie the changes in the concentrations of these neuroactive steroids during food consumption.

Functional significance of brain glycogen in sustaining glutamatergic neurotransmission

DEFF Research Database (Denmark)

Sickmann, Helle M; Walls, Anne B; Schousboe, Arne

2009-01-01

The involvement of brain glycogen in sustaining neuronal activity has previously been demonstrated. However, to what extent energy derived from glycogen is consumed by astrocytes themselves or is transferred to the neurons in the form of lactate for oxidative metabolism to proceed is at present u...

Increased levels of deleted in malignant brain tumours 1 (DMBT1) in active bacteria-related appendicitis

DEFF Research Database (Denmark)

Kaemmerer, Elke; Schneider, Ursula; Klaus, Christina

2012-01-01

Kaemmerer E, Schneider U, Klaus C, Plum P, Reinartz A, Adolf M, Renner M, Wolfs T G A M, Kramer B W, Wagner N, Mollenhauer J & Gassler N (2012) Histopathology Increased levels of deleted in malignant brain tumours 1 (DMBT1) in active bacteria-related appendicitis Aims:  Deleted in malignant brain...

Antiretroviral treatment is associated with increased attentional load-dependent brain activation in HIV patients.

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Chang, L; Yakupov, R; Nakama, H; Stokes, B; Ernst, T

2008-06-01

The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection. Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n = 18), HIV subjects treated with antiretroviral medications (HIV+ARV, n = 12), or not treated with antiretroviral medications (HIV+NARV, n = 12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging. HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to SN (p-corrected = 0.006). HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected = 0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs. These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention.

Herpes simplex encephalitis: increased retention of Tc-99m HMPAO on acetazolamide enhanced brain perfusion SPECT

International Nuclear Information System (INIS)

Choi, Yun Young; Kim, Kwon Hyung; Kim, Seung Hyun; Cho, Suk Shin

1998-01-01

We present an interesting case of herpes simplex encephalitis, which showed increased upta unilateral temporal cortex on brain perfusion SPECT using Tc-99m HMPAO, but in bilateral tem cortex after acetazolamide administration. A 42-year-old man was admitted via emergency room, due to rapidly progressing hea disorientation and mental changes. On neurologic examination, neck stiffness and Kernig sign noted. CSF examination showed pleocytosis with lymphcyte predominance. MRI showed swelling bilateral temporal lobe with left predominance, suggestive of herpes simplex encephalitis. Baseline/ Acetazolamide brain perfusion SPECT were acquired consecutively at the same position IV administration of 740MBq and additional 1480 MBq of Tc-99m HMPAO respectively. The temporal and inferior frontal cortex showed markedly increased perfusion on the baseline acetazolamide-enhanced SPECT images. The right temporal cortex showed normal uptake on the b SPECT images, and markedly increased uptake after acetazolamide administration, which seemed to the abundant vascularity at the acute inflammation site without marked brain damage. The fo brain perfusion SPECT after 6 months showed perfusion defect in left temporal cortex but norm perfusion in right temporal cortex. Therefore, we can conclude that baseline SPECT is helpful for the prediction of the prognosis acetazolamide SPECT for the evaluation of the extent of herpes simples encephalitis

Brain Gym To Increase Academic Performance Of Children Aged 10-12 Years Old ( Experimental Study in Tembalang Elementary School and Pedalangan Elementary School Semarang)

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Marpaung, M. G.; Sareharto, T. P.; Purwanti, A.; Hermawati, D.

2017-02-01

Academic performance becomes an important determinant of individual quality. it is determined by the function of affective, cognitive, psychomotor, and intelligence. Brain gym can improve learning processes and integrate all areas that related to the learning process. To prove the effect of brain gym towards academic performance of children aged 10-12 years. This study was a quasy experiment study with one group pre and post test design. Samples (n=18 male=7 and female=11) were taken from five and six grader and conducted in Tembalang and Pedalangan Elementary School, Semarang. Pretest were administered, followed by brain gym, and post test administered in the end of study. The measurement of Intelligence Quotient pre and post test using Culture Fair Intelligence Test Scale 2. Among the 18 subjects (male=7 and female=11) the average of academic performance and IQ score after brain gym showed improvement. The Improvement of IQ score with Culture Fair Test Scale 2 was analyzed by Dependent T test showed significant results (p=0,000). The improvement of Bahasa score was analyzed by Wilcoxon test showed significant results (p=0,001), an unsignificant result were shown in Mathematics p=0,079 and natural sciences p=0,306. Brain gym can increase academic performance of children aged 10-12 years old.

Acute iron overload and oxidative stress in brain

International Nuclear Information System (INIS)

Piloni, Natacha E.; Fermandez, Virginia; Videla, Luis A.; Puntarulo, Susana

2013-01-01

An in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidative stress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concentration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6 h after Fe administration. In this in vivo Fe overload model, the ascorbyl (A·)/ascorbate (AH − ) ratio, taken as oxidative stress index, was assessed. The A·/AH − ratio in brain was significantly higher in Fe-dextran group, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactive substances (TBARS) generation rate and lipid radical (LR·) content detected by Electron Paramagnetic Resonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values of nuclear factor-kappaB deoxyribonucleic acid (NFκB DNA) binding activity were significantly increased (30%) after 8 h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21 h after Fe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold) and striatum (2.9 fold), were found at 6 h after Fe administration. CAT activity was significantly increased after 8 h of Fe administration in cortex, hippocampus and striatum (1.4 fold, 86, and 47%, respectively). Fe response in the whole brain seems to lead to enhanced NF-κB DNA binding activity, which may contribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CAT activity. Moreover, data shown here clearly indicate that even though Fe increased in several isolated brain areas, this parameter was more drastically enhanced in striatum than in cortex and hippocampus. However, comparison among the net increase in LR· generation rate, in different brain areas, showed enhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR· generation rate after 6

Analysis of a human brain transcriptome map

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Greene Jonathan R

2002-04-01

Full Text Available Abstract Background Genome wide transcriptome maps can provide tools to identify candidate genes that are over-expressed or silenced in certain disease tissue and increase our understanding of the structure and organization of the genome. Expressed Sequence Tags (ESTs from the public dbEST and proprietary Incyte LifeSeq databases were used to derive a transcript map in conjunction with the working draft assembly of the human genome sequence. Results Examination of ESTs derived from brain tissues (excluding brain tumor tissues suggests that these genes are distributed on chromosomes in a non-random fashion. Some regions on the genome are dense with brain-enriched genes while some regions lack brain-enriched genes, suggesting a significant correlation between distribution of genes along the chromosome and tissue type. ESTs from brain tumor tissues have also been mapped to the human genome working draft. We reveal that some regions enriched in brain genes show a significant decrease in gene expression in brain tumors, and, conversely that some regions lacking in brain genes show an increased level of gene expression in brain tumors. Conclusions This report demonstrates a novel approach for tissue specific transcriptome mapping using EST-based quantitative assessment.

Increasing N-acetylaspartate in the Brain during Postnatal Myelination Does Not Cause the CNS Pathologies of Canavan Disease

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Abhilash P. Appu

2017-06-01

Full Text Available Canavan disease is caused by mutations in the gene encoding aspartoacylase (ASPA, a deacetylase that catabolizes N-acetylaspartate (NAA. The precise involvement of elevated NAA in the pathogenesis of Canavan disease is an ongoing debate. In the present study, we tested the effects of elevated NAA in the brain during postnatal development. Mice were administered high doses of the hydrophobic methyl ester of NAA (M-NAA twice daily starting on day 7 after birth. This treatment increased NAA levels in the brain to those observed in the brains of Nur7 mice, an established model of Canavan disease. We evaluated various serological parameters, oxidative stress, inflammatory and neurodegeneration markers and the results showed that there were no pathological alterations in any measure with increased brain NAA levels. We examined oxidative stress markers, malondialdehyde content (indicator of lipid peroxidation, expression of NADPH oxidase and nuclear translocation of the stress-responsive transcription factor nuclear factor (erythroid-derived 2-like 2 (NRF-2 in brain. We also examined additional pathological markers by immunohistochemistry and the expression of activated caspase-3 and interleukin-6 by Western blot. None of the markers were increased in the brains of M-NAA treated mice, and no vacuoles were observed in any brain region. These results show that ASPA expression prevents the pathologies associated with excessive NAA concentrations in the brain during postnatal myelination. We hypothesize that the pathogenesis of Canavan disease involves not only disrupted NAA metabolism, but also excessive NAA related signaling processes in oligodendrocytes that have not been fully determined and we discuss some of the potential mechanisms.

A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes

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Andreas Stomby

2017-12-01

Full Text Available Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized to a Paleolithic diet (PD, n = 12 with and without high intensity exercise (PDEX, n = 12 for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group was included as a reference (n = 6. The PD included a high intake of unsaturated fatty acids and protein, and excluded the intake of dairy products, grains, refined sugar and salt. The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week. Both interventions induced a significant weight loss, improved insulin sensitivity and increased peak oxygen uptake without any significant group differences. Furthermore, both interventions were associated with increased functional brain responses within the right anterior hippocampus, right inferior occipital gyrus and increased volume of the right posterior hippocampus. There were no changes in memory performance. We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes. Putative long-term effects on cognitive functions including decreased risk of dementing disorders await further studies. Clinical trials registration number: Clinicaltrials. gov NCT01513798.

An ultra­high field Magnetic Resonance Spectroscopy study of post exercise brain lactate, glutamate and glutamine change in the human brain.

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Andrea eDennis

2015-12-01

Full Text Available During strenuous exercise there is a progressive increase in lactate uptake and metabolism into the brain as workload and plasma lactate levels increase. Although it is now widely accepted that the brain can metabolise lactate, few studies have directly measured brain lactate following vigorous exercise. Here, we used ultra-high field Magnetic Resonance Spectroscopy of the brain to obtain static measures of brain lactate, as well as brain glutamate and glutamine after vigorous exercise. The aims of our experiment were to (a track the changes in brain lactate following recovery from exercise and, (b to simultaneously measure the signals from brain glutamate and glutamine. The results of our experiment showed that vigorous exercise resulted in a significant increase in brain lactate. Furthermore, both glutamate and glutamine were successfully resolved, and as expected, although contrary to some previous reports, we did not observe any significant change in either amino acid after exercise. We did however observe a negative correlation between glutamate and a measure of fitness. These results support the hypothesis that peripherally-derived lactate is taken up by the brain when available. Our data additionally highlight the potential of ultra-high field magnetic resonance spectroscopy as a non-invasive way of measuring multiple brain metabolite changes with exercise.

Global cerebral blood flow changes measured by brain perfusion SPECT immediately after whole brain irradiation

International Nuclear Information System (INIS)

Ohtawa, Nobuyuki; Machida, Kikuo; Honda, Norinari; Hosono, Makoto; Takahashi, Takeo

2003-01-01

Whole brain irradiation (WBI) is still a major treatment option for patients with metastatic brain tumor despite recent advances in chemotherapy and newer techniques of radiation therapy. Cerebral blood flow (CBF) of changes induced by whole brain radiation is not fully investigated, and the aim of the study was to measure CBF changes non-invasively with brain perfusion SPECT to correlate with treatment effect or prognosis. Total of 106 patients underwent WBI during April 1998 to March 2002. Both brain MRI and brain perfusion SPECT could be performed before (less than 1 week before or less than 10 Gy of WBI) and immediately after (between 1 week before and 2 weeks after the completion of WBI) the therapy in 17 of these patients. They, 10 men and 7 women, all had metastatic brain tumor with age range of 45 to 87 (mean of 61.4) years. Tc-99m brain perfusion agent (HMPAO in 4, ECD in 13) was rapidly administered in a 740-MBq dose to measure global and regional CBF according to Matsuda's method, which based on both Patlak plot and Lassens' linearity correction. Brain MRI was used to measure therapeutic response according to World Health Organization (WHO) classification as complete remission (CR), partial response (PR), no change (NC), and progressive disease (PD). Survival period was measured from the completion of WBI. Mean global CBF was 40.6 and 41.5 ml/100 g/min before and immediately after the WBI, respectively. Four patients increased (greater than 10%) their global mean CBF, 10 unchanged (less than 10% increase or decrease), and 3 decreased after the WBI. The WBI achieved CR in none, PR in 8, NC in 6, and PD in 3 on brain MRI. Change in global mean CBF (mean±SD) was significantly larger in PR (4.3±2.0 ml/100 g/min, p=0.002) and in NC (-0.1±4.5) than in PD (-3.9±6.4, P=0.002, P=0.016, respectively). Survival was not significantly (p>0.05) different among the patients with CR (20 weeks), NC (48 weeks), and PD (21 weeks). Change in global CBF and survival was

Transcranial low-level laser therapy increases memory, learning, neuroprogenitor cells, BDNF and synaptogenesis in mice with traumatic brain injury

Science.gov (United States)

Xuan, Weijun; Huang, Liyi; Vatansever, Fatma; Agrawal, Tanupriya; Hamblin, Michael R.

2015-03-01

Increasing concern is evident over the epidemic of traumatic brain injury in both civilian and military medicine, and the lack of approved treatments. Transcranial low level laser therapy tLLLT) is a new approach in which near infrared laser is delivered to the head, penetrates the scalp and skull to reach the brain. We asked whether tLLLT at 810-nm could improve memory and learning in mice with controlled cortical impact traumatic brain injury. We investigated the mechanism of action by immunofluorescence studies in sections from brains of mice sacrificed at different times. Mice with TBI treated with 1 or 3 daily laser applications performed better on Morris Water Maze test at 28 days. Laser treated mice had increased BrdU incorporation into NeuN positive cells in the dentate gyrus and subventricular zone indicating formation of neuroprogenitor cells at 7 days and less at 28 days. Markers of neuron migration (DCX and Tuj1) were also increased, as was the neurotrophin, brain derived neurotrophic factor (BDNF) at 7 days. Markers of synaptogenesis (formation of new connections between existing neurons) were increased in the perilesional cortex at 28 days. tLLLT is proposed to be able to induce the brain to repair itself after injury. However its ability to induce neurogenesis and synaptogenesis suggests that tLLLT may have much wider applications to neurodegenerative and psychiatric disorders.

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

Science.gov (United States)

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

2011-01-01

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

Increased orbitofrontal brain activation after administration of a selective adenosine A2A antagonist in cocaine dependent subjects

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F. Gerard eMoeller

2012-05-01

Full Text Available Background: Positron Emission Tomography imaging studies provide evidence of reduced dopamine function in cocaine dependent subjects in the striatum, which is correlated with prefrontal cortical glucose metabolism, particularly in the orbitofrontal cortex. However, whether enhancement of dopamine in the striatum in cocaine dependent subjects would be associated with changes in prefrontal cortical brain activation is unknown. One novel class of medications that enhance dopamine function via heteromer formation with dopamine receptors in the striatum is the selective adenosine A2A receptor antagonists. This study sought to determine the effects administration of the selective adenosine A2A receptor antagonist SYN115 on brain function in cocaine dependent subjects. Methodology/Principle Findings: Twelve cocaine dependent subjects underwent two fMRI scans (one after a dose of placebo and one after a dose of 100 mg of SYN115 while performing a working memory task with 3 levels of difficulty (3, 5, and 7 digits. fMRI results showed that for 7-digit working memory activation there was significantly greater activation from SYN115 compared to placebo in portions of left (L lateral orbitofrontal cortex, L insula, and L superior and middle temporal pole. Conclusion/Significance: These findings are consistent with enhanced dopamine function in the striatum in cocaine dependent subjects via blockade of adenosine A2A receptors producing increased brain activation in the orbitofrontal cortex and other cortical regions. This suggests that at least some of the changes in brain activation in prefrontal cortical regions in cocaine dependent subjects may be related to altered striatal dopamine function, and that enhancement of dopamine function via adenosine A2A receptor blockade could be explored further for amelioration of neurobehavioral deficits associated with chronic cocaine use.

Functional significance of brain glycogen in sustaining glutamatergic neurotransmission.

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Sickmann, Helle M; Walls, Anne B; Schousboe, Arne; Bouman, Stephan D; Waagepetersen, Helle S

2009-05-01

The involvement of brain glycogen in sustaining neuronal activity has previously been demonstrated. However, to what extent energy derived from glycogen is consumed by astrocytes themselves or is transferred to the neurons in the form of lactate for oxidative metabolism to proceed is at present unclear. The significance of glycogen in fueling glutamate uptake into astrocytes was specifically addressed in cultured astrocytes. Moreover, the objective was to elucidate whether glycogen derived energy is important for maintaining glutamatergic neurotransmission, induced by repetitive exposure to NMDA in co-cultures of cerebellar neurons and astrocytes. In the astrocytes it was shown that uptake of the glutamate analogue D-[3H]aspartate was impaired when glycogen degradation was inhibited irrespective of the presence of glucose, signifying that energy derived from glycogen degradation is important for the astrocytic compartment. By inhibiting glycogen degradation in co-cultures it was evident that glycogen provides energy to sustain glutamatergic neurotransmission, i.e. release and uptake of glutamate. The relocation of glycogen derived lactate to the neuronal compartment was investigated by employing d-lactate, a competitive substrate for the monocarboxylate transporters. Neurotransmitter release was affected by the presence of d-lactate indicating that glycogen derived energy is important not only in the astrocytic but also in the neuronal compartment.

Increase in the penetration of tracer compounds into the rat brain during 2-methyl-4-chlorophenoxyacetic acid (MCPA) intoxication

International Nuclear Information System (INIS)

Elo, H.A.; Ylitalo, P.; Kyoettilae, J.; Hervonen, H.

1982-01-01

The penetration of different intravenous tracer molecules such as 14 C-labelled 2-methyl-4-chlorophenoxyacetic acid ( 14 C-MCPA), 14 C-p-aminobenzoic acid ( 14 C-PABA), 14 C-sucrose, 14 C-antipyrine and iodinated ( 125 I) human albumin ( 125 I-HA) into the brain and cerebrospinal fluid (CSF) was studied in MCPA-intoxicated and control rats. Toxic subcutaneous doses of sodium salt of MCPA (200-500 mg/kg) increased highly the brain/plasma and CSF/plasma ratios of 14 C-MCPA and 14 C-PABA, as compared to the muscle/plasma ratio. Probenecid (200 mg/kg) did not affect the cerebral MCPA concentration in the intoxicated animals. The tissue/plasma ratios of 14 C-sucrose, 14 C-antipyrine and 125 I-HA were also increased in the brain and CSF of intoxicated animals, but the increases were less pronounced than those of 14 C-MCPA or 14 C-PABA. The results indicate that MCPA intoxication caused a selective damage of the blood-brain barrier in the brain areas studied. (author)

Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain.

Science.gov (United States)

Sawicki, C M; McKim, D B; Wohleb, E S; Jarrett, B L; Reader, B F; Norden, D M; Godbout, J P; Sheridan, J F

2015-08-27

Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b(+) cells (microglia/macrophages) and enriched GLAST-1(+)/CD11b(-) cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain region-dependent manner. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights

Inside the Diabetic Brain

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Chomova M.

2014-12-01

Full Text Available CNS complications resulting from diabetes mellitus (DM are a problem gaining more acceptance and attention in the recent years. Both types 1 and 2 DM represent an significant risk factor for decreased cognitive functions, memory and learning deficits as well as development of Alzheimer’s disease. Chronic hyperglycemia through protein glycation and increased oxidative stress contributes to brain dysfunction, however increasing evidences suggest that the pathology of DM in the brain involves a progressive and coordinated disruption of insulin signaling, with profound consequences for brain function and plasticity. Since many of the CNS changes observed in diabetic patients and animal models of DM are reminiscent of the changes seen in aging, the theory of advanced brain aging in DM has been proposed. This review summarizes the findings of the literature regarding the effects of DM on the brain in the terms of diabetes-related metabolic derangements and intracellular signaling.

Increased glucocerebrosidase (GBA) 2 activity in GBA1 deficient mice brains and in Gaucher leucocytes.

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Burke, Derek G; Rahim, Ahad A; Waddington, Simon N; Karlsson, Stefan; Enquist, Ida; Bhatia, Kailash; Mehta, Atul; Vellodi, Ashok; Heales, Simon

2013-09-01

Lysosomal glucocerebrosidase (GBA1) deficiency is causative for Gaucher disease. Not all individuals with GBA1 mutations develop neurological involvement raising the possibility that other factors may provide compensatory protection. One factor may be the activity of the non-lysosomal β-glucosidase (GBA2) which exhibits catalytic activity towards glucosylceramide and is reported to be highly expressed in brain tissue. Here, we assessed brain GBA2 enzymatic activity in wild type, heterozygote and GBA1 deficient mice. Additionally, we determined activity in leucocytes obtained from 13 patients with Gaucher disease, 10 patients with enzymology consistent with heterozygote status and 19 controls. For wild type animals, GBA2 accounted for over 85 % of total brain GBA activity and was significantly elevated in GBA1 deficient mice when compared to heterozygote and wild types (GBA1 deficient; 92.4 ± 5.6, heterozygote; 71.5 ± 2.4, wild type 76.8 ± 5.1 nmol/h/mg protein). For the patient samples, five Gaucher patients had GBA2 leucocyte activities markedly greater than controls. No difference in GBA2 activity was apparent between the control and carrier groups. Undetectable GBA2 activity was identified in four leucocyte preparations; one in the control group, two in the carrier group and one from the Gaucher disease group. Work is now required to ascertain whether GBA2 activity is a disease modifying factor in Gaucher disease and to identify the mechanism(s) responsible for triggering increased GBA2 activity in GBA1 deficiency states.

Increased seroreactivity to glioma-expressed antigen 2 in brain tumor patients under radiation.

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Sabrina M Heisel

Full Text Available BACKGROUND: Surgery and radiation are the mainstays of therapy for human gliomas that are the most common primary brain tumors. Most recently, cell culture and animal studies provided the first convincing evidence that radiation not only eliminates tumor cells, but also modulates the immune response and likely improves anti-tumor immunotherapy. METHODOLOGY/PRINCIPAL FINDINGS: We present an in vivo study that analyzes the effects of radiation on the immune response in tumor patients. As readout system, we utilized the reactivity of glioma patients' sera against antigen GLEA2 as the most frequent antigen immunogenic in glioblastoma patients. We established an ELISA assay to analyze reactivity of 24 glioblastoma patients over a period of several months. As control we used 30 sera from healthy donors as well as 30 sera from lung cancer patients. We compared the course of GLEA2 seroreactivity at different times prior, during and after radiation. The GLEA2 seroreactivity was increased by the time of surgery, decreased after surgery, increased again under radiation, and slightly decreased after radiation. CONCLUSIONS/SIGNIFICANCE: Our results provide in vivo evidence for an increased antibody response against tumor antigens under radiation. Antigens that become immunogenic with an increased antibody response as result of radiation can serve as ideal targets for immunotherapy of human tumors.

Reproducibility of Dynamic Computed Tomography Brain Perfusion Measurements in Patients with Significant Carotid Artery Stenosis

International Nuclear Information System (INIS)

Serafin, Z.; Kotarski, M.; Karolkiewicz, M.; Mindykowski, R.; Lasek, W.; Molski, S.; Gajdzinska, M.; Nowak-Nowacka, A.

2009-01-01

Background: Perfusion computed tomography (PCT) determination is a minimally invasive and widely available technique for brain blood flow assessment, but its application may be restricted by large variation of results. Purpose: To determine the intraobserver, interobserver, and inter examination variability of brain PCT absolute measurements in patients with significant carotid artery stenosis (CAS), and to evaluate the effect of the use of relative perfusion values on PCT reproducibility. Material and Methods: PCT imaging was completed in 61 patients before endarterectomy, and in 38 of these within 4 weeks after treatment. Cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), and peak enhancement intensity (PEI) were calculated with the maximum slope method. Inter examination variability was evaluated based on perfusion of hemisphere contralateral to the treated CAS, from repeated examinations. Interobserver and intraobserver variability were established for the untreated side, based on pretreatment examination. Results: Interobserver and intraobserver variability were highest for CBF measurement (28.8% and 32.5%, respectively), and inter examination variability was the highest for CBV (24.1%). Intraobserver and interobserver variability were higher for absolute perfusion values compared with their respective ratios for CBF and TTP. The only statistically significant difference between perfusion values measured by two observers was for CBF (mean 78.3 vs. 67.5 ml/100 g/min). The inter examination variability of TTP (12.1%) was significantly lower than the variability of other absolute perfusion measures, and the inter examination variability of ratios was significantly lower than absolute values for all the parameters. Conclusion: In longitudinal studies of patients with chronic cerebral ischemia, PCT ratios and either TTP or CBV are more suitable measures than absolute CBF values, because of their considerably lower inter- and intraobserver

Reproducibility of Dynamic Computed Tomography Brain Perfusion Measurements in Patients with Significant Carotid Artery Stenosis

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Serafin, Z.; Kotarski, M.; Karolkiewicz, M.; Mindykowski, R.; Lasek, W.; Molski, S.; Gajdzinska, M.; Nowak-Nowacka, A. (Dept. of Radiology and Diagnostic Imaging, and Dept. of General and Vascular Surgery, Nicolaus Copernicus Univ., Collegium Medicum, Bydgoszcz (Poland))

2009-02-15

Background: Perfusion computed tomography (PCT) determination is a minimally invasive and widely available technique for brain blood flow assessment, but its application may be restricted by large variation of results. Purpose: To determine the intraobserver, interobserver, and inter examination variability of brain PCT absolute measurements in patients with significant carotid artery stenosis (CAS), and to evaluate the effect of the use of relative perfusion values on PCT reproducibility. Material and Methods: PCT imaging was completed in 61 patients before endarterectomy, and in 38 of these within 4 weeks after treatment. Cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), and peak enhancement intensity (PEI) were calculated with the maximum slope method. Inter examination variability was evaluated based on perfusion of hemisphere contralateral to the treated CAS, from repeated examinations. Interobserver and intraobserver variability were established for the untreated side, based on pretreatment examination. Results: Interobserver and intraobserver variability were highest for CBF measurement (28.8% and 32.5%, respectively), and inter examination variability was the highest for CBV (24.1%). Intraobserver and interobserver variability were higher for absolute perfusion values compared with their respective ratios for CBF and TTP. The only statistically significant difference between perfusion values measured by two observers was for CBF (mean 78.3 vs. 67.5 ml/100 g/min). The inter examination variability of TTP (12.1%) was significantly lower than the variability of other absolute perfusion measures, and the inter examination variability of ratios was significantly lower than absolute values for all the parameters. Conclusion: In longitudinal studies of patients with chronic cerebral ischemia, PCT ratios and either TTP or CBV are more suitable measures than absolute CBF values, because of their considerably lower inter- and intraobserver

Changes in brain CT with aging

International Nuclear Information System (INIS)

Hiraiwa, Mikio; Abe, Toshiaki; Nonaka, Chizuru

1983-01-01

We have devised a new method for the objective evaluation of brain CT, a two-dimensional measurement: Two-dimensional measurement is based not on the developed films, but on treating raw data from magnetic tape. On the basis of our application of this method, we have discussed the changes in brain CT with aging. 135 patients, 72 males and 63 females, aged from 10 days to 78 years old, were subjected. The intracranial area showed a significant increase under 2 years old, but no marked changes after 3 years of age. The brain area increased under 2 years of age, and decreased after one's forties. The ventricular area showed no significant changes until the forties, but gradually increased thereafter. The bifrontal fluid-collection area was prominent in infancy, was almost invisible between 3 and 50 years of age and thereafter grew larger. For a relative comparison of brain CT scans with different intracranial areas, we devised three indices; BAI (brain-area index; brain area x 100/intracranial area), VAI (ventricular-area index; ventricular area x 100/intracranial area), and BFCI (bifrontal fluid-collection-area index; bifrontal fluid-collection area x 100/intracranial area). The BAI was low in infancy (under 95), was 96-97 between 3 and 50 years of age, and slowly decreased thereafter (88 in seventies). The VAI was under 2 until 50 years of age and gradually increased thereafter. The BFCI was high (over 3) in infancy and 0.2-0.4 between 3 and 50 years of age, and slowly increased thereafter. (J.P.N.)

Impaired rich club and increased local connectivity in children with traumatic brain injury: Local support for the rich?

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Verhelst, Helena; Vander Linden, Catharine; De Pauw, Toon; Vingerhoets, Guy; Caeyenberghs, Karen

2018-03-12

Recent evidence has shown the presence of a "rich club" in the brain, which constitutes a core network of highly interconnected and spatially distributed brain regions, important for high-order cognitive processes. This study aimed to map the rich club organization in 17 young patients with moderate to severe TBI (15.71 ± 1.75 years) in the chronic stage of recovery and 17 age- and gender-matched controls. Probabilistic tractography was performed on diffusion weighted imaging data to construct the edges of the structural connectomes using number of streamlines as edge weight. In addition, the whole-brain network was divided into a rich club network, a local network and a feeder network connecting the latter two. Functional outcome was measured with a parent questionnaire for executive functioning. Our results revealed a significantly decreased rich club organization (p values < .05) and impaired executive functioning (p < .001) in young patients with TBI compared with controls. Specifically, we observed reduced density values in all three subnetworks (p values < .005) and a reduced mean strength in the rich club network (p = .013) together with an increased mean strength in the local network (p = .002) in patients with TBI. This study provides new insights into the nature of TBI-induced brain network alterations and supports the hypothesis that the local subnetwork tries to compensate for the biologically costly subnetwork of rich club nodes after TBI. © 2018 Wiley Periodicals, Inc.

Correlation between increased platelet ADP aggregability and silent brain infarcts

International Nuclear Information System (INIS)

Ono, Kenichiro; Arimoto, Hirohiko; Shirotani, Toshiki

2012-01-01

The purpose of this study was to investigate the correlation between platelet aggregability and silent brain infarcts. The study subjects were 445 people (264 men, 181 women; mean age, 53±14 years) with no neurologic signs, history of brain tumor, trauma, cerebrovascular disease, or antiplatelet medications. Adenosine diphosphate (ADP)-induced platelet aggregation was measured by the aggregation-size analytic method. Platelet aggregability was classified into 9 classes. The presence of headache/vertigo, hypertension, diabetes mellitus, hyperlipidemia, or smoking was elicited by questioning or blood sampling. A head MRI scan was performed, and if marked atherosclerosis or obvious stenosis in the intracranial vessels was detected, it was defined as a positive MR angiography (MRA) finding. Silent brain infarcts were detected in 26.3% of subjects. Hyperaggregability defined as that above class 6, 7, and 8 was present in 43.8%, 30.8%, and 15.7% of subjects, respectively. The risk factors for silent brain infarcts by multiple logistic regression analysis were aging, hypertension, positive MRA findings, and hyperaggregability. Platelet ADP hyperaggregability might be a risk factor for silent brain infarcts. (author)

P-glycoprotein Inhibition Increases the Brain Distribution and Antidepressant-Like Activity of Escitalopram in Rodents

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O'Brien, Fionn E; O'Connor, Richard M; Clarke, Gerard; Dinan, Timothy G; Griffin, Brendan T; Cryan, John F

2013-01-01

Despite the clinical prevalence of the antidepressant escitalopram, over 30% of escitalopram-treated patients fail to respond to treatment. Recent gene association studies have highlighted a potential link between the drug efflux transporter P-glycoprotein (P-gp) and response to escitalopram. The present studies investigated pharmacokinetic and pharmacodynamic interactions between P-gp and escitalopram. In vitro bidirectional transport studies revealed that escitalopram is a transported substrate of human P-gp. Microdialysis-based pharmacokinetic studies demonstrated that administration of the P-gp inhibitor cyclosporin A resulted in increased brain levels of escitalopram without altering plasma escitalopram levels in the rat, thereby showing that P-gp restricts escitalopram transport across the blood–brain barrier (BBB) in vivo. The tail suspension test (TST) was carried out to elucidate the pharmacodynamic impact of P-gp inhibition on escitalopram effect in a mouse model of antidepressant activity. Pre-treatment with the P-gp inhibitor verapamil enhanced the response to escitalopram in the TST. Taken together, these data indicate that P-gp may restrict the BBB transport of escitalopram in humans, potentially resulting in subtherapeutic brain concentrations in certain patients. Moreover, by verifying that increasing escitalopram delivery to the brain by P-gp inhibition results in enhanced antidepressant-like activity, we suggest that adjunctive treatment with a P-gp inhibitor may represent a beneficial approach to augment escitalopram therapy in depression. PMID:23670590

Increased Cortical Gamma-Aminobutyric Acid Precedes Incomplete Extinction of Conditioned Fear and Increased Hippocampal Excitatory Tone in a Mouse Model of Mild Traumatic Brain Injury.

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Schneider, Brandy L; Ghoddoussi, Farhad; Charlton, Jennifer L; Kohler, Robert J; Galloway, Matthew P; Perrine, Shane A; Conti, Alana C

2016-09-01

Mild traumatic brain injury (mTBI) contributes to development of affective disorders, including post-traumatic stress disorder (PTSD). Psychiatric symptoms typically emerge in a tardive fashion post-TBI, with negative effects on recovery. Patients with PTSD, as well as rodent models of PTSD, demonstrate structural and functional changes in brain regions mediating fear learning, including prefrontal cortex (PFC), amygdala (AMYG), and hippocampus (HC). These changes may reflect loss of top-down control by which PFC normally exhibits inhibitory influence over AMYG reactivity to fearful stimuli, with HC contribution. Considering the susceptibility of these regions to injury, we examined fear conditioning (FC) in the delayed post-injury period, using a mouse model of mTBI. Mice with mTBI displayed enhanced acquisition and delayed extinction of FC. Using proton magnetic resonance spectroscopy ex vivo, we examined PFC, AMYG, and HC levels of gamma-aminobutyric acid (GABA) and glutamate as surrogate measures of inhibitory and excitatory neurotransmission, respectively. Eight days post-injury, GABA was increased in PFC, with no significant changes in AMYG. In animals receiving FC and mTBI, glutamate trended toward an increase and the GABA/glutamate ratio decreased in ventral HC at 25 days post-injury, whereas GABA decreased and GABA/glutamate decreased in dorsal HC. These neurochemical changes are consistent with early TBI-induced PFC hypoactivation facilitating the fear learning circuit and exacerbating behavioral fear responses. The latent emergence of overall increased excitatory tone in the HC, despite distinct plasticity in dorsal and ventral HC fields, may be associated with disordered memory function, manifested as incomplete extinction and enhanced FC recall.

Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

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Anja Kafka

2014-06-01

Full Text Available The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1, Dishevelled-3 (DVL3, E-cadherin (CDH1 and beta-catenin (CTNNB1. Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR/loss of heterozygosity (LOH. Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001. Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC were significantly associated to CDH1 LOH (p = 0.001. Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

Increased transfer of 45Ca into brain and cerebrospinal fluid from plasma during chronic hypocalcemia in rats.

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Murphy, V A; Rapoport, S I

1988-06-28

Recent studies have shown regulation of central nervous system [Ca] after chronic hypo- and hypercalcemia. To investigate the mechanism of this regulation, 3-week-old rats were fed diets for 8 weeks that contained low or normal levels of Ca. Plasma [Ca] was 40% less in rats fed the low Ca diet than in animals fed normal diet. Unidirectional transfer coefficients for Ca (KCa) and Cl (KCl) into cerebrospinal fluid (CSF) and brain were determined from the 10 min uptake of intravenously injected 45Ca and 36Cl in awake animals. KCa for CSF was 68% greater in low-Ca rats than in normal rats. Likewise, the values of KCa for brain regions with areas adjacent to the ventricles like the hippocampus and pons-medulla were 50% higher than in normal animals. On the other hand, KCas for parietal cortex, a brain region distant from the choroid plexus and not expected to be influenced by Ca entry into CSF, were similar between the groups. Comparison of the regional ratios of KCa/KCl revealed that a selective increase of Ca transport occurred into CSF and all brain regions except the parietal cortex in Ca-deficient rats. The results suggest that Ca homeostasis of CSF and brain [Ca] during chronic hypocalcemia is due to increased transfer of Ca from blood to brain, and that the regulation occurs via the CSF, possibly at the choroid plexus, but not via the cerebral capillaries.

Red Brain, Blue Brain: Evaluative Processes Differ in Democrats and Republicans

Science.gov (United States)

Schreiber, Darren; Fonzo, Greg; Simmons, Alan N.; Dawes, Christopher T.; Flagan, Taru; Fowler, James H.; Paulus, Martin P.

2013-01-01

Liberals and conservatives exhibit different cognitive styles and converging lines of evidence suggest that biology influences differences in their political attitudes and beliefs. In particular, a recent study of young adults suggests that liberals and conservatives have significantly different brain structure, with liberals showing increased gray matter volume in the anterior cingulate cortex, and conservatives showing increased gray matter volume in the in the amygdala. Here, we explore differences in brain function in liberals and conservatives by matching publicly-available voter records to 82 subjects who performed a risk-taking task during functional imaging. Although the risk-taking behavior of Democrats (liberals) and Republicans (conservatives) did not differ, their brain activity did. Democrats showed significantly greater activity in the left insula, while Republicans showed significantly greater activity in the right amygdala. In fact, a two parameter model of partisanship based on amygdala and insula activations yields a better fitting model of partisanship than a well-established model based on parental socialization of party identification long thought to be one of the core findings of political science. These results suggest that liberals and conservatives engage different cognitive processes when they think about risk, and they support recent evidence that conservatives show greater sensitivity to threatening stimuli. PMID:23418419

Age and lesion-induced increases of GDNF transgene expression in brain following intracerebral injections of DNA nanoparticles.

Science.gov (United States)

Yurek, D M; Hasselrot, U; Cass, W A; Sesenoglu-Laird, O; Padegimas, L; Cooper, M J

2015-01-22

In previous studies that used compacted DNA nanoparticles (DNP) to transfect cells in the brain, we observed higher transgene expression in the denervated striatum when compared to transgene expression in the intact striatum. We also observed that long-term transgene expression occurred in astrocytes as well as neurons. Based on these findings, we hypothesized that the higher transgene expression observed in the denervated striatum may be a function of increased gliosis. Several aging studies have also reported an increase of gliosis as a function of normal aging. In this study we used DNPs that encoded for human glial cell line-derived neurotrophic factor (hGDNF) and either a non-specific human polyubiquitin C (UbC) or an astrocyte-specific human glial fibrillary acidic protein (GFAP) promoter. The DNPs were injected intracerebrally into the denervated or intact striatum of young, middle-aged or aged rats, and glial cell line-derived neurotrophic factor (GDNF) transgene expression was subsequently quantified in brain tissue samples. The results of our studies confirmed our earlier finding that transgene expression was higher in the denervated striatum when compared to intact striatum for DNPs incorporating either promoter. In addition, we observed significantly higher transgene expression in the denervated striatum of old rats when compared to young rats following injections of both types of DNPs. Stereological analysis of GFAP+ cells in the striatum confirmed an increase of GFAP+ cells in the denervated striatum when compared to the intact striatum and also an age-related increase; importantly, increases in GFAP+ cells closely matched the increases in GDNF transgene levels. Thus neurodegeneration and aging may lay a foundation that is actually beneficial for this particular type of gene therapy while other gene therapy techniques that target neurons are actually targeting cells that are decreasing as the disease progresses. Copyright © 2014 IBRO. Published by

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

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......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...

Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain.

Science.gov (United States)

Jensen, Vivi F H; Mølck, Anne-Marie; Chapman, Melissa; Alifrangis, Lene; Andersen, Lene; Lykkesfeldt, Jens; Bøgh, Ingrid B

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 neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced.

Slow induction of brain death leads to decreased renal function and increased hepatic apoptosis in rats

NARCIS (Netherlands)

Rebolledo, Rolando A.; Hoeksma, Dane; Hottenrott, Christina M. V.; Bodar, Yves J. L.; Ottens, Petra J.; Wiersema-Buist, Janneka; Leuvenink, Henri G. D.

2016-01-01

Background: Donor brain death (BD) is an independent risk factor for graft survival in recipients. While in some patients BD results from a fast increase in intracranial pressure, usually associated with trauma, in others, intracranial pressure increases more slowly. The speed of intracranial

Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury.

Science.gov (United States)

Kim, Jae Young; Lee, Yong Woo; Kim, Jae Hwan; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

2015-07-01

Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-κB (NF-κB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-κB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.

Increased Brain Activation for Foot Movement During 70-Day 6 Deg Head-Down Bed Rest (HDBR): Evidence from Functional Magnetic Resonance Imaging (fMRI)

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Yuan, P.; Koppelmans, V.; Cassady, K.; Cooke, K.; De Dios, Y. E.; Stepanyan, V.; Szecsy, D.; Gadd, N.; Wood, S. J.; Reuter-Lorenz, P. A.;

Brain functional network connectivity based on a visual task: visual information processing-related brain regions are significantly activated in the task state

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Yan-li Yang

2015-01-01

Full Text Available It is not clear whether the method used in functional brain-network related research can be applied to explore the feature binding mechanism of visual perception. In this study, we investigated feature binding of color and shape in visual perception. Functional magnetic resonance imaging data were collected from 38 healthy volunteers at rest and while performing a visual perception task to construct brain networks active during resting and task states. Results showed that brain regions involved in visual information processing were obviously activated during the task. The components were partitioned using a greedy algorithm, indicating the visual network existed during the resting state. Z-values in the vision-related brain regions were calculated, confirming the dynamic balance of the brain network. Connectivity between brain regions was determined, and the result showed that occipital and lingual gyri were stable brain regions in the visual system network, the parietal lobe played a very important role in the binding process of color features and shape features, and the fusiform and inferior temporal gyri were crucial for processing color and shape information. Experimental findings indicate that understanding visual feature binding and cognitive processes will help establish computational models of vision, improve image recognition technology, and provide a new theoretical mechanism for feature binding in visual perception.

Meditation is associated with increased brain network integration.

Science.gov (United States)

van Lutterveld, Remko; van Dellen, Edwin; Pal, Prasanta; Yang, Hua; Stam, Cornelis Jan; Brewer, Judson

2017-09-01

This study aims to identify novel quantitative EEG measures associated with mindfulness meditation. As there is some evidence that meditation is associated with higher integration of brain networks, we focused on EEG measures of network integration. Sixteen novice meditators and sixteen experienced meditators participated in the study. Novice meditators performed a basic meditation practice that supported effortless awareness, which is an important quality of experience related to mindfulness practices, while their EEG was recorded. Experienced meditators performed a self-selected meditation practice that supported effortless awareness. Network integration was analyzed with maximum betweenness centrality and leaf fraction (which both correlate positively with network integration) as well as with diameter and average eccentricity (which both correlate negatively with network integration), based on a phase-lag index (PLI) and minimum spanning tree (MST) approach. Differences between groups were assessed using repeated-measures ANOVA for the theta (4-8 Hz), alpha (8-13 Hz) and lower beta (13-20 Hz) frequency bands. Maximum betweenness centrality was significantly higher in experienced meditators than in novices (P = 0.012) in the alpha band. In the same frequency band, leaf fraction showed a trend toward being significantly higher in experienced meditators than in novices (P = 0.056), while diameter and average eccentricity were significantly lower in experienced meditators than in novices (P = 0.016 and P = 0.028 respectively). No significant differences between groups were observed for the theta and beta frequency bands. These results show that alpha band functional network topology is better integrated in experienced meditators than in novice meditators during meditation. This novel finding provides the rationale to investigate the temporal relation between measures of functional connectivity network integration and meditation quality, for example using

Increased intrinsic brain connectivity between pons and somatosensory cortex during attacks of migraine with aura

DEFF Research Database (Denmark)

Hougaard, Anders; Amin, Faisal Mohammad; Larsson, Henrik B W

2017-01-01

The neurological disturbances of migraine aura are caused by transient cortical dysfunction due to waves of spreading depolarization that disrupt neuronal signaling. The effects of these cortical events on intrinsic brain connectivity during attacks of migraine aura have not previously been......-based approach focusing on cortical visual areas and areas involved in migraine pain, and a data-driven independent component analysis approach to detect changes in intrinsic brain signaling during attacks. In addition, we performed the analyses after mirroring the MRI data according to the side of perceived......-sided pain. For aura-side normalized data, we found increased connectivity during attacks between visual area V5 and the lower middle frontal gyrus in the symptomatic hemisphere (peak voxel: P = 0.0194, (x, y, z) = (40, 40, 12). The present study provides evidence of altered intrinsic brain connectivity...

Increased determinism in brain electrical activity occurs in association with multiple sclerosis.

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Carrubba, Simona; Minagar, Alireza; Chesson, Andrew L; Frilot, Clifton; Marino, Andrew A

2012-04-01

Increased determinism (decreased complexity) of brain electrical activity has been associated with some brain diseases. Our objective was to determine whether a similar association occurred for multiple sclerosis (MS). Ten subjects with a relapsing-remitting course of MS who were in remission were studied; the controls were age- and gender-matched clinically normal subjects. Recurrence plots were calculated using representative electroencephalogram (EEG) epochs (1-7 seconds) from six derivations; the plots were quantified using the nonlinear variables percent recurrence (%R) and percent determinism (%D). The results were averaged over all derivations for each participant, and the means were compared between the groups. As a linear control procedure the groups were also compared using spectral analysis. The mean±SD of %R for the MS subjects was 6·6±1·3%, compared with 5·1±1·3% in the normal group (P = 0·017), indicating that brain activity in the subjects with MS was less complex, as hypothesized. The groups were not distinguishable using %D or spectral analysis. Taken together with our earlier report that %R could be used to discriminate between MS and normal subjects based on the ability to exhibit evoked potentials, the evidence suggests that complexity analysis of the EEG has potential for development as a diagnostic test for MS.

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

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

1985-12-01

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

Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain

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Vivi F. H. Jensen

2017-01-01

Full Text Available 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 neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced.

Parent-child intervention decreases stress and increases maternal brain activity and connectivity during own baby-cry: An exploratory study.

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Swain, James E; Ho, S Shaun; Rosenblum, Katherine L; Morelen, Diana; Dayton, Carolyn J; Muzik, Maria

2017-05-01

Parental responses to their children are crucially influenced by stress. However, brain-based mechanistic understanding of the adverse effects of parenting stress and benefits of therapeutic interventions is lacking. We studied maternal brain responses to salient child signals as a function of Mom Power (MP), an attachment-based parenting intervention established to decrease maternal distress. Twenty-nine mothers underwent two functional magnetic resonance imaging brain scans during a baby-cry task designed to solicit maternal responses to child's or self's distress signals. Between scans, mothers were pseudorandomly assigned to either MP (n = 14) or control (n = 15) with groups balanced for depression. Compared to control, MP decreased parenting stress and increased child-focused responses in social brain areas highlighted by the precuneus and its functional connectivity with subgenual anterior cingulate cortex, which are key components of reflective self-awareness and decision-making neurocircuitry. Furthermore, over 13 weeks, reduction in parenting stress was related to increasing child- versus self-focused baby-cry responses in amygdala-temporal pole functional connectivity, which may mediate maternal ability to take her child's perspective. Although replication in larger samples is needed, the results of this first parental-brain intervention study demonstrate robust stress-related brain circuits for maternal care that can be modulated by psychotherapy.

Premature infants display increased noxious-evoked neuronal activity in the brain compared to healthy age-matched term-born infants.

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Slater, Rebeccah; Fabrizi, Lorenzo; Worley, Alan; Meek, Judith; Boyd, Stewart; Fitzgerald, Maria

2010-08-15

This study demonstrates that infants who are born prematurely and who have experienced at least 40days of intensive or special care have increased brain neuronal responses to noxious stimuli compared to healthy newborns at the same postmenstrual age. We have measured evoked potentials generated by noxious clinically-essential heel lances in infants born at term (8 infants; born 37-40weeks) and in infants born prematurely (7 infants; born 24-32weeks) who had reached the same postmenstrual age (mean age at time of heel lance 39.2+/-1.2weeks). These noxious-evoked potentials are clearly distinguishable from shorter latency potentials evoked by non-noxious tactile sensory stimulation. While the shorter latency touch potentials are not dependent on the age of the infant at birth, the noxious-evoked potentials are significantly larger in prematurely-born infants. This enhancement is not associated with specific brain lesions but reflects a functional change in pain processing in the brain that is likely to underlie previously reported changes in pain sensitivity in older ex-preterm children. Our ability to quantify and measure experience-dependent changes in infant cortical pain processing will allow us to develop a more rational approach to pain management in neonatal intensive care. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Minoxidil sulfate induced the increase in blood-brain tumor barrier permeability through ROS/RhoA/PI3K/PKB signaling pathway.

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Gu, Yan-ting; Xue, Yi-xue; Wang, Yan-feng; Wang, Jin-hui; Chen, Xia; ShangGuan, Qian-ru; Lian, Yan; Zhong, Lei; Meng, Ying-nan

2013-12-01

Adenosine 5'-triphosphate-sensitive potassium channel (KATP channel) activator, minoxidil sulfate (MS), can selectively increase the permeability of the blood-tumor barrier (BTB); however, the mechanism by which this occurs is still under investigation. Using a rat brain glioma (C6) model, we first examined the expression levels of occludin and claudin-5 at different time points after intracarotid infusion of MS (30 μg/kg/min) by western blotting. Compared to MS treatment for 0 min group, the protein expression levels of occludin and claudin-5 in brain tumor tissue of rats showed no changes within 1 h and began to decrease significantly after 2 h of MS infusion. Based on these findings, we then used an in vitro BTB model and selective inhibitors of diverse signaling pathways to investigate whether reactive oxygen species (ROS)/RhoA/PI3K/PKB pathway play a key role in the process of the increase of BTB permeability induced by MS. The inhibitor of ROS or RhoA or PI3K or PKB significantly attenuated the expression of tight junction (TJ) protein and the increase of the BTB permeability after 2 h of MS treatment. In addition, the significant increases in RhoA activity and PKB phosphorylation after MS administration were observed, which were partly inhibited by N-2-mercaptopropionyl glycine (MPG) or C3 exoenzyme or LY294002 pretreatment. The present study indicates that the activation of signaling cascades involving ROS/RhoA/PI3K/PKB in BTB was required for the increase of BTB permeability induced by MS. Taken together, all of these results suggested that MS might increase BTB permeability in a time-dependent manner by down-regulating TJ protein expression and this effect could be related to ROS/RhoA/PI3K/PKB signal pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hemispheric lateralization of topological organization in structural brain networks.

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Caeyenberghs, Karen; Leemans, Alexander

2014-09-01

The study on structural brain asymmetries in healthy individuals plays an important role in our understanding of the factors that modulate cognitive specialization in the brain. Here, we used fiber tractography to reconstruct the left and right hemispheric networks of a large cohort of 346 healthy participants (20-86 years) and performed a graph theoretical analysis to investigate this brain laterality from a network perspective. Findings revealed that the left hemisphere is significantly more "efficient" than the right hemisphere, whereas the right hemisphere showed higher values of "betweenness centrality" and "small-worldness." In particular, left-hemispheric networks displayed increased nodal efficiency in brain regions related to language and motor actions, whereas the right hemisphere showed an increase in nodal efficiency in brain regions involved in memory and visuospatial attention. In addition, we found that hemispheric networks decrease in efficiency with age. Finally, we observed significant gender differences in measures of global connectivity. By analyzing the structural hemispheric brain networks, we have provided new insights into understanding the neuroanatomical basis of lateralized brain functions. Copyright © 2014 Wiley Periodicals, Inc.

Effect of AVP on brain edema following traumatic brain injury

Institute of Scientific and Technical Information of China (English)

XU Miao; SU Wei; HUANG Wei-dong; LU Yuan-qiang; XU Qiu-ping; CHEN Zhao-jun

2007-01-01

Objective: To evaluate plasma arginine vasopressin (AVP) level in patients with traumatic brain injury and investigate the role of AVP in the process of brain edema. Methods: A total of 30 patients with traumatic brain injury were involved in our study. They were divided into two groups by Glasgow Coma Scale: severe traumatic brain injury group (STBI, GCS≤ 8) and moderate traumatic brain injury group (MTBI, GCS＞8).Samples of venous blood were collected in the morning at rest from 15 healthy volunteers (control group)and within 24 h after traumatic brain injury from these patients for AVP determinations by radioimmunoassay. The severity and duration of the brain edema were estimated by head CT scan.Results: plasma AVP levels (ng/L) were (mean±SD): control, 3.06±1.49; MTBI, 38.12±7.25; and STBI, 66.61±17.10.The plasma level of AVP was significantly increased within 24 h after traumatic brain injury and followed by the reduction of GCS, suggesting the deterioration of cerebral injury (P＜0.01). And the AVP level was correlated with the severity (STBI r=0.919, P＜0.01; MTBI r=0.724, P＜0.01) and the duration of brain edema (STBI r=0.790, P＜0.01; MTBI r=0.712, P＜0.01). Conclusions: The plasma AVP level is closely associated with the severity of traumatic brain injury. AVP may play an important role in pathogenesis of brain edema after traumatic brain injury.

Brain structural connectivity increases concurrent with functional improvement: Evidence from diffusion tensor MRI in children with cerebral palsy during therapy

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Zoë A. Englander

2015-01-01

Full Text Available Cerebral Palsy (CP refers to a heterogeneous group of permanent but non-progressive movement disorders caused by injury to the developing fetal or infant brain (Bax et al., 2005. Because of its serious long-term consequences, effective interventions that can help improve motor function, independence, and quality of life are critically needed. Our ongoing longitudinal clinical trial to treat children with CP is specifically designed to meet this challenge. To maximize the potential for functional improvement, all children in this trial received autologous cord blood transfusions (with order randomized with a placebo administration over 2 years in conjunction with more standard physical and occupational therapies. As a part of this trial, magnetic resonance imaging (MRI is used to improve our understanding of how these interventions affect brain development, and to develop biomarkers of treatment efficacy. In this report, diffusion tensor imaging (DTI and subsequent brain connectome analyses were performed in a subset of children enrolled in the clinical trial (n = 17, who all exhibited positive but varying degrees of functional improvement over the first 2-year period of the study. Strong correlations between increases in white matter (WM connectivity and functional improvement were demonstrated; however no significant relationships between either of these factors with the age of the child at time of enrollment were identified. Thus, our data indicate that increases in brain connectivity reflect improved functional abilities in children with CP. In future work, this potential biomarker can be used to help differentiate the underlying mechanisms of functional improvement, as well as to identify treatments that can best facilitate functional improvement upon un-blinding of the timing of autologous cord blood transfusions at the completion of this study.

Brain structural connectivity increases concurrent with functional improvement: evidence from diffusion tensor MRI in children with cerebral palsy during therapy.

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Englander, Zoë A; Sun, Jessica; Laura Case; Mikati, Mohamad A; Kurtzberg, Joanne; Song, Allen W

2015-01-01

Cerebral Palsy (CP) refers to a heterogeneous group of permanent but non-progressive movement disorders caused by injury to the developing fetal or infant brain (Bax et al., 2005). Because of its serious long-term consequences, effective interventions that can help improve motor function, independence, and quality of life are critically needed. Our ongoing longitudinal clinical trial to treat children with CP is specifically designed to meet this challenge. To maximize the potential for functional improvement, all children in this trial received autologous cord blood transfusions (with order randomized with a placebo administration over 2 years) in conjunction with more standard physical and occupational therapies. As a part of this trial, magnetic resonance imaging (MRI) is used to improve our understanding of how these interventions affect brain development, and to develop biomarkers of treatment efficacy. In this report, diffusion tensor imaging (DTI) and subsequent brain connectome analyses were performed in a subset of children enrolled in the clinical trial (n = 17), who all exhibited positive but varying degrees of functional improvement over the first 2-year period of the study. Strong correlations between increases in white matter (WM) connectivity and functional improvement were demonstrated; however no significant relationships between either of these factors with the age of the child at time of enrollment were identified. Thus, our data indicate that increases in brain connectivity reflect improved functional abilities in children with CP. In future work, this potential biomarker can be used to help differentiate the underlying mechanisms of functional improvement, as well as to identify treatments that can best facilitate functional improvement upon un-blinding of the timing of autologous cord blood transfusions at the completion of this study.

A Link between the Increase in Electroencephalographic Coherence and Performance Improvement in Operating a Brain-Computer Interface

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Irma Nayeli Angulo-Sherman

2015-01-01

Full Text Available We study the relationship between electroencephalographic (EEG coherence and accuracy in operating a brain-computer interface (BCI. In our case, the BCI is controlled through motor imagery. Hence, a number of volunteers were trained using different training paradigms: classical visual feedback, auditory stimulation, and functional electrical stimulation (FES. After each training session, the volunteers’ accuracy in operating the BCI was assessed, and the event-related coherence (ErCoh was calculated for all possible combinations of pairs of EEG sensors. After at least four training sessions, we searched for significant differences in accuracy and ErCoh using one-way analysis of variance (ANOVA and multiple comparison tests. Our results show that there exists a high correlation between an increase in ErCoh and performance improvement, and this effect is mainly localized in the centrofrontal and centroparietal brain regions for the case of our motor imagery task. This result has a direct implication with the development of new techniques to evaluate BCI performance and the process of selecting a feedback modality that better enhances the volunteer’s capacity to operate a BCI system.

Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

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José Jaime Herrera-Pérez

2013-01-01

Full Text Available In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT expression associated with low testosterone (T levels. The objectives of this study were to establish (1 if brain SERT expression is reduced by aging and (2 if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population.

Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine

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Delp, M. D.; Armstrong, R. B.; Godfrey, D. A.; Laughlin, M. H.; Ross, C. D.; Wilkerson, M. K.

2001-01-01

1. The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (V(O(2),max)). 2. Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 % V(O(2),max), respectively. 3. Mean brain blood flow increased 24 and 25 % at 70 and 100 % V(O(2),max), respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. 4. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. 5. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis.

Increased expression of EMMPRIN and VEGF in the rat brain after gamma irradiation.

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Wei, Ming; Li, Hong; Huang, Huiling; Xu, Desheng; Zhi, Dashi; Liu, Dong; Zhang, Yipei

2012-03-01

The extracellular matrix metalloproteinase inducer (EMMPRIN) has been known to play a key regulatory role in pathological angiogenesis. A elevated activation of vascular endothelial growth factor (VEGF) following radiation injury has been shown to mediate blood-brain barrier (BBB) breakdown. However, the roles of EMMPRIN and VEGF in radiation-induced brain injury after gamma knife surgery (GKS) are not clearly understood. In this study, we investigated EMMPRIN changes in a rat model of radiation injury following GKS and examined potential associations between EMMPRIN and VEGF expression. Adult male rats were subjected to cerebral radiation injury by GKS under anesthesia. We found that EMMPRIN and VEGF expression were markedly upregulated in the target area at 8-12 weeks after GKS compared with the control group by western blot, immunohistochemistry, and RT-PCR analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals colocalized with caspase-3 and VEGF-positive cells. Our data also demonstrated that increased EMMPRIN expression was correlated with increased VEGF levels in a temporal manner. This is the first study to show that EMMPRIN and VEGF may play a role in radiation injuries of the central nervous system after GKS.

Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study

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2012-01-01

Background This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer’s disease (AD). Methods In a well-powered microarray study of young (20 to 59 years), aged (60 to 99 years), and AD (74 to 95 years) cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus. Results Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%). In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets), with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine) that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc) receptors and human leukocyte antigens I

Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study

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Cribbs David H

2012-07-01

Full Text Available Abstract Background This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer’s disease (AD. Methods In a well-powered microarray study of young (20 to 59 years, aged (60 to 99 years, and AD (74 to 95 years cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus. Results Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%. In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets, with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc receptors and human

Methylphenidate increases glucose uptake in the brain of young and adult rats.

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Réus, Gislaine Z; Scaini, Giselli; Titus, Stephanie E; Furlanetto, Camila B; Wessler, Leticia B; Ferreira, Gabriela K; Gonçalves, Cinara L; Jeremias, Gabriela C; Quevedo, João; Streck, Emilio L

2015-10-01

Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Increased brain natriuretic peptide as a marker for right ventricular dysfunction in acute pulmonary embolism

NARCIS (Netherlands)

Tulevski, I. I.; Hirsch, A.; Sanson, B. J.; Romkes, H.; van der Wall, E. E.; van Veldhuisen, D. J.; Büller, H. R.; Mulder, B. J.

2001-01-01

Right ventricular (RV) function is of major prognostic significance in patients with acute pulmonary embolism (PE). The aim of the present study was to evaluate the role of neurohormone plasma brain natriuretic peptide (BNP) in assessing RV function in patients with acute PE. BNP levels were

Increased brain natriuretic peptide as a marker for right ventricular dysfunction in acute pulmonary embolism

NARCIS (Netherlands)

Tulevski, I.I.; Hirsch, A; Sanson, BJ; Romkes, H; van der Wall, EE; van Veldhuisen, DJ; Buller, HR; Mulder, BJM

Right ventricular (RV) function is of major prognostic significance in patients with acute pulmonary embolism (PE). The aim of the present study was to evaluate the role of neurohormone plasma brain natriuretic peptide (BNP) in assessing RV function in patients with acute PE. BNP levels were

Absence of PO2 change in fetal brain despite PO2 increase in placenta in response to maternal oxygen challenge.

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Huen, I; Morris, D M; Wright, C; Sibley, C P; Naish, J H; Johnstone, E D

2014-12-01

Magnetic resonance imaging allows the noninvasive observation of PO2 changes between air breathing and oxygen breathing through quantification of the magnetic longitudinal relaxation time T1. Changes in PO2 are proportional to changes in the longitudinal relaxation rate ΔR1 (where ΔR1=1/T1oxygen-1/T1air). Knowledge of this response could inform clinical interventions using maternal oxygen administration antenatally to treat fetal growth restriction. We present in vivo measurements of the response of the fetal-placental unit to maternal hyperoxia. Prospective cohort. Large tertiary maternity hospital. Nine women undergoing low-risk pregnancy (21-33 weeks of gestation) and five nonpregnant adults. During imaging the air supply to mothers was changed from medical air (21% oxygen) to medical oxygen (100% oxygen) and T1 was monitored over time in both the placenta and fetal brain using a periodically repeated magnetic resonance imaging sequence. To demonstrate that the method could detect a brain response, brain responses from five normal adult volunteers were measured using a similar imaging protocol. Changes in T1 following oxygen challenge. No significant ΔR1 (P=0.42, paired t-test) was observed in fetal brains. A significant placental ΔR1 (P=0.0002, paired t-test) of 0.02±0.01/s (mean±SD) was simultaneously observed in the same participants. In the brains of the nonpregnant adults, a significant ΔR1 (P=0.01, paired t-test) of 0.005±0.002/s was observed. Short-term maternal oxygen administration does not improve fetal brain oxygenation, in contrast to the response observed in the adult brain. © 2014 Royal College of Obstetricians and Gynaecologists.

Metabolic drift in the aging brain.

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Ivanisevic, Julijana; Stauch, Kelly L; Petrascheck, Michael; Benton, H Paul; Epstein, Adrian A; Fang, Mingliang; Gorantla, Santhi; Tran, Minerva; Hoang, Linh; Kurczy, Michael E; Boska, Michael D; Gendelman, Howard E; Fox, Howard S; Siuzdak, Gary

2016-05-01

Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication.

Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy.

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Tam, Emily W Y; Haeusslein, Laurel A; Bonifacio, Sonia L; Glass, Hannah C; Rogers, Elizabeth E; Jeremy, Rita J; Barkovich, A James; Ferriero, Donna M

2012-07-01

To investigate the contribution of hypoglycemia in the first 24 hours after birth to brain injury in term newborns at risk for neonatal encephalopathy. A prospective cohort of 94 term neonates born between 1994 and 2010 with early postnatal brain magnetic resonance imaging studies were analyzed for regions of brain injury. Neurodevelopmental outcome was assessed at 1 year of age. Hypoglycemia (glucose encephalopathy with increased corticospinal tract injury and adverse motor and cognitive outcomes. Copyright © 2012 Mosby, Inc. All rights reserved.

Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

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Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

2015-12-01

The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Analysis of Brain Recurrence

Science.gov (United States)

Frilot, Clifton; Kim, Paul Y.; Carrubba, Simona; McCarty, David E.; Chesson, Andrew L.; Marino, Andrew A.

Analysis of Brain Recurrence (ABR) is a method for extracting physiologically significant information from the electroencephalogram (EEG), a non-stationary electrical output of the brain, the ultimate complex dynamical system. ABR permits quantification of temporal patterns in the EEG produced by the non-autonomous differential laws that govern brain metabolism. In the context of appropriate experimental and statistical designs, ABR is ideally suited to the task of interpreting the EEG. Present applications of ABR include discovery of a human magnetic sense, increased mechanistic understanding of neuronal membrane processes, diagnosis of degenerative neurological disease, detection of changes in brain metabolism caused by weak environmental electromagnetic fields, objective characterization of the quality of human sleep, and evaluation of sleep disorders. ABR has important beneficial implications for the development of clinical and experimental neuroscience.

Neuroenergetics: How energy constraints shape brain function

CERN Multimedia

CERN. Geneva

2016-01-01

The nervous system consumes a disproportionate fraction of the resting body’s energy production. In humans, the brain represents 2% of the body’s mass, yet it accounts for ~20% of the total oxygen consumption. Expansion in the size of the brain relative to the body and an increase in the number of connections between neurons during evolution underpin our cognitive powers and are responsible for our brains’ high metabolic rate. The molecules at the center of cellular energy metabolism also act as intercellular signals and constitute an important communication pathway, coordinating for instance the immune surveillance of the brain. Despite the significance of energy consumption in the nervous system, how energy constrains and shapes brain function is often under appreciated. I will illustrate the importance of brain energetics and metabolism with two examples from my recent work. First, I will show how the brain trades information for energy savings in the visual pathway. Indeed, a significant fraction ...

Increased brain dopamine and dopamine receptors in schizophrenia

International Nuclear Information System (INIS)

Mackay, A.V.; Iversen, L.L.; Rossor, M.; Spokes, E.; Bird, E.; Arregui, A.; Creese, I.; Synder, S.H.

1982-01-01

In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone. The increase in apparent KD probably reflects the presence of residual neuroleptic drugs, but changes in Bmax for tritiated spiperone reflect genuine changes in receptor numbers. The increases in receptors were seen only in patients in whom neuroleptic medication had been maintained until the time of death, indicating that they may be entirely iatrogenic. Dopamine measurements for a larger series of schizophrenic and control cases (n greater than 60) show significantly increased concentrations in both the nucleus accumbens and caudate nucleus. The changes in dopamine were not obviously related to neuroleptic medication and, unlike the receptor changes, were most severe in younger patients

Binge consumption of ethanol during pregnancy leads to significant developmental delay of mouse embryonic brain

Science.gov (United States)

Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

2014-03-01

Consumption of alcohol during pregnancy can be severely detrimental to the development of the brain in fetuses. This study explores the usage of optical coherence tomography (OCT) to the study the effects of maternal consumption of ethanol on brain development in mouse fetuses. On gestational day 14.5, fetuses were collected and fixed in 4% paraformaldehyde. A swept-source OCT (SSOCT) system was used to acquire 3D images of the brain of ethanol-exposed and control fetuses. The volume of right and left brain ventricles were measured and used to compare between ethanol-exposed and control fetuses. A total of 5 fetuses were used for each of the two groups. The average volumes of the right and left ventricles were measured to be 0.35 and 0.15 mm3 for ethanol-exposed and control fetuses, respectively. The results demonstrated that there is an alcohol-induced developmental delay in mouse fetal brains.

Relationship between changes of N-methyl-D-aspartate receptor activity and brain edema after brain injury in rats

Institute of Scientific and Technical Information of China (English)

无

2001-01-01

Objective:　To investigate the relationship between the changes of N-methyl-D-aspartate (NMDA) receptor activity and brain edema after injury in rats. 　　Methods:　The brain injury models were made by using a free-falling body. The treatment model was induced by means of injecting AP5 into lateral ventricle before brain injury; water contents in brain cortex were measured with dry-wet method; and NMDA receptor activity was detected with a radio ligand binding assay. 　　Results:　The water contents began to increase at 30 minutes and reached the peak at 6 hours after brain injury. The maximal binding (Bmax) of NMDA receptor increased significantly at 15 minutes and reached the peak at 30 minutes, then decreased gradually and had the lowest value 6 hours after brain injury. Followed the treatment with AP5, NMDA receptor activity in the injured brain showed a normal value; and the water contents were lower than that of AP5-free injury group 24 hours after brain injury. 　　Conclusions:　It suggests that excessive activation of NMDA receptor may be one of the most important factors to induce the secondary cerebral impairments, and AP5 may protect the brain from edema after brain injury.

Viewing the functional consequences of traumatic brain injury by using brain SPECT.

Science.gov (United States)

Pavel, D; Jobe, T; Devore-Best, S; Davis, G; Epstein, P; Sinha, S; Kohn, R; Craita, I; Liu, P; Chang, Y

2006-03-01

High-resolution brain SPECT is increasingly benefiting from improved image processing software and multiple complementary display capabilities. This enables detailed functional mapping of the disturbances in relative perfusion occurring after TBI. The patient population consisted of 26 cases (ages 8-61 years)between 3 months and 6 years after traumatic brain injury.A very strong case can be made for the routine use of Brain SPECT in TBI. Indeed it can provide a detailed evaluation of multiple functional consequences after TBI and is thus capable of supplementing the clinical evaluation and tailoring the therapeutic strategies needed. In so doing it also provides significant additional information beyond that available from MRI/CT. The critical factor for Brain SPECT's clinical relevance is a carefully designed technical protocol, including displays which should enable a comprehensive description of the patterns found, in a user friendly mode.

Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors.

Directory of Open Access Journals (Sweden)

Elizabeth Harford-Wright

Full Text Available The neuropeptide substance P (SP has been implicated in the disruption of the blood-brain barrier (BBB and development of cerebral edema in acute brain injury. Cerebral edema accumulates rapidly around brain tumors and has been linked to several tumor-associated deficits. Currently, the standard treatment for peritumoral edema is the corticosteroid dexamethasone, prolonged use of which is associated with a number of deleterious side effects. As SP is reported to increase in many cancer types, this study examined whether SP plays a role in the genesis of brain peritumoral edema. A-375 human melanoma cells were injected into the right striatum of male Balb/c nude mice to induce brain tumor growth, with culture medium injected in animals serving as controls. At 2, 3 or 4 weeks following tumor cell inoculation, non-treated animals were perfusion fixed for immunohistochemical detection of Albumin, SP and NK1 receptor. A further subgroup of animals was treated with a daily injection of the NK1 antagonist Emend (3 mg/kg, dexamethasone (8 mg/kg or saline vehicle at 3 weeks post-inoculation. Animals were sacrificed a week later to determine BBB permeability using Evan's Blue and brain water content. Non-treated animals demonstrated a significant increase in albumin, SP and NK1 receptor immunoreactivity in the peritumoral area as well as increased perivascular staining in the surrounding brain tissue. Brain water content and BBB permeability was significantly increased in tumor-inoculated animals when compared to controls (p<0.05. Treatment with Emend and dexamethasone reduced BBB permeability and brain water content when compared to vehicle-treated tumor-inoculated mice. The increase in peritumoral staining for both SP and the NK1 receptor, coupled with the reduction in brain water content and BBB permeability seen following treatment with the NK1 antagonist Emend, suggests that SP plays a role in the genesis of peritumoral edema, and thus warrants

Changes in brain size during the menstrual cycle.

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Georg Hagemann

Full Text Available BACKGROUND: There is increasing evidence for hormone-dependent modification of function and behavior during the menstrual cycle, but little is known about associated short-term structural alterations of the brain. Preliminary studies suggest that a hormone-dependent decline in brain volume occurs in postmenopausal, or women receiving antiestrogens, long term. Advances in serial MR-volumetry have allowed for the accurate detection of small volume changes of the brain. Recently, activity-induced short-term structural plasticity of the brain was demonstrated, challenging the view that the brain is as rigid as formerly believed. METHODOLOGY/PRINCIPAL FINDINGS: We used MR-volumetry to investigate short-term brain volume changes across the menstrual cycle in women or a parallel 4 week period in men, respectively. We found a significant grey matter volume peak and CSF loss at the time of ovulation in females. This volume peak did not correlate with estradiol or progesterone hormone levels. Men did not show any significant brain volume alterations. CONCLUSIONS/SIGNIFICANCE: These data give evidence of short-term hormone-dependent structural brain changes during the menstrual cycle, which need to be correlated with functional states and have to be considered in structure-associated functional brain research.

Short-term exposure of mice to gasoline vapor increases the metallothionein expression in the brain, lungs and kidney.

Science.gov (United States)

Grebić, D; Jakovac, H; Mrakovcić-Sutić, I; Tomac, J; Bulog, A; Micović, V; Radosević-Stasić, B

2007-06-01

Environmental airborne pollution has been repeatedly shown to affect multiple aspects of brain and cardiopulmonary function, leading to cognitive and behavioral changes and to the pronounced inflammatory response in the respiratory airways. Since in the cellular defense system the important role might have stress proteins-metallothionein (MT)-I and MT-II, which are involved in sequestration and dispersal of metal ions, regulation of the biosynthesis and activities of zinc-dependent transcription factors, as well as in cellular protection from reactive oxygen species, genotoxicity and apoptosis, in this study we investigated their expression in the brain, lungs and kidney, following intermittent exposure of mice to gasoline vapor. Control groups consisted of intact mice and of those closed in the metabolic chamber and ventilated with fresh air. The data obtained by immunohistochemistry showed that gasoline inhalation markedly upregulated the MTs expression in tissues which were directly or indirectly exposed to toxic components, significantly increasing the number of MT I+II positive cells in CNS (the entorhinal cortex, ependymal cells, astroglial cells in subventricular zone and inside the brain parenchyma, subgranular and CA1-CA3 zone of the dentate gyrus in hippocampus and macrophages-like cells in perivascular spaces), in the lungs (pneumocytes type I and type II) and in the kidneys (parietal wall of Bowman capsule, proximal and distal tubules). The data point to the protective and growth-regulatory effects of MT I + II on places of injuries, induced by inhalation of gasoline vapor.

Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis.

Science.gov (United States)

Kappus, Natalie; Weinstock-Guttman, Bianca; Hagemeier, Jesper; Kennedy, Cheryl; Melia, Rebecca; Carl, Ellen; Ramasamy, Deepa P; Cherneva, Mariya; Durfee, Jacqueline; Bergsland, Niels; Dwyer, Michael G; Kolb, Channa; Hojnacki, David; Ramanathan, Murali; Zivadinov, Robert

2016-02-01

Cardiovascular (CV) risk factors have been associated with changes in clinical outcomes in patients with multiple sclerosis (MS). To investigate the frequency of CV risks in patients with MS and their association with MRI outcomes. In a prospective study, 326 patients with relapsing-remitting MS and 163 patients with progressive MS, 61 patients with clinically isolated syndrome (CIS) and 175 healthy controls (HCs) were screened for CV risks and scanned on a 3T MRI scanner. Examined CV risks included hypertension, heart disease, smoking, overweight/obesity and type 1 diabetes. MRI measures assessed lesion volumes (LVs) and brain atrophy. Association between individual or multiple CV risks and MRI outcomes was examined adjusting for age, sex, race, disease duration and treatment status. Patients with MS showed increased frequency of smoking (51.7% vs 36.5%, p = 0.001) and hypertension (33.9% vs 24.7%, p=0.035) compared with HCs. In total, 49.9% of patients with MS and 36% of HCs showed ≥ 2 CV risks (p = 0.003), while the frequency of ≥ 3 CV risks was 18.8% in the MS group and 8.6% in the HCs group (p = 0.002). In patients with MS, hypertension and heart disease were associated with decreased grey matter (GM) and cortical volumes (p < 0.05), while overweight/obesity was associated with increased T1-LV (p < 0.39) and smoking with decreased whole brain volume (p = 0.049). Increased lateral ventricle volume was associated with heart disease (p = 0.029) in CIS. Patients with MS with one or more CV risks showed increased lesion burden and more advanced brain atrophy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Brain volume reduction after whole-brain radiotherapy: quantification and prognostic relevance.

Science.gov (United States)

Hoffmann, Christian; Distel, Luitpold; Knippen, Stefan; Gryc, Thomas; Schmidt, Manuel Alexander; Fietkau, Rainer; Putz, Florian

2018-01-22

Recent studies have questioned the value of adding whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) for brain metastasis treatment. Neurotoxicity, including radiation-induced brain volume reduction, could be one reason why not all patients benefit from the addition of WBRT. In this study, we quantified brain volume reduction after WBRT and assessed its prognostic significance. Brain volumes of 91 patients with cerebral metastases were measured during a 150-day period after commencing WBRT and were compared with their pretreatment volumes. The average daily relative change in brain volume of each patient, referred to as the "brain volume reduction rate," was calculated. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of the brain volume reduction rate, as well as of 3 treatment-related and 9 pretreatment factors. A one-way analysis of variance was used to compare the brain volume reduction rate across recursive partitioning analysis (RPA) classes. On multivariate Cox regression analysis, the brain volume reduction rate was a significant predictor of overall survival after WBRT (P < 0.001), as well as the number of brain metastases (P = 0.002) and age (P = 0.008). Patients with a relatively favorable prognosis (RPA classes 1 and 2) experienced significantly less brain volume decrease after WBRT than patients with a poor prognosis (RPA class 3) (P = 0.001). There was no significant correlation between delivered radiation dose and brain volume reduction rate (P = 0.147). In this retrospective study, a smaller decrease in brain volume after WBRT was an independent predictor of longer overall survival. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Significant changes in the amounts of neurotransmitter and related substances in rat brain induced by subacute exposure to low levels of toluene and xylene

Energy Technology Data Exchange (ETDEWEB)

Honma, T.; Sudo, A.; Miyagawa, M.; Sato, M.; Hasegawa, H.

1983-01-01

Rats were exposed to toluene and xylene at 200-800 ppm for 30 days. After exposure, changes in the dopamine, norepinephrine, serotonin, acetylcholine (ACh), cyclic AMP, cyclic GMP, GABA, glutamic acid, glutamine, aspartic acid, taurine, glycine and alanine content of different areas of the brain were investigated. ACh in the striatum and whole brain were reduced dose-dependently by toluene and xylene. The reduction at 800 ppm of the solvents was in the range of 10 to 20% of the ACh content of the control rats. Toluene and xylene caused different changes in monoamine content other than ACh, but the changes were not dose-dependent. Among the seven free amino acids that are the main amino acid components of the brain, the glutamine content was increased by toluene and xylene at 800 ppm. Decrease in ACh and increase in glutamine in the brain appear to be phenomena common to many kinds of organic solvents including toluene and xylene after acute and subacute exposure.

Chronic pyruvate supplementation increases exploratory activity and brain energy reserves in young and middle-aged mice

Directory of Open Access Journals (Sweden)

Hennariikka eKoivisto

2016-03-01

Full Text Available Numerous studies have reported neuroprotective effects of pyruvate when given in systemic injections. Impaired glucose uptake and metabolism are found in Alzheimer's disease (AD and in AD mouse models. We tested whether dietary pyruvate supplementation is able to provide added energy supply to brain and thereby attenuate aging- or AD-related cognitive impairment. Mice received ~ 800 mg/kg/day Na-pyruvate in their chow for 2- 6 months. In middle-aged wild-type mice and in 6.5-month-old APP/PS1 mice, pyruvate facilitated spatial learning and increased exploration of a novel odor. However, in passive avoidance task for fear memory, the treatment group was clearly impaired. Independent of age, long-term pyruvate increased explorative behavior, which likely explains the paradoxical impairment in passive avoidance. We also assessed pyruvate effects on body weight, muscle force and endurance, and found no effects. Metabolic post-mortem assays revealed increased energy compounds in nuclear magnetic resonance spectroscopy as well as increased brain glycogen storages in the pyruvate group. Pyruvate supplementation may counteract aging-related behavioral impairment but its beneficial effect seems related to increased explorative activity rather than direct memory enhancement.

Significance of Lead Residues in Mallard Tissues

Science.gov (United States)

Longcore, J.R.; Locke, L.N.; Bagley, George E.; Andrews, R.

1974-01-01

Tissues of adult, lead-dosed mallards that either died or were sacrificed were analyzed for lead. Lead levels in brains, tibiae, and breast muscle of ducks that died and in tibiae of ducks that were sacrificed increased significantly from dosage until death. Lead in the heart, lung, and blood from sacrificed ducks decreased significantly from dosage until death. Lead concentrations in tissues from ducks in the two groups were not significantly different except for the liver, kidney, and lung. Average lead levels in the livers and kidneys of ducks that died were significantly higher than those in ducks that were sacrificed. The mean concentration of lead in the lungs of the ducks sacrificed was significantly higher than the mean level in the lungs of ducks that died. Measurements of the lead concentrations in this study, when compared with lead levels reported in the literature for avian and non-avian species, showed that arbitrary diagnostic levels indicating lead poisoning could be set. In mallard ducks, lead levels exceeding 3 ppm in the brain, 6 to 20 ppm in the kidney or liver, or 10 ppm in clotted blood from the heart indicated acute exposure to lead.

Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality.

Science.gov (United States)

Burman, P; Mattsson, A F; Johannsson, G; Höybye, C; Holmer, H; Dahlqvist, P; Berinder, K; Engström, B E; Ekman, B; Erfurth, E M; Svensson, J; Wahlberg, J; Karlsson, F A

2013-04-01

Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified. To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up. All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed. Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up. An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy. Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

A family of hyperelastic models for human brain tissue

Science.gov (United States)

Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

2017-09-01

Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

Increased Working Memory-Related Brain Activity in Middle-Aged Women with Cognitive Complaints

OpenAIRE

Dumas, Julie A.; Kutz, Amanda M.; McDonald, Brenna C.; R.Naylor, Magdalena; Pfaff, Ashley C.; Saykin, Andrew J.; Newhouse, Paul A.

2012-01-01

Individuals who report subjective cognitive complaints but perform normally on neuropsychological tests may be at increased risk for pathological cognitive aging. The current study examined the effects of the presence of subjective cognitive complaints on functional brain activity during a working memory task in a sample of middle-aged postmenopausal women. Twenty-three postmenopausal women aged 50–60 completed a cognitive complaint battery of questionnaires. Using 20% of items endorsed as th...

Thyroxin treatment protects against white matter injury in the immature brain via brain-derived neurotrophic factor.

Science.gov (United States)

Hung, Pi-Lien; Huang, Chao-Ching; Huang, Hsiu-Mei; Tu, Dom-Gene; Chang, Ying-Chao

2013-08-01

Low level of thyroid hormone is a strong independent risk factor for white matter (WM) injury, a major cause of cerebral palsy, in preterm infants. Thyroxin upregulates brain-derived neurotrophic factor during development. We hypothesized that thyroxin protected against preoligodendrocyte apoptosis and WM injury in the immature brain via upregulation of brain-derived neurotrophic factor. Postpartum (P) day-7 male rat pups were exposed to hypoxic ischemia (HI) and intraperitoneally injected with thyroxin (T4; 0.2 mg/kg or 1 mg/kg) or normal saline immediately after HI at P9 and P11. WM damage was analyzed for myelin formation, axonal injury, astrogliosis, and preoligodendrocyte apoptosis. Neurotrophic factor expression was assessed by real-time polymerase chain reaction and immunohistochemistry. Neuromotor functions were measured using open-field locomotion (P11 and P21), inclined plane climbing (P11), and beam walking (P21). Intracerebroventricular injection of TrkB-Fc or systemic administration of 7,8-dihydroxyflavone was performed. On P11, the HI group had significantly lower blood T4 levels than the controls. The HI group showed ventriculomegaly and marked reduction of myelin basic protein immunoreactivities in the WM. T4 (1 mg/kg) treatment after HI markedly attenuated axonal injury, astrocytosis, and microgliosis, and increased preoligodendrocyte survival. In addition, T4 treatment significantly increased myelination and selectively upregulated brain-derived neurotrophic factor expression in the WM, and improved neuromotor deficits after HI. The protective effect of T4 on WM myelination and neuromotor performance after HI was significantly attenuated by TrkB-Fc. Systemic 7,8-dihydroxyflavone treatment ameliorated hypomyelination after HI injury. T4 protects against WM injury at both pathological and functional levels via upregulation of brain-derived neurotrophic factor-TrkB signaling in the immature brain.

CCK increases the transport of insulin into the brain.

Science.gov (United States)

May, Aaron A; Liu, Min; Woods, Stephen C; Begg, Denovan P

2016-10-15

Food intake occurs in bouts or meals, and numerous meal-generated signals have been identified that act to limit the size of ongoing meals. Hormones such as cholecystokinin (CCK) are secreted from the intestine as ingested food is being processed, and in addition to aiding the digestive process, they provide a signal to the brain that contributes to satiation, limiting the size of the meal. The potency of CCK to elicit satiation is enhanced by elevated levels of adiposity signals such as insulin. In the present experiments we asked whether CCK and insulin interact at the level of the blood-brain barrier (BBB). We first isolated rat brain capillary endothelial cells that comprise the BBB and found that they express the mRNA for both the CCK1R and the insulin receptor, providing a basis for a possible interaction. We then administered insulin intraperitoneally to another group of rats and 15min later administered CCK-8 intraperitoneally to half of those rats. After another 15min, CSF and blood samples were obtained and assayed for immunoreactive insulin. Plasma insulin was comparably elevated above baseline in both the CCK-8 and control groups, indicating that the CCK had no effect on circulating insulin levels given these parameters. In contrast, rats administered CCK had CSF-insulin levels that were more than twice as high as those of control rats. We conclude that circulating CCK greatly facilitates the transport of insulin into the brain, likely by acting directly at the BBB. These findings imply that in circumstances in which the plasma levels of both CCK and insulin are elevated, such as during and soon after meals, satiation is likely to be due, in part, to this newly-discovered synergy between CCK and insulin. Copyright © 2016 Elsevier Inc. All rights reserved.

Deep Brain Stimulation Target Selection in an Advanced Parkinson's Disease Patient with Significant Tremor and Comorbid Depression

Directory of Open Access Journals (Sweden)

Amar S. Patel

2017-04-01

Full Text Available Clinical Vignette: A 67-year-old female with advanced Parkinson's disease (PD, medically refractory tremor, and a history of significant depression presents for evaluation of deep brain stimulation (DBS candidacy.  Clinical Dilemma: Traditionally, stimulation of the subthalamic nucleus (STN has been the preferred target for patients with significant PD tremor. However, STN stimulation is avoided in patients with a significant pre-surgical history of mood disorder.  Clinical Solution: Bilateral DBS of the globus pallidus interna led to significant short term improvement in PD motor symptoms, including significant tremor reduction.  Gap in Knowledge: There is insufficient evidence to support or refute clinicians' traditional preference for STN stimulation in treating refractory PD tremor. Similarly, the available evidence for risk of worsening depression and/or suicidality after STN DBS is mixed. Both questions require further clarification to guide patient and clinician decision-making.

Apolipoprotein E Mimetic Peptide Increases Cerebral Glucose Uptake by Reducing Blood-Brain Barrier Disruption after Controlled Cortical Impact in Mice: An 18F-Fluorodeoxyglucose PET/CT Study.

Science.gov (United States)

Qin, Xinghu; You, Hong; Cao, Fang; Wu, Yue; Peng, Jianhua; Pang, Jinwei; Xu, Hong; Chen, Yue; Chen, Ligang; Vitek, Michael P; Li, Fengqiao; Sun, Xiaochuan; Jiang, Yong

2017-02-15

Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and reduces cerebral glucose uptake. Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI, and COG1410 has demonstrated neuroprotective activity in several models of TBI. However, the effects of COG1410 on VEGF and glucose metabolism following TBI are unknown. The current study aimed to investigate the expression of VEGF and glucose metabolism effects in C57BL/6J male mice subjected to experimental TBI. The results showed that controlled cortical impact (CCI)-induced vestibulomotor deficits were accompanied by increases in brain edema and the expression of VEGF, with a decrease in cerebral glucose uptake. COG1410 treatment significantly improved vestibulomotor deficits and glucose uptake and produced decreases in VEGF in the pericontusion and ipsilateral hemisphere of injury, as well as in brain edema and neuronal degeneration compared with the control group. These data support that COG1410 may have potential as an effective drug therapy for TBI.

Antecedent control in the treatment of brain-injured clients.

Science.gov (United States)

Zencius, A H; Wesolowski, M D; Burke, W H; McQuade, P

1989-01-01

Three brain-injured clients failed to respond significantly to consequence management programmes designed to increase attendance, use of a cane, and to reduce unauthorized breaks. When antecedent stimulus control procedures were applied, attendance and use of a cane increased and unauthorized breaks decreased. The study shows that antecedent control may be the treatment of choice when treating brain-injured clients with memory loss.

Effect of increasing diffusion gradient direction number on diffusion tensor imaging fiber tracking in the human brain

International Nuclear Information System (INIS)

Yao, Xu Fang; Liang, Bie Bei; Xia, Tian; Huang, Qin Ming; Zhuang, Song Lin; Yu, Tong Gang

2015-01-01

To assess the effects of varying the number of diffusion gradient directions (NDGDs) on diffusion tensor fiber tracking (FT) in human brain white matter using tract characteristics. Twelve normal volunteers underwent diffusion tensor imaging (DTI) scanning with NDGDs of 6, 11, 15, 21, and 31 orientations. Three fiber tract groups, including the splenium of the corpus callosum (CC), the entire CC, and the full brain tract, were reconstructed by deterministic DTI-FT. Tract architecture was first qualitatively evaluated by visual observation. Six quantitative tract characteristics, including the number of fibers (NF), average length (AL), fractional anisotropy (FA), relative anisotropy (RA), mean diffusivity (MD), and volume ratio (VR) were measured for the splenium of the CC at the tract branch level, for the entire CC at tract level, and for the full brain tract at the whole brain level. Visual results and those of NF, AL, FA, RA, MD, and VR were compared among the five different NDGDs. The DTI-FT with NDGD of 11, 15, 21, and 31 orientations gave better tracking results compared with NDGD of 6 after the visual evaluation. NF, FA, RA, MD, and VR values with NDGD of six were significantly greater (smallest p = 0.001 to largest p = 0.042) than those with four other NDGDs (11, 15, 21, or 31 orientations), whereas AL measured with NDGD of six was significantly smaller (smallest p = 0.001 to largest p = 0.041) than with four other NDGDs (11, 15, 21, or 31 orientations). No significant differences were observed in the results among the four NDGD groups of 11, 15, 21, and 31 directions (smallest p = 0.059 to largest p = 1.000). The main fiber tracts were detected with NDGD of six orientations; however, the use of larger NDGD (> or = 11 orientations) could provide improved tract characteristics at the expense of longer scanning time.

Effect of increasing diffusion gradient direction number on diffusion tensor imaging fiber tracking in the human brain

Energy Technology Data Exchange (ETDEWEB)

Yao, Xu Fang; Liang, Bie Bei; Xia, Tian; Huang, Qin Ming; Zhuang, Song Lin [School of Optical-Electrical and Computer Engineering, Shanghai Medical Instrument College, University of Shanghai for Science and Technology, Shanghai (China); Yu, Tong Gang [Dept. of Radiology, Huashan Hospital, Fudan University, Shanghai (China)

2015-04-15

To assess the effects of varying the number of diffusion gradient directions (NDGDs) on diffusion tensor fiber tracking (FT) in human brain white matter using tract characteristics. Twelve normal volunteers underwent diffusion tensor imaging (DTI) scanning with NDGDs of 6, 11, 15, 21, and 31 orientations. Three fiber tract groups, including the splenium of the corpus callosum (CC), the entire CC, and the full brain tract, were reconstructed by deterministic DTI-FT. Tract architecture was first qualitatively evaluated by visual observation. Six quantitative tract characteristics, including the number of fibers (NF), average length (AL), fractional anisotropy (FA), relative anisotropy (RA), mean diffusivity (MD), and volume ratio (VR) were measured for the splenium of the CC at the tract branch level, for the entire CC at tract level, and for the full brain tract at the whole brain level. Visual results and those of NF, AL, FA, RA, MD, and VR were compared among the five different NDGDs. The DTI-FT with NDGD of 11, 15, 21, and 31 orientations gave better tracking results compared with NDGD of 6 after the visual evaluation. NF, FA, RA, MD, and VR values with NDGD of six were significantly greater (smallest p = 0.001 to largest p = 0.042) than those with four other NDGDs (11, 15, 21, or 31 orientations), whereas AL measured with NDGD of six was significantly smaller (smallest p = 0.001 to largest p = 0.041) than with four other NDGDs (11, 15, 21, or 31 orientations). No significant differences were observed in the results among the four NDGD groups of 11, 15, 21, and 31 directions (smallest p = 0.059 to largest p = 1.000). The main fiber tracts were detected with NDGD of six orientations; however, the use of larger NDGD (> or = 11 orientations) could provide improved tract characteristics at the expense of longer scanning time.

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

International Nuclear Information System (INIS)

Park, C. H.; Lim, S. Y.; Lee, I. Y.; Kim, O. H.; Bai, M. S.; Kim, S. J.; Yoon, S. N.; Cho, C. W.

1997-01-01

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 ( 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

Contribution of thrombin-reactive brain pericytes to blood-brain barrier dysfunction in an in vivo mouse model of obesity-associated diabetes and an in vitro rat model.

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Takashi Machida

Full Text Available Diabetic complications are characterized by the dysfunction of pericytes located around microvascular endothelial cells. The blood-brain barrier (BBB exhibits hyperpermeability with progression of diabetes. Therefore, brain pericytes at the BBB may be involved in diabetic complications of the central nervous system (CNS. We hypothesized that brain pericytes respond to increased brain thrombin levels in diabetes, leading to BBB dysfunction and diabetic CNS complications. Mice were fed a high-fat diet (HFD for 2 or 8 weeks to induce obesity. Transport of i.v.-administered sodium fluorescein and 125I-thrombin across the BBB were measured. We evaluated brain endothelial permeability and expression of tight junction proteins in the presence of thrombin-treated brain pericytes using a BBB model of co-cultured rat brain endothelial cells and pericytes. Mice fed a HFD for 8 weeks showed both increased weight gain and impaired glucose tolerance. In parallel, the brain influx rate of sodium fluorescein was significantly greater than that in mice fed a normal diet. HFD feeding inhibited the decline in brain thrombin levels occurring during 6 weeks of feeding. In the HFD fed mice, plasma thrombin levels were significantly increased, by up to 22%. 125I-thrombin was transported across the BBB in normal mice after i.v. injection, with uptake further enhanced by co-injection of unlabeled thrombin. Thrombin-treated brain pericytes increased brain endothelial permeability and caused decreased expression of zona occludens-1 (ZO-1 and occludin and morphological disorganization of ZO-1. Thrombin also increased mRNA expression of interleukin-1β and 6 and tumor necrosis factor-α in brain pericytes. Thrombin can be transported from circulating blood through the BBB, maintaining constant levels in the brain, where it can stimulate pericytes to induce BBB dysfunction. Thus, the brain pericyte-thrombin interaction may play a key role in causing BBB dysfunction in

Potential for increasing conspicuity of short-T1 lesions in the brain using magnetisation transfer imaging

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De Souza, N.M.; Hajnal, J.V.; Baudouin, C.J.

1995-01-01

We investigated the feasibility of using T1-weighted magnetisation transfer sequences to generate tissue contrast and increase the conspicuity of short-T1 areas within the brain. We imaged two normal volunteers with and without saturating off-resonance radiofrequency irradiation at a range of repetition times (TR 200-760 ms). T1 values and magnetisation transfer ratios for white matter and deep grey matter were calculated. We studied eight patients with intracranial lesions showing short-T1 areas, using mildly T1-weighted sequences with and without magnetisation transfer contrast. Lesion numbers, areas and signal intensities were measured and lesion-to-background contrast was calculated. Comparison was made with conventional T1-weighted spin-echo images. In the normal volunteers, contrast between the thalamus, caudate and lentiform nuclei and white matter showed striking visual differences, with magnetisation transfer weighting, with decreasing TR. In all patients, short-T1 lesions were seen more clearly on magnetisation transfer-weighted images, with significant increase in lesion number, area and contrast, when compared with conventional T1-weighted scans. (orig.)

Long-term treatment with peony glycosides reverses chronic unpredictable mild stress-induced depressive-like behavior via increasing expression of neurotrophins in rat brain.

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Mao, Qing-Qiu; Xian, Yan-Fang; Ip, Siu-Po; Tsai, Sam-Hip; Che, Chun-Tao

2010-07-11

The root part of Paeonia lactiflora Pall., commonly known as peony, is a commonly used Chinese herb for the treatment of depression-like disorders. Previous studies in our laboratory have showed that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to investigate the mechanism(s) underlying the antidepressant-like action of TGP by measuring neurotrophins including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in non-stressed and chronic unpredictable mild stress (CUMS)-treated rats. TGP (80 or 160 mg/kg/day) was administered by oral gavage to the animals for 5 weeks. The results showed that CUMS caused depression-like behavior in rats, as indicated by the significant decreases in sucrose consumption and locomotor activity (assessed by open-field test). In addition, it was found that BDNF contents in the hippocampus and frontal cortex were significantly decreased in CUMS-treated rats. CUMS treatment also significantly decreased the level of NGF in the frontal cortex of the animals. Daily intragastric administration of TGP (80 or 160 mg/kg/day) during the five weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. Treating non-stressed animals with TGP (160 mg/kg) for 5 weeks also significantly increased BDNF contents in the hippocampus and frontal cortex, and NGF contents in the frontal cortex. The results suggest that the antidepressant-like action of TGP is mediated, at least in part, by increasing the expression of BDNF and NGF in selective brain tissues. Copyright 2010 Elsevier B.V. All rights reserved.

Design of patient-specific focused ultrasound arrays for non-invasive brain therapy with increased trans-skull transmission and steering range

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Hughes, Alec; Hynynen, Kullervo

2017-09-01

The use of a phased array of ultrasound transducer elements to sonicate through the skull has opened the way for new treatments and the delivery of therapeutics beyond the blood-brain barrier. The limited steering range of current clinical devices, particularly at higher frequencies, limits the regions of the brain that are considered treatable by ultrasound. A new array design is introduced that allows for high levels of beam steering and increased transmission throughout the brain. These improvements are achieved using concave transducers normal to the outer-skull surface in a patient-specific configuration to target within the skull, so that the far-field of each beam is within the brain. It is shown that by using pulsed ultrasound waves timed to arrive in-phase at the desired target, sufficient levels of acoustic energy are delivered for blood-brain barrier opening throughout the brain.

Increased cerebral blood flow in MELAS shown by Tc-99m HMPAO brain SPECT

International Nuclear Information System (INIS)

Peng, N.J.; Tsay, D.G.; Liu, R.S.; Li, J.Y.; Kong, K.W.; Kwok, C.G.; Strauss, H.W.

2000-01-01

We report cerebral SPECT studies on two siblings with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Tc-99m HMPAO brain SPECT was performed 8, 19 and 30 days after a stroke-like episode in one case and 10 days after a stroke-like episode, 6 h after a partial seizure and as a follow-up study in the other. Increased blood flow was seen in both these patients with stroke-like episodes due to MELAS. The cause of the increased blood flow is uncertain, but it may be related to the decreased pH created by local increase in lactic acid. (orig.)

Examination of Blood-Brain Barrier (BBB) Integrity In A Mouse Brain Tumor Model

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On, Ngoc; Mitchell, Ryan; Savant, Sanjot D.; Bachmeier, Corbin. J.; Hatch, Grant M.; Miller, Donald W.

2013-01-01

The present study evaluates, both functionally and biochemically, brain tumor-induced alterations in brain capillary endothelial cells. Brain tumors were induced in Balb/c mice via intracranial injection of Lewis Lung carcinoma (3LL) cells into the right hemisphere of the mouse brain using stereotaxic apparatus. Blood-brain barrier (BBB) permeability was assessed at various stages of tumor development, using both radiolabeled tracer permeability and magnetic resonance imaging (MRI) with gadolinium diethylene-triamine-pentaacetate contrast enhancement (Gad-DTPA). The expression of the drug efflux transporter, P-glycoprotein (P-gp), in the BBB at various stages of tumor development was also evaluated by Western blot and immunohistochemistry. Median mouse survival following tumor cell injection was 17 days. The permeability of the BBB to 3H-mannitol was similar in both brain hemispheres at 7 and 10 days post-injection. By day 15, there was a 2-fold increase in 3H-mannitol permeability in the tumor bearing hemispheres compared to the non-tumor hemispheres. Examination of BBB permeability with Gad-DTPA contrast enhanced MRI indicated cerebral vascular permeability changes were confined to the tumor area. The permeability increase observed at the later stages of tumor development correlated with an increase in cerebral vascular volume suggesting angiogenesis within the tumor bearing hemisphere. Furthermore, the Gad-DPTA enhancement observed within the tumor area was significantly less than Gad-DPTA enhancement within the circumventricular organs not protected by the BBB. Expression of P-gp in both the tumor bearing and non-tumor bearing portions of the brain appeared similar at all time points examined. These studies suggest that although BBB integrity is altered within the tumor site at later stages of development, the BBB is still functional and limiting in terms of solute and drug permeability in and around the tumor. PMID:23184143

Reversible brain shrinkage in abstinent alcoholics, measured by MRI

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Schroth, G.; Naegele, T.; Klose, U.; Petersen, D.; Mann, K.

1988-11-01

Magnetic resonance imaging of the intracranial CSF volume was compared before and after 5 weeks of confirmed abstinence in 9 alcohol-dependent patients. All patients showed a highly significant reduction in CSF volume in accordance with reexpansion of the brain after alcohol abstinence. T2 values for white matter, estimated by linear regression from 16 echoes of a CPGM sequence, however, showed no significant increase such as occurs in rehydration. This indicates, that alcohol-induced reversible brain atrophy cannot be attributed to fluctuation of free water in the brain only.

Taurine reverses sodium fluoride-mediated increase in inflammation, caspase-3 activity, and oxidative damage along the brain-pituitary-gonadal axis in male rats.

Science.gov (United States)

Adedara, Isaac A; Olabiyi, Bolanle F; Ojuade, TeminiJesu D; Idris, Umar F; Onibiyo, Esther M; Farombi, Ebenezer O

2017-09-01

Excessive exposure to fluoride is associated with male reproductive dysfunction in humans and animals. Taurine (2-aminoethane sulfonic acid) is a free intracellular β-amino acid with antioxidant, anti-inflammatory, and neuroprotective properties. However, the effect of taurine on fluoride-induced reproductive toxicity has not been reported. The present study investigated the influence of taurine on sodium fluoride (NaF)-induced functional changes along the brain-pituitary-gonadal axis in male rats. NaF was administered singly in drinking water at 15 mg·L -1 alone or orally co-administered by gavage with taurine at 100 and 200 mg·(kg body mass) -1 for 45 consecutive days. Results showed that taurine significantly prevented NaF-induced increase in oxidative stress indices as well as augmented antioxidant enzymes activities and glutathione level in the brain, testes, and epididymis of the treated rats. Moreover, taurine reversed NaF-induced elevation in inflammatory biomarkers and caspase-3 activity as well as histological damage in the brain, testes, and epididymis of the treated rats. The significant reversal of NaF-induced decreases in testosterone level and testicular activities of acid phosphatase, alkaline phosphatase, and lactate dehydrogenase by taurine was accompanied by enhancement of sperm functional characteristics in the treated rats. Taurine may be a possible chemopreventive candidate against reproductive dysfunction resulting from fluoride exposure.

Significance of high-intensity signals on cranial MRI T2 weighted image in diagnosis of age-associated dementia. From a viewpoint of reversibility of brain function

International Nuclear Information System (INIS)

Kishiro, Masaki

1994-01-01

This study was undertaken to determine whether changes of EEG band profile in patients showing high-intensity signal (HIS) on cranial magnetic resonance images (MRI), who had however no vascular lesions on cranial CT, were similar to those in multi-infarct dementia (MID) or senile dementia of Alzheimer type (SDAT) patients and to determine the significance of HIS in the diagnosis of SDAT. Forty-two patients with dementia diagnosed according to DSM-III-R were divided into HIS (n=21), MID (n=13), and SDAT (n=8) based on CT and MRI findings. Multi-infarcted lesions were seen on cranial CT and HIS was seen on cranial MRI in MID patients. There were no abnormal lesions except brain atrophy on cranial CT and MRI in SDAT patients. Appearance rates (%) of the 2-18 c/s frequency bands using computerized quantitative EEG before and after administration of protirelin tartrate (TRH-T) were analyzed in the frontal, central, parietal and occipital areas of the brain. There were no significant differences in appearance rates of EEG frequency bands before administration of TRH-T in HIS, MID, and SDAT patients. A significant decrease in appearance rates of slow waves and a significant increase in appearance rates of α waves were observed after administration of TRH-T in the four areas in MID patients compared with those before administration. No significant differences in appearance rates of EEG frequency bands were observed after administration of TRH-T in the four areas in HIS and SDAT patients compared with those before administration. Changes of the EEG band profile in HIS patients were similar to those in SDAT patients. In the presence of appearance of HSI on cranial MRI T 2 weighted images, the possibility of SDAT patients cannot be excluded. Therefore, SDAT should be diagnosed based on both clinical data and the absence of brain vascular lesions on cranial CT. Also, HIS on MRI T 2 -weighted images is considered to reflect non-vascular lesions. (J.N.P.)

Brain functional connectivity and cognition in mild traumatic brain injury

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Xiong, K.L.; Zhang, Y.L.; Chen, H.; Zhang, J.N.; Zhang, Y.; Qiu, M.G.

2016-01-01

The aim of this study was to analyze brain functional connectivity and its relationship to cognition in patients with mild traumatic brain injury (mTBI). Twenty-five patients with mTBI and 25 healthy control subjects were studied using resting-state functional MRI (rs-fMRI). Amplitudes of low-frequency fluctuations (ALFFs) and functional connectivity (FC) were calculated and correlated with cognition. Compared with the normal control group, the mTBI patients showed a significant decrease in working memory index (WMI) and processing speed index (PSI), as well as significantly decreased ALFFs in the cingulate gyrus, the middle frontal gyrus and superior frontal gyrus. In contrast, the mTBI patients' ALFFs in the left middle occipital gyrus, the left precuneus, and lingual gyrus increased. Additionally, FC significantly decreased in the thalamus, caudate nucleus, and right hippocampus in the mTBI patients. Statistical analysis further showed a significant positive correlation between the ALFF in the cingulate gyrus and the WMI (R 2 = 0.423, P < 0.05) and a significant positive correlation between the FC in the left thalamus and left middle frontal gyrus and the WMI (R 2 = 0.381, P < 0.05). rs-fMRI can reveal the functional state of the brain in patients with mTBI. This finding differed from observations of the normal control group and was significantly associated with clinical cognitive dysfunction. Therefore, rs-fMRI offers an objective imaging modality for treatment planning and prognosis assessment in patients with mTBI. (orig.)

Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men.

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Zoladz, J A; Pilc, A; Majerczak, J; Grandys, M; Zapart-Bukowska, J; Duda, K

2008-12-01

It is believed that brain derived neurotrophic factor (BDNF) plays an important role in neuronal growth, transmission, modulation and plasticity. Single bout of exercise can increase plasma BDNF concentration [BDNF](p) in humans. It was recently reported however, that elevated [BDNF](p) positively correlated with risk factors for metabolic syndrome and type 2 diabetes mellitus in middle age group of subjects. On the other hand it is well established that endurance training decreases the risk of diabetes and development of metabolic syndrome. In the present study we have examined the effect of 5 weeks of moderate intensity endurance training on the basal and the exercise induced changes in [BDNF](p) in humans. Thirteen young, healthy and physically active men (mean +/- S.E: age 22.7 +/- 0.5 yr, body height 180.2 +/- 1.7 cm, body weight 77.0 +/- 2.5 kg, V(O2max) 45.29 +/- 0.93 ml x kg-1 x min(-1)) performed a five week endurance cycling training program, composed mainly of moderate intensity bouts. Before training [BDNF]p at rest have amounted to 10.3 +/- 1.4 pg x ml(-1). No effect of a single maximal incremental cycling up to V(O2max) on its concentration was found (10.9 +/- 2.3 pg x ml(-1), P=0.74). The training resulted in a significant (P=0.01) increase in [BDNF]p at rest to 16.8 +/- 2.1 pg x ml(-1), as well as in significant (P=0.0002) exercise induced increase in the [BDNF](p) (10.9 +/- 2.3 pg x ml(-1) before training vs. 68.4 +/- 16.0 pg x ml(-1) after training). The training induced increase in resting [BDNF](p) was accompanied by a slight decrease in insulin resistance (P=0.25), calculated using the homeostatic model assessment version 2 (HOMA2-IR), amounting to 1.40 +/- 0.13 before and 1.15 +/- 0.13 after the training. Moreover, we have found that the basal [BDNF](p) in athletes (n=16) was significantly higher than in untrained subjects (n=13) (29.5 +/- 9.5 pg x ml(-1) vs. 10.3 +/- 1.4 pg x ml(-1), P=0.013). We have concluded that endurance training of

Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose below 1 mM in patients with severe traumatic brain injury

OpenAIRE

Meierhans, Roman; B?chir, Markus; Ludwig, Silke; Sommerfeld, Jutta; Brandi, Giovanna; Haberth?r, Christoph; Stocker, Reto; Stover, John F

2010-01-01

Introduction The optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism. Methods In twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 ?l/min, collecting samples at 60 minute intervals. Occult metabolic alteratio...

Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose beneath 1 mM in patients with severe traumatic brain injury.

OpenAIRE

Meierhans, R; Bechir, M; Ludwig, S; Sommerfeld, J; Brandi, G; Haberthur, C; Stocker, R; Stover, J F

2010-01-01

ABSTRACT: INTRODUCTION: The optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism. METHODS: In twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 mul/ min, collecting samples at 60 minute intervals. Occult metab...

N-3 fatty acids reduced trans fatty acids retention and increased docosahexaenoic acid levels in the brain.

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Lavandera, Jimena Verónica; Saín, Juliana; Fariña, Ana Clara; Bernal, Claudio Adrián; González, Marcela Aída

2017-09-01

The levels of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are critical for the normal structure and function of the brain. Trans fatty acids (TFA) and the source of the dietary fatty acids (FA) interfere with long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis. The aim of this study was to investigate the effect of TFA supplementation in diets containing different proportions of n-9, n-6, and n-3 FA on the brain FA profile, including the retention of TFA, LC-PUFA levels, and n-6/n-3 PUFA ratios. These parameters were also investigated in the liver, considering that LC-PUFA are mainly bioconverted from their dietary precursors in this tissue and transported by serum to the brain. Also, stearoyl-CoA desaturase-1 (SCD1) and sterol regulatory element-binding protein-1c (SREBP-1c) gene expressions were evaluated. Male CF1 mice were fed (16 weeks) diets containing different oils (olive, corn, and rapeseed) with distinct proportions of n-9, n-6, and n-3 FA (55.2/17.2/0.7, 32.0/51.3/0.9, and 61.1/18.4/8.6), respectively, substituted or not with 0.75% of TFA. FA composition of the brain, liver, and serum was assessed by gas chromatography. TFA were incorporated into, and therefore retained in the brain, liver, and serum. However, the magnitude of retention was dependent on the tissue and type of isomer. In the brain, total TFA retention was lower than 1% in all diets. Dietary n-3 PUFA decreased TFA retention and increased DHA accretion in the brain. The results underscore the importance of the type of dietary FA on the retention of TFA in the brain and also on the changes of the FA profile.

Application of 31P MR spectroscopy to the brain tumors

International Nuclear Information System (INIS)

Ha, Dong Ho; Choi, Sun Seob; Oh, Jong Young; Yoon, Seong Kuk; Kang, Myong Jin; Kim, Ki Uk

2013-01-01

To evaluate the clinical feasibility and obtain useful parameters of 3 1P magnetic resonance spectroscopy (MRS) study for making the differential diagnosis of brain tumors. Twenty-eight patients with brain tumorous lesions (22 cases of brain tumor and 6 cases of abscess) and 11 normal volunteers were included. The patients were classified into the astrocytoma group, lymphoma group, metastasis group and the abscess group. We obtained the intracellular pH and the metabolite ratios of phosphomonoesters/phosophodiesters (PME/PDE), PME/inorganic phosphate (Pi), PDE/Pi, PME/adenosine triphosphate (ATP), PDE/ATP, PME/phosphocreatine (PCr), PDE/PCr, PCr/ATP, PCr/Pi, and ATP/Pi, and evaluated the statistical significances. The brain tumors had a tendency of alkalization (pH = 7.28 ± 0.27, p = 0.090), especially the pH of the lymphoma was significantly increased (pH = 7.45 ± 0.32, p = 0.013). The brain tumor group showed increased PME/PDE ratio compared with that in the normal control group (p 0.012). The ratios of PME/PDE, PDE/Pi, PME/PCr and PDE/PCr showed statistically significant differences between each brain lesion groups (p 1 'P MRS, and the pH, PME/PDE, PDE/Pi, PME/PCr, and PDE/PCr ratios are helpful for differentiating among the different types of brain tumors.

Increased working memory-related brain activity in middle-aged women with cognitive complaints.

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Dumas, Julie A; Kutz, Amanda M; McDonald, Brenna C; Naylor, Magdalena R; Pfaff, Ashley C; Saykin, Andrew J; Newhouse, Paul A

2013-04-01

Individuals who report subjective cognitive complaints but perform normally on neuropsychological tests might be at increased risk for pathological cognitive aging. The current study examined the effects of the presence of subjective cognitive complaints on functional brain activity during a working memory task in a sample of middle-aged postmenopausal women. Twenty-three postmenopausal women aged 50-60 completed a cognitive complaint battery of questionnaires. Using 20% of items endorsed as the threshold, 12 women were categorized as cognitive complainers (CC) and 11 were noncomplainers (NC). All subjects then took part in a functional magnetic resonance imaging scanning session during which they completed a visual-verbal N-back test of working memory. Results showed no difference in working memory performance between CC and NC groups. However, the CC group showed greater activation relative to the NC group in a broad network involved in working memory including the middle frontal gyrus (Brodmann area [BA] 9 and 10), the precuneus (BA 7), and the cingulate gyrus (BA 24 and 32). The CC group recruited additional regions of the working memory network compared with the NC group as the working memory load and difficulty of the task increased. This study showed brain activation differences during working memory performance in a middle-aged group of postmenopausal women with subjective cognitive complaints but without objective cognitive deficit. These findings suggest that subjective cognitive complaints in postmenopausal women might be associated with increased cortical activity during effort-demanding cognitive tasks. Copyright © 2013 Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

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 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

Increased resistin in brain dead organ donors is associated with delayed graft function after kidney transplantation

Science.gov (United States)

2013-01-01

Introduction Resistin increases during several inflammatory diseases and after intracerebral bleeding or head trauma. Resistin activates the endothelium and may initiate an inflammatory response. No data are available on resistin in brain dead donors (DBD) that regularly manifest a pronounced inflammatory state. Methods We analyzed plasma resistin in 63 DBDs and correlated results with donor variables and the postoperative course following kidney transplantation using organs from these donors. Endocan and monocyte chemotactic protein (MCP)-1 were also studied. Twenty-six live kidney donors (LD) and the corresponding kidney transplantations were used as controls. Results DBDs had higher resistin (median/range 30.75 ng/ml, 5.41–173.6) than LD (7.71 ng/ml, 2.41–15.74, p organ retrieval are associated with DGF after kidney transplantation. The resistin increase seems related to the inflammatory state after brain death but not to the cause of death. PMID:24070260

Positron-labeled antioxidant 6-deoxy-6-[{sup 18}F]fluoro-L-ascorbic acid: Increased uptake in transient global ischemic rat brain

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Fumihiko; Shibata, Shigenobu; Watanabe, Shigenori; Masuda, Kouji; Maeda, Minoru

1996-05-01

The in vivo uptake and distribution of 6-deoxy-6-[{sup 18}F]fluoro-L-ascorbic acid ({sup 18}F-DFA) were investigated in rat brains following postischemic reperfusion. Global cerebral ischemia was induced in male Wistar rats for 20 min by occlusion of four major arteries. Two time points were chosen for {sup 18}F-DFA injection to rats subjected to cerebral ischemia, at the start of recirculation and 5 days following recirculation. The rats were then killed at 2 h after tail-vein administration of {sup 18}F-DFA and tissue radioactivity concentration was determined. Increased uptake of radioactivity in particular brain regions, including the cerebral cortex, hypothalamus, and amygdala following injection of {sup 18}F-DFA, compared to the sham-operated control, was observed 5 days after reperfusion. Similar results were also obtained in in vitro experiments using brain slices. Abnormal in vivo accumulation of {sup 45}Ca, a marker of regional postischemic injury, was observed in these brain regions in tissue dissection experiments. Furthermore, metabolite analysis of nonradioactive DFA using {sup 19}F-NMR showed that DFA remained intact in the postischemic reperfusion brain. The present results indicate that {sup 18}F-DFA increasingly accumulates in damaged regions of postischemic reperfusion brain.

Methyl group balance in brain and liver: role of choline on increased S-adenosyl methionine (SAM) demand by chronic arsenic exposure.

Science.gov (United States)

Ríos, Rosalva; Santoyo, Martha E; Cruz, Daniela; Delgado, Juan Manuel; Zarazúa, Sergio; Jiménez-Capdeville, María E

2012-11-30

Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A strategy for increasing the brain uptake of a radioligand in animals: use of a drug that inhibits plasma protein binding

International Nuclear Information System (INIS)

Haradahira, Terushi; Zhang, Ming-Rong; Maeda, Jun; Okauchi, Takashi; Kawabe, Kouichi; Kida, Takayo; Suzuki, Kazutoshi; Suhara, Tetsuya

2000-01-01

A positron-emitter labeled radioligand for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor, [ 11 C]L-703,717, was examined for its ability to penetrate the brain in animals by simultaneous use with drugs having high-affinity separate binding sites on human serum albumin. [ 11 C]L-703,717 has poor blood-brain barrier (BBB) permeability because it binds tightly to plasma proteins. Co-injection of warfarin (50-200 mg/kg), a drug that binds to albumin and resembles L-703,717 in structure, dose-dependently enhanced the penetration by [ 11 C]L-703,717 in mice, resulting in a five-fold increase in the brain radioactivity at 1 min after the injection. Drugs structurally unrelated to L-703,717, salicylate, phenol red, and L-tryptophan, were less effective or ineffective in increasing the uptake of [ 11 C]L-703,717. These results suggest that the simultaneous use of a drug that inhibits the binding of a radioligand to plasma proteins is a useful way to overcome the poor BBB permeability of the radioligand triggered by its tight binding to plasma proteins. In brain distribution studies in rodents, it was found that, after the increase in brain uptake with warfarin, much of the glycine site antagonist accumulates in the cerebellum but its pharmacological specificity did not match the glycine site of NMDA receptors

A Ketone Ester Diet Increases Brain Malonyl-CoA and Uncoupling Proteins 4 and 5 while Decreasing Food Intake in the Normal Wistar Rat*

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Kashiwaya, Yoshihiro; Pawlosky, Robert; Markis, William; King, M. Todd; Bergman, Christian; Srivastava, Shireesh; Murray, Andrew; Clarke, Kieran; Veech, Richard L.

2010-01-01

Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mm and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD+]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain l-glutamate by 15–20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain. PMID:20529850

A ketone ester diet increases brain malonyl-CoA and Uncoupling proteins 4 and 5 while decreasing food intake in the normal Wistar Rat.

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Kashiwaya, Yoshihiro; Pawlosky, Robert; Markis, William; King, M Todd; Bergman, Christian; Srivastava, Shireesh; Murray, Andrew; Clarke, Kieran; Veech, Richard L

2010-08-20

Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mm and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD(+)]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain L-glutamate by 15-20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain.

Selection for increased voluntary wheel-running affects behavior and brain monoamines in mice

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Waters, R.Parrish; Pringle, R.B.; Forster, G.L.; Renner, K.J.; Malisch, J.L.; Garland, T.; Swallow, J.G.

2013-01-01

Selective-breeding of house mice for increased voluntary wheel-running has resulted in multiple physiological and behavioral changes. Characterizing these differences may lead to experimental models that can elucidate factors involved in human diseases and disorders associated with physical inactivity, or potentially treated by physical activity, such as diabetes, obesity, and depression. Herein, we present ethological data for adult males from a line of mice that has been selectively bred for high levels of voluntary wheel-running and from a non-selected control line, housed with or without wheels. Additionally, we present concentrations of central monoamines in limbic, striatal, and midbrain regions. We monitored wheel-running for 8 weeks, and observed home-cage behavior during the last 5 weeks of the study. Mice from the selected line accumulated more revolutions per day than controls due to increased speed and duration of running. Selected mice exhibited more active behaviors than controls, regardless of wheel access, and exhibited less inactivity and grooming than controls. Selective-breeding also influenced the longitudinal patterns of behavior. We found statistically significant differences in monoamine concentrations and associated metabolites in brain regions that influence exercise and motivational state. These results suggest underlying neurochemical differences between selected and control lines that may influence the observed differences in behavior. Our results bolster the argument that selected mice can provide a useful model of human psychological and physiological diseases and disorders. PMID:23352668

Repeated administration of fresh garlic increases memory retention in rats.

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Haider, Saida; Naz, Nosheen; Khaliq, Saima; Perveen, Tahira; Haleem, Darakhshan J

2008-12-01

Garlic (Allium sativum) is regarded as both a food and a medicinal herb. Increasing attention has focused on the biological functions and health benefits of garlic as a potentially major dietary component. Chronic garlic administration has been shown to enhance memory function. Evidence also shows that garlic administration in rats affects brain serotonin (5-hydroxytryptamine [5-HT]) levels. 5-HT, a neurotransmitter involved in a number of physiological functions, is also known to enhance cognitive performance. The present study was designed to investigate the probable neurochemical mechanism responsible for the enhancement of memory following garlic administration. Sixteen adult locally bred male albino Wistar rats were divided into control (n = 8) and test (n = 8) groups. The test group was orally administered 250 mg/kg fresh garlic homogenate (FGH), while control animals received an equal amount of water daily for 21 days. Estimation of plasma free and total tryptophan (TRP) and whole brain TRP, 5-HT, and 5-hydroxyindole acetic acid (5-HIAA) was determined by high-performance liquid chromatography with electrochemical detection. For assessment of memory, a step-through passive avoidance paradigm (electric shock avoidance) was used. The results showed that the levels of plasma free TRP significantly increased (P < .01) and plasma total TRP significantly decreased (P < .01) in garlic-treated rats. Brain TRP, 5-HT, and 5-HIAA levels were also significantly increased following garlic administration. A significant improvement in memory function was exhibited by garlic-treated rats in the passive avoidance test. Increased brain 5-HT levels were associated with improved cognitive performance. The present results, therefore, demonstrate that the memory-enhancing effect of garlic may be associated with increased brain 5-HT metabolism in rats. The results further support the use of garlic as a food supplement for the enhancement of memory.

Changes in brain-behavior relationships following a 3-month pilot cognitive intervention program for adults with traumatic brain injury

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S. Porter

2017-08-01

Full Text Available Facilitating functional recovery following brain injury is a key goal of neurorehabilitation. Direct, objective measures of changes in the brain are critical to understanding how and when meaningful changes occur, however, assessing neuroplasticity using brain based results remains a significant challenge. Little is known about the underlying changes in functional brain networks that correlate with cognitive outcomes in traumatic brain injury (TBI. The purpose of this pilot study was to assess the feasibility of an intensive three month cognitive intervention program in individuals with chronic TBI and to evaluate the effects of this intervention on brain-behavioral relationships. We used tools from graph theory to evaluate changes in global and local brain network features prior to and following cognitive intervention. Network metrics were calculated from resting state electroencephalographic (EEG recordings from 10 adult participants with mild to severe brain injury and 11 age and gender matched healthy controls. Local graph metrics showed hyper-connectivity in the right inferior frontal gyrus and hypo-connectivity in the left inferior frontal gyrus in the TBI group at baseline in comparison with the control group. Following the intervention, there was a statistically significant increase in the composite cognitive score in the TBI participants and a statistically significant decrease in functional connectivity in the right inferior frontal gyrus. In addition, there was evidence of changes in the brain-behavior relationships following intervention. The results from this pilot study provide preliminary evidence for functional network reorganization that parallels cognitive improvements after cognitive rehabilitation in individuals with chronic TBI.

Changes in brain-behavior relationships following a 3-month pilot cognitive intervention program for adults with traumatic brain injury.

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Porter, S; Torres, I J; Panenka, W; Rajwani, Z; Fawcett, D; Hyder, A; Virji-Babul, N

2017-08-01

Facilitating functional recovery following brain injury is a key goal of neurorehabilitation. Direct, objective measures of changes in the brain are critical to understanding how and when meaningful changes occur, however, assessing neuroplasticity using brain based results remains a significant challenge. Little is known about the underlying changes in functional brain networks that correlate with cognitive outcomes in traumatic brain injury (TBI). The purpose of this pilot study was to assess the feasibility of an intensive three month cognitive intervention program in individuals with chronic TBI and to evaluate the effects of this intervention on brain-behavioral relationships. We used tools from graph theory to evaluate changes in global and local brain network features prior to and following cognitive intervention. Network metrics were calculated from resting state electroencephalographic (EEG) recordings from 10 adult participants with mild to severe brain injury and 11 age and gender matched healthy controls. Local graph metrics showed hyper-connectivity in the right inferior frontal gyrus and hypo-connectivity in the left inferior frontal gyrus in the TBI group at baseline in comparison with the control group. Following the intervention, there was a statistically significant increase in the composite cognitive score in the TBI participants and a statistically significant decrease in functional connectivity in the right inferior frontal gyrus. In addition, there was evidence of changes in the brain-behavior relationships following intervention. The results from this pilot study provide preliminary evidence for functional network reorganization that parallels cognitive improvements after cognitive rehabilitation in individuals with chronic TBI.

Sustained Treatment with Insulin Detemir in Mice Alters Brain Activity and Locomotion.

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Tina Sartorius

Full Text Available Recent studies have identified unique brain effects of insulin detemir (Levemir®. Due to its pharmacologic properties, insulin detemir may reach higher concentrations in the brain than regular insulin. This might explain the observed increased brain stimulation after acute insulin detemir application but it remained unclear whether chronic insulin detemir treatment causes alterations in brain activity as a consequence of overstimulation.In mice, we examined insulin detemir's prolonged brain exposure by continuous subcutaneous (s.c. application using either micro-osmotic pumps or daily s.c. injections and performed continuous radiotelemetric electrocorticography and locomotion recordings.Acute intracerebroventricular injection of insulin detemir activated cortical and locomotor activity significantly more than regular insulin in equimolar doses (0.94 and 5.63 mU in total, suggesting an enhanced acute impact on brain networks. However, given continuously s.c., insulin detemir significantly reduced cortical activity (theta: 21.3±6.1% vs. 73.0±8.1%, P<0.001 and failed to maintain locomotion, while regular insulin resulted in an increase of both parameters.The data suggest that permanently-increased insulin detemir levels in the brain convert its hyperstimulatory effects and finally mediate impairments in brain activity and locomotion. This observation might be considered when human studies with insulin detemir are designed to target the brain in order to optimize treatment regimens.

Speaker gaze increases information coupling between infant and adult brains.

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Leong, Victoria; Byrne, Elizabeth; Clackson, Kaili; Georgieva, Stanimira; Lam, Sarah; Wass, Sam

2017-12-12

When infants and adults communicate, they exchange social signals of availability and communicative intention such as eye gaze. Previous research indicates that when communication is successful, close temporal dependencies arise between adult speakers' and listeners' neural activity. However, it is not known whether similar neural contingencies exist within adult-infant dyads. Here, we used dual-electroencephalography to assess whether direct gaze increases neural coupling between adults and infants during screen-based and live interactions. In experiment 1 ( n = 17), infants viewed videos of an adult who was singing nursery rhymes with ( i ) direct gaze (looking forward), ( ii ) indirect gaze (head and eyes averted by 20°), or ( iii ) direct-oblique gaze (head averted but eyes orientated forward). In experiment 2 ( n = 19), infants viewed the same adult in a live context, singing with direct or indirect gaze. Gaze-related changes in adult-infant neural network connectivity were measured using partial directed coherence. Across both experiments, the adult had a significant (Granger) causal influence on infants' neural activity, which was stronger during direct and direct-oblique gaze relative to indirect gaze. During live interactions, infants also influenced the adult more during direct than indirect gaze. Further, infants vocalized more frequently during live direct gaze, and individual infants who vocalized longer also elicited stronger synchronization from the adult. These results demonstrate that direct gaze strengthens bidirectional adult-infant neural connectivity during communication. Thus, ostensive social signals could act to bring brains into mutual temporal alignment, creating a joint-networked state that is structured to facilitate information transfer during early communication and learning. Copyright © 2017 the Author(s). Published by PNAS.

Increased 5S rRNA oxidation in Alzheimer's disease.

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Ding, Qunxing; Zhu, Haiyan; Zhang, Bing; Soriano, Augusto; Burns, Roxanne; Markesbery, William R

2012-01-01

It is widely accepted that oxidative stress is involved in neurodegenerative disorders such as Alzheimer's disease (AD). Ribosomal RNA (rRNA) is one of the most abundant molecules in most cells and is affected by oxidative stress in the human brain. Previous data have indicated that total rRNA levels were decreased in the brains of subjects with AD and mild cognitive impairment concomitant with an increase in rRNA oxidation. In addition, level of 5S rRNA, one of the essential components of the ribosome complex, was significantly lower in the inferior parietal lobule (IP) brain area of subjects with AD compared with control subjects. To further evaluate the alteration of 5S rRNA in neurodegenerative human brains, multiple brain regions from both AD and age-matched control subjects were used in this study, including IP, superior and middle temporal gyro, temporal pole, and cerebellum. Different molecular pools including 5S rRNA integrated into ribosome complexes, free 5S rRNA, cytoplasmic 5S rRNA, and nuclear 5S rRNA were studied. Free 5S rRNA levels were significantly decreased in the temporal pole region of AD subjects and the oxidation of ribosome-integrated and free 5S rRNA was significantly increased in multiple brain regions in AD subjects compared with controls. Moreover, a greater amount of oxidized 5S rRNA was detected in the cytoplasm and nucleus of AD subjects compared with controls. These results suggest that the increased oxidation of 5S rRNA, especially the oxidation of free 5S rRNA, may be involved in the neurodegeneration observed in AD.

Studies on the effects of aspartame on memory and oxidative stress in brain of mice.

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Abdel-Salam, O M E; Salem, N A; El-Shamarka, M E S; Hussein, J S; Ahmed, N A S; El-Nagar, M E S

2012-12-01

The dipeptide aspartame (N-L-alpha-aspartyl-Lphenylalanine, 1-methyl ester; alpha-APM) is one of the most widely used artificial sweeteners. The present study aimed to investigate the effect of repeated administration of aspartame in the working memory version of Morris water maze test, on oxidative stress and brain monoamines in brain of mice. Aspartame (0.625, 1.875 or 5.625 mg/kg) was administered once daily subcutaneously for 2 weeks and mice were examined four times a week for their ability to locate a submerged plate. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide levels (the concentrations of nitrite/nitrate) and glucose were determined in brain. Only at the highest dose of 5.625 mg/kg, did aspartame significantly impaired water maze performance. The mean time taken to find the escape platform (latency) over 2 weeks was significantly delayed by aspartame 5.625 mg/kg, compared with the saline-treated control group. Significant differences occurred only on the first trial to find the escape platform. Significant increase in brain MDA by 16.5% and nitric oxide by 16.2% and a decrease in GSH by 25.1% and glucose by 22.5% occurred after treatment with aspartame at 1.875 mg/kg. Aspartame administered at 5.625 mg/kg significantly increased brain MDA by 43.8%, nitric oxide by 18.6% and decreased GSH by 32.7% and glucose by 25.8%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline and dopamine. These findings suggest impaired memory performance and increased brain oxidative stress by repeated aspartame administration. The impaired memory performance is likely to involve increased oxidative stress as well as decreased brain glucose availability.

Strategies to increase the activity of microglia as efficient protectors of the brain against infections

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Roland eNau

2014-05-01

Full Text Available In healthy individuals, infections of the CNS are comparatively rare. Based on the ability of microglial cells to phagocytose and kill pathogens and on clinical findings in immunocompromized patients with CNS infections, we hypothesize that an intact microglial function is crucial to protect the brain from infections. Phagocytosis of pathogens by microglial cells can be stimulated by agonists of receptors of the innate immune system. Enhancing this pathway to increase the resistance of the brain to infections entails the risk of inducing collateral damage to the nervous tissue. The diversity of microglial cells opens avenue to selectively stimulate sub-populations responsible for the defence against pathogens without stimulating sub-populations which are responsible for collateral damage to the nervous tissue. Palmitoylethanolamide (PEA, an endogenous lipid, increased phagocytosis of bacteria by microglial cells in vitro without a measurable proinflammatory effect. It was tested clinically apparently without severe side effects. Glatiramer acetate increased phagocytosis of latex beads by microglia and monocytes, and dimethyl fumarate enhanced elimination of human immunodeficiency virus from infected macrophages without inducing a release of proinflammatory compounds. Therefore, the discovery of compounds which stimulate the elimination of pathogens without collateral damage of neuronal structures appears an achievable goal. PEA and, with limitations, glatiramer acetate and dimethyl fumarate appear promising candidates.

Reduction in cardiolipin decreases mitochondrial spare respiratory capacity and increases glucose transport into and across human brain cerebral microvascular endothelial cells.

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Nguyen, Hieu M; Mejia, Edgard M; Chang, Wenguang; Wang, Ying; Watson, Emily; On, Ngoc; Miller, Donald W; Hatch, Grant M

2016-10-01

Microvessel endothelial cells form part of the blood-brain barrier, a restrictively permeable interface that allows transport of only specific compounds into the brain. Cardiolipin is a mitochondrial phospholipid required for function of the electron transport chain and ATP generation. We examined the role of cardiolipin in maintaining mitochondrial function necessary to support barrier properties of brain microvessel endothelial cells. Knockdown of the terminal enzyme of cardiolipin synthesis, cardiolipin synthase, in hCMEC/D3 cells resulted in decreased cellular cardiolipin levels compared to controls. The reduction in cardiolipin resulted in decreased mitochondrial spare respiratory capacity, increased pyruvate kinase activity, and increased 2-deoxy-[(3) H]glucose uptake and glucose transporter-1 expression and localization to membranes in hCMEC/D3 cells compared to controls. The mechanism for the increase in glucose uptake was an increase in adenosine-5'-monophosphate kinase and protein kinase B activity and decreased glycogen synthase kinase 3 beta activity. Knockdown of cardiolipin synthase did not affect permeability of fluorescent dextran across confluent hCMEC/D3 monolayers grown on Transwell(®) inserts. In contrast, knockdown of cardiolipin synthase resulted in an increase in 2-deoxy-[(3) H]glucose transport across these monolayers compared to controls. The data indicate that in hCMEC/D3 cells, spare respiratory capacity is dependent on cardiolipin. In addition, reduction in cardiolipin in these cells alters their cellular energy status and this results in increased glucose transport into and across hCMEC/D3 monolayers. Microvessel endothelial cells form part of the blood-brain barrier, a restrictively permeable interface that allows transport of only specific compounds into the brain. In human adult brain endothelial cell hCMEC/D3 monolayers cultured on Transwell(®) plates, knockdown of cardiolipin synthase results in decrease in mitochondrial

Methamphetamine transiently increases the blood-brain barrier permeability in the hippocampus: role of tight junction proteins and matrix metalloproteinase-9.

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Martins, Tânia; Baptista, Sofia; Gonçalves, Joana; Leal, Ermelindo; Milhazes, Nuno; Borges, Fernanda; Ribeiro, Carlos F; Quintela, Oscar; Lendoiro, Elena; López-Rivadulla, Manuel; Ambrósio, António F; Silva, Ana P

2011-09-09

Methamphetamine (METH) is a powerful stimulant drug of abuse that has steadily gained popularity worldwide. It is known that METH is highly neurotoxic and causes irreversible damage of brain cells leading to neurological and psychiatric abnormalities. Recent studies suggested that METH-induced neurotoxicity might also result from its ability to compromise blood-brain barrier (BBB) function. Due to the crucial role of BBB in the maintenance of brain homeostasis and protection against toxic molecules and pathogenic organisms, its dysfunction could have severe consequences. In this study, we investigated the effect of an acute high dose of METH (30mg/kg) on BBB permeability after different time points and in different brain regions. For that, young adult mice were sacrificed 1h, 24h or 72h post-METH administration. METH increased BBB permeability, but this effect was detected only at 24h after administration, being therefore a transitory effect. Interestingly, we also found that the hippocampus was the most susceptible brain region to METH, comparing to frontal cortex and striatum. Moreover, in an attempt to identify the key players in METH-induced BBB dysfunction we further investigated potential alterations in tight junction (TJ) proteins and matrix metalloproteinase-9 (MMP-9). METH was able to decrease the protein levels of zonula occludens (ZO)-1, claudin-5 and occludin in the hippocampus 24h post-injection, and increased the activity and immunoreactivity of MMP-9. The pre-treatment with BB-94 (30mg/kg), a matrix metalloproteinase inhibitor, prevented the METH-induced increase in MMP-9 immunoreactivity in the hippocampus. Overall, the present data demonstrate that METH transiently increases the BBB permeability in the hippocampus, which can be explained by alterations on TJ proteins and MMP-9. Copyright © 2011 Elsevier B.V. All rights reserved.

Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states.

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Sachiko Chikahisa

Full Text Available Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS. Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing especially on the histaminergic system, using mast cell deficient (W/W(v mice. No significant difference was found in the basal amount of sleep/wake between W/W(v mice and their wild-type littermates (WT, although W/W(v mice showed increased EEG delta power and attenuated rebound response after sleep deprivation. Intracerebroventricular injection of compound 48/80, a histamine releaser from mast cells, significantly increased histamine levels in the ventricular region and enhanced wakefulness in WT mice, while it had no effect in W/W(v mice. Injection of H1 antagonists (triprolidine and mepyramine significantly increased the amounts of slow-wave sleep in WT mice, but not in W/W(v mice. Most strikingly, the food-seeking behavior observed in WT mice during food deprivation was completely abolished in W/W(v mice. W/W(v mice also exhibited higher anxiety and depression levels compared to WT mice. Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior.

Larger ATV engine size correlates with an increased rate of traumatic brain injury.

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Butts, C Caleb; Rostas, Jack W; Lee, Y L; Gonzalez, Richard P; Brevard, Sidney B; Frotan, M Amin; Ahmed, Naveed; Simmons, Jon D

2015-04-01

Since the introduction of all-terrain vehicles (ATV) to the United States in 1971, injuries and mortalities related to their use have increased significantly. Furthermore, these vehicles have become larger and more powerful. As there are no helmet requirements or limitations on engine-size in the State of Alabama, we hypothesised that larger engine size would correlate with an increased incidence of traumatic brain injury (TBI) in patients following an ATV crash. Patient and ATV data were prospectively collected on all ATV crashes presenting to a level one trauma centre from September 2010 to May 2013. Collected data included: demographics, age of driver, ATV engine size, presence of helmet, injuries, and outcomes. The data were grouped according to the ATV engine size in cubic centimetres (cc). For the purposes of this study, TBI was defined as any type of intracranial haemorrhage on the initial computed tomography scan. There were 61 patients identified during the study period. Two patients (3%) were wearing a helmet at the time of injury. Patients on an ATV with an engine size of 350 cc or greater had higher Injury Severity Scores (13.9 vs. 7.5, p ≤ 0.05) and an increased incidence of TBI (26% vs. 0%, p ≤ 0.05) when compared to patients on ATV's with an engine size less than 350 cc. Patients on an ATV with an engine size of 350 cc or greater were more likely to have a TBI. The use of a helmet was rarely present in this cohort. Legislative efforts to implement rider protection laws for ATVs are warranted. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of manganese on neonatal rat: manganese concentration and enzymatic alterations in brain

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Seth, P K; Husain, R; Mushtaq, M; Chandra, S V

1977-01-01

Suckling rats were exposed for 15 and 30 days to manganese through the milk of nursing dams receiving 15 mg MnCl/sub 2/.4H/sub 2/O/kg/day orally and after which the neurological manifestations of metal poisoning were studied. No significant differences in the growth rate, developmental landmarks and walking movements were observed between the control and manganese-exposed pups. The metal concentration was significantly increased in the brain of manganese-fed pups at 15 days and exhibited a further three-fold increase over the control, at 30 days. The accumulation of the metal in the brain of manganese-exposed nursing dams was comparatively much less. A significant decrease in succinic dehydrogenase, adenosine triphosphatase, adenosine deaminase, acetylcholine esterase and an increase in monoamine oxidase activity was observed in the brain of experimental pups and dams. The results suggest that the developing brain may also be susceptible to manganese.

Sixteen-Day Bedrest Significantly Increases Plasma Colloid Osmotic Pressure

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Hargens, Alan R.; Hsieh, S. T.; Murthy, G.; Ballard, R. E.; Convertino, V. A.; Wade, Charles E. (Technical Monitor)

1994-01-01

Upon exposure to microgravity, astronauts lose up to 10% of their total plasma volume, which may contribute to orthostatic intolerance after space flight. Because plasma colloid osmotic pressure (COP) is a primary factor maintaining plasma volume, our objective was to measure time course changes in COP during microgravity simulated by 6 deg. head-down tilt (HDT). Seven healthy male subjects (30-55 years of age) were placed in HDT for 16 days. For the purpose of another study, three of the seven subjects were chosen to exercise on a cycle ergometer on day 16. Blood samples were drawn immediately before bedrest on day 14 of bedrest, 18-24 hours following exercise while all subjects were still in HDT and 1 hour following bedrest termination. Plasma COP was measured in all 20 microliter EDTA-treated samples using an osmometer fitted with a PM 30 membrane. Data were analyzed with paired and unpaired t-tests. Plasma COP on day 14 of bedrest (29.9 +/- 0.69 mmHg) was significantly higher (p less than 0.005) than the control, pre-bedrest value (23.1 +/- 0.76 mmHg). At one hour of upright recovery after HDT, plasma COP remained significantly elevated (exercise: 26.9 +/- 0.87 mmHg; no exercise: 26.3 +/- 0.85 mmHg). Additionally, exercise had no significant effect on plasma COP 18-24 hours following exercise (exercise: 27.8 +/- 1.09 mmHg; no exercise: 27.1 +/- 0.78 mmHg). Our results demonstrate that plasma COP increases significantly with microgravity simulated by HDT. However, preliminary results indicate exercise during HDT does not significantly affect plasma COP.

Estimating brain age using high-resolution pattern recognition: Younger brains in long-term meditation practitioners.

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Luders, Eileen; Cherbuin, Nicolas; Gaser, Christian

2016-07-01

Normal aging is known to be accompanied by loss of brain substance. The present study was designed to examine whether the practice of meditation is associated with a reduced brain age. Specific focus was directed at age fifty and beyond, as mid-life is a time when aging processes are known to become more prominent. We applied a recently developed machine learning algorithm trained to identify anatomical correlates of age in the brain translating those into one single score: the BrainAGE index (in years). Using this validated approach based on high-dimensional pattern recognition, we re-analyzed a large sample of 50 long-term meditators and 50 control subjects estimating and comparing their brain ages. We observed that, at age fifty, brains of meditators were estimated to be 7.5years younger than those of controls. In addition, we examined if the brain age estimates change with increasing age. While brain age estimates varied only little in controls, significant changes were detected in meditators: for every additional year over fifty, meditators' brains were estimated to be an additional 1month and 22days younger than their chronological age. Altogether, these findings seem to suggest that meditation is beneficial for brain preservation, effectively protecting against age-related atrophy with a consistently slower rate of brain aging throughout life. Copyright © 2016 Elsevier Inc. All rights reserved.

Significance of high-intensity signals on cranial MRI T{sub 2} weighted image in diagnosis of age-associated dementia. From a viewpoint of reversibility of brain function

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Kishiro, Masaki [St. Marianna Univ., Kawasaki, Kanagawa (Japan). School of Medicine

1994-08-01

This study was undertaken to determine whether changes of EEG band profile in patients showing high-intensity signal (HIS) on cranial magnetic resonance images (MRI), who had however no vascular lesions on cranial CT, were similar to those in multi-infarct dementia (MID) or senile dementia of Alzheimer type (SDAT) patients and to determine the significance of HIS in the diagnosis of SDAT. Forty-two patients with dementia diagnosed according to DSM-III-R were divided into HIS (n=21), MID (n=13), and SDAT (n=8) based on CT and MRI findings. Multi-infarcted lesions were seen on cranial CT and HIS was seen on cranial MRI in MID patients. There were no abnormal lesions except brain atrophy on cranial CT and MRI in SDAT patients. Appearance rates (%) of the 2-18 c/s frequency bands using computerized quantitative EEG before and after administration of protirelin tartrate (TRH-T) were analyzed in the frontal, central, parietal and occipital areas of the brain. There were no significant differences in appearance rates of EEG frequency bands before administration of TRH-T in HIS, MID, and SDAT patients. A significant decrease in appearance rates of slow waves and a significant increase in appearance rates of {alpha} waves were observed after administration of TRH-T in the four areas in MID patients compared with those before administration. No significant differences in appearance rates of EEG frequency bands were observed after administration of TRH-T in the four areas in HIS and SDAT patients compared with those before administration. Changes of the EEG band profile in HIS patients were similar to those in SDAT patients. In the presence of appearance of HSI on cranial MRI T{sub 2} weighted images, the possibility of SDAT patients cannot be excluded. Therefore, SDAT should be diagnosed based on both clinical data and the absence of brain vascular lesions on cranial CT. Also, HIS on MRI T{sub 2}-weighted images is considered to reflect non-vascular lesions. (J.N.P.).

Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucose Metabolism

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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 < .05 (corrected for multiple comparisons) were considered significant. Main Outcome Measure Brain glucose metabolism computed as absolute metabolism (µmol/100 g per minute) and as normalized metabolism (region/whole brain). Results Whole-brain metabolism did not differ between on and off conditions. In contrast, metabolism in the region closest to the antenna (orbitofrontal cortex and temporal pole) was significantly higher for on than off conditions (35.7 vs 33.3 µmol/100 g per minute; mean difference, 2.4 [95% confidence interval, 0.67–4.2]; P = .004). The increases were significantly correlated with the estimated electromagnetic field amplitudes both for absolute metabolism (R = 0.95, P < .001) and normalized metabolism (R = 0.89; P < .001

Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucos Metabolism

International Nuclear Information System (INIS)

Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Vaska, P.; Fowler, J.S.; Telang, F.; Alexoff, D.; Logan, J.; Wong, C.

2011-01-01

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. To evaluate if acute cell phone exposure affects brain glucose metabolism, a marker of brain activity. 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 ( 18 F)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 cm 3 ) and P < .05 (corrected for multiple comparisons) were considered significant. Brain glucose metabolism computed as absolute metabolism ((micro)mol/100 g per minute) and as normalized metabolism (region/whole brain). Whole-brain metabolism did not differ between on and off conditions. In contrast, metabolism in the region closest to the antenna (orbitofrontal cortex and temporal pole) was significantly higher for on than off conditions (35.7 vs 33.3 (micro)mol/100 g per minute; mean difference, 2.4 (95% confidence interval, 0.67-4.2); P = .004). The increases were significantly correlated with the estimated electromagnetic field amplitudes both for absolute metabolism (R = 0.95, P < .001) and normalized metabolism (R = 0.89; P < .001). In healthy participants and compared with no exposure, 50-minute cell phone

Protection of the blood-brain barrier by hypercapnia during acute hypertension

International Nuclear Information System (INIS)

Baumbach, G.L.; Mayhan, W.G.; Heistad, D.D.

1986-01-01

The purpose of this study was to examine effects of hypercapnia on susceptibility of the blood-brain barrier to disruption during acute hypertension. Two methods were used to test the hypothesis that cerebral vasodilation during hypercapnia increases disruption of the blood-brain barrier. First, permeability of the blood-brain barrier was measured in anesthetized cats with 125 I-labeled serum albumin. Severe hypertension markedly increased permeability of the blood-brain barrier during normocapnia, but not during hypercapnia. The protective effect of hypercapnia was not dependent on sympathetic nerves. Second, in anesthetized rats, permeability of the barrier was quantitated by clearance of fluorescent dextran. Disruption of the blood-brain barrier during hypertension was decreased by hypercapnia. Because disruption of the blood-brain barrier occurred primarily in pial venules, the authors also measured pial venular diameter and pressure. Acute hypertension increased pial venular pressure and diameter in normocapnic rats. Hypercapnia alone increased pial venular pressure and pial venular diameter, and acute hypertension during hypercapnia further increased venular pressure. The magnitude of increase in pial venular pressure during acute hypertension was significantly less in hypercapnic than in normocapnic rats. They conclude that hypercapnia protects the blood-brain barrier. Possible mechanisms of this effect include attenuation of the incremental increase in pial venular pressure by hypercapnia or a direct effect on the blood-brain barrier not related to venous pressure

Increased expression of vascular endothelial growth factor attenuates contusion necrosis without influencing contusion edema after traumatic brain injury in rats.

Science.gov (United States)

Tado, Masahiro; Mori, Tatsuro; Fukushima, Masamichi; Oshima, Hideki; Maeda, Takeshi; Yoshino, Atsuo; Aizawa, Shin; Katayama, Yoichi

2014-04-01

To clarify the role of vascular endothelial growth factor (VEGF) in the formation of contusion edema and necrosis after traumatic brain injury, we examined the time course of changes in the VEGF expression (enzyme-linked immunosorbent assay), cerebrovascular permeability (extravasation of Evans blue), and water content (dry-wet weight method) of the contused brain tissue in a cortical impact injury model using rats. In addition, we tested the effects of administration of bevacizumab (VEGF monoclonal antibody) on changes in the cerebrovascular permeability and water content of the contused brain tissue, as well as the neurological deficits (rota rod test) and volume of contusion necrosis. Increased VEGF expression was maximal at 72 h after injury (pnecrosis at 21 days (pnecrosis. This is probably because of an increased angiogenesis and improved microcirculation in the areas surrounding the core of contusion.

[Patterns of brain ageing].

Science.gov (United States)

Fernández Viadero, Carlos; Verduga Vélez, Rosario; Crespo Santiago, Dámaso

2017-06-01

Neuroplasticity lends the brain a strong ability to adapt to changes in the environment that occur during ageing. Animal models have shown alterations in neurotransmission and imbalances in the expression of neural growth factor. Changes at the morphometric level are not constant. Volume loss is related to alterations in neuroplasticity and involvement of the cerebral neuropil. Although there are no conclusive data, physical exercise improves the molecular, biological, functional and behavioural-cognitive changes associated with brain ageing. The aged human brain has been described as showing weight and volume loss and increased ventricular size. However, neuroimaging shows significant variation and many healthy elderly individuals show no significant macroscopic changes. In most brain regions, the number of neurons remains stable throughout life. Neuroplasticity does not disappear with ageing, and changes in dendritic arborization and the density of spines and synapses are more closely related to brain activity than to age. At the molecular level, although the presence of altered Tau and β-amyloid proteins is used as a biomarker of neurodegenerative disease, postmortem studies show that these abnormal proteins are common in the brains of elderly people without dementia. Finally, due to the relationship between neurodegenerative diseases and metabolic alterations, this article analyses the influence of insulin-like growth factor and ageing, both in animal models and in humans, and the possible neuroprotective effect of insulin. Copyright © 2017 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of operating microscope light on brain temperature during craniotomy.

Science.gov (United States)

Gayatri, Parthasarathi; Menon, Girish G; Suneel, Puthuvassery R

2013-07-01

Operating microscopes used during neurosurgery are fitted with xenon light. Burn injuries have been reported because of xenon microscope lighting as the intensity of xenon light is 300 W. We designed this study to find out if the light of operating microscope causes an increase in temperature of the brain tissue, which is exposed underneath. Twenty-one adult patients scheduled for elective craniotomies were enrolled. Distal esophageal temperature (T Eso), brain temperature under the microscope light (T Brain), and brain temperature under dura mater (T Dura) were measured continuously at 15-minute intervals during microscope use. The irrigation fluid temperature, room temperature, intensity of the microscope light, and the distance of the microscope from the brain surface were kept constant. The average age of the patients was 44±15 years (18 males and 3 females). The mean duration of microscope use was 140±39 minutes. There were no significant changes in T Brain and T Dura and T Eso over time. T Dura was significantly lower than T Brain both at time 0 and 60 minutes but not at 90 minutes. T Brain was significantly lower than T Eso both at time 0 and 60 minutes but not at 90 minutes. The T Dura remained significantly lower than T Eso at 0, 60, and 90 minutes. Our study shows that there is no significant rise in brain temperature under xenon microscope light up to 120 minutes duration, at intensity of 60% to 70%, from a distance of 20 to 25 cm from the brain surface.

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

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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.

Deficiency of vasodilator-stimulated phosphoprotein (VASP increases blood-brain-barrier damage and edema formation after ischemic stroke in mice.

Directory of Open Access Journals (Sweden)

Peter Kraft

2010-12-01

Full Text Available Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification.Focal cerebral ischemia was induced in Vasp(-/- mice and wild-type (WT littermates by transient middle cerebral artery occlusion (tMCAO. Evan's Blue tracer was applied to visualize the extent of blood-brain-barrier (BBB damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p0.05 towards worse neurological outcomes.Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage.

Dietary resveratrol administration increases MnSOD expression and activity in mouse brain

International Nuclear Information System (INIS)

Robb, Ellen L.; Winkelmolen, Lieke; Visanji, Naomi; Brotchie, Jonathan; Stuart, Jeffrey A.

2008-01-01

trans-Resveratrol (3,4',5-trihydroxystilbene; RES) is of interest for its reported protective effects in a variety of pathologies, including neurodegeneration. Many of these protective properties have been attributed to the ability of RES to reduce oxidative stress. In vitro studies have shown an increase in antioxidant enzyme activities following exposure to RES, including upregulation of mitochondrial superoxide dismutase, an enzyme that is capable of reducing both oxidative stress and cell death. We sought to determine if a similar increase in endogenous antioxidant enzymes is observed with RES treatment in vivo. Three separate modes of RES delivery were utilized; in a standard diet, a high fat diet and through a subcutaneous osmotic minipump. RES given in a high fat diet proved to be effective in elevating antioxidant capacity in brain resulting in an increase in both MnSOD protein level (140%) and activity (75%). The increase in MnSOD was not due to a substantial proliferation of mitochondria, as RES treatment induced a 10% increase in mitochondrial abundance (Citrate Synthase activity). The potential neuroprotective properties of MnSOD have been well established, and we demonstrate that a dietary delivery of RES is able to increase the expression and activity of this enzyme in vivo

A strategy for increasing the brain uptake of a radioligand in animals: use of a drug that inhibits plasma protein binding

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Haradahira, Terushi E-mail: terushi@nirs.go.jp; Zhang, Ming-Rong; Maeda, Jun; Okauchi, Takashi; Kawabe, Kouichi; Kida, Takayo; Suzuki, Kazutoshi; Suhara, Tetsuya

2000-05-01

A positron-emitter labeled radioligand for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor, [{sup 11}C]L-703,717, was examined for its ability to penetrate the brain in animals by simultaneous use with drugs having high-affinity separate binding sites on human serum albumin. [{sup 11}C]L-703,717 has poor blood-brain barrier (BBB) permeability because it binds tightly to plasma proteins. Co-injection of warfarin (50-200 mg/kg), a drug that binds to albumin and resembles L-703,717 in structure, dose-dependently enhanced the penetration by [{sup 11}C]L-703,717 in mice, resulting in a five-fold increase in the brain radioactivity at 1 min after the injection. Drugs structurally unrelated to L-703,717, salicylate, phenol red, and L-tryptophan, were less effective or ineffective in increasing the uptake of [{sup 11}C]L-703,717. These results suggest that the simultaneous use of a drug that inhibits the binding of a radioligand to plasma proteins is a useful way to overcome the poor BBB permeability of the radioligand triggered by its tight binding to plasma proteins. In brain distribution studies in rodents, it was found that, after the increase in brain uptake with warfarin, much of the glycine site antagonist accumulates in the cerebellum but its pharmacological specificity did not match the glycine site of NMDA receptors.

Induction by mercury compounds of brain metallothionein in rats: Hg{sup 0} exposure induces long-lived brain metallothionein

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Yasutake, Akira; Nakano, Atsuhiro [Biochemistry Section, National Institute for Minamata Disease, Kumamoto (Japan); Hirayama, Kimiko [Kumamoto University, College of Medical Science (Japan)

1998-03-01

Metallothionein (MT) is one of the stress proteins which can easily be induced by various kind of heavy metals. However, MT in the brain is difficult to induce because of blood-brain barrier impermeability to most heavy metals. In this paper, we have attempted to induce brain MT in rats by exposure to methylmercury (MeHg) or metallic mercury vapor, both of which are known to penetrate the blood-brain barrier and cause neurological damage. Rats treated with MeHg (40 {mu}mol/kg per day x 5 days, p.o.) showed brain Hg levels as high as 18 {mu}g/g with slight neurological signs 10 days after final administration, but brain MT levels remained unchanged. However, rats exposed to Hg vapor for 7 days showed 7-8 {mu}g Hg/g brain tissue 24 h after cessation of exposure. At that time brain MT levels were about twice the control levels. Although brain Hg levels fell gradually with a half-life of 26 days, MT levels induced by Hg exposure remained unchanged for >2 weeks. Gel fractionation revealed that most Hg was in the brain cytosol fraction and thus bound to MT. Hybridization analysis showed that, despite a significant increase in MT-I and -II mRNA in brain, MT-III mRNA was less affected. Although significant Hg accumulation and MT induction were observed also in kidney and liver of Hg vapor-exposed rats, these decreased more quickly than in brain. The long-lived MT in brain might at least partly be accounted for by longer half-life of Hg accumulated there. The present results showed that exposure to Hg vapor might be a suitable procedure to provide an in vivo model with enhanced brain MT. (orig.) With 4 figs., 1 tab., 27 refs.

Opioid Abuse After Traumatic Brain Injury: Evaluation Using Rodet Models

Science.gov (United States)

2014-07-01

pressing behavior was less likely to occur in brain-injured subjects following both exposure to oxycodone-associated cues as well as priming with a...pain medications. There is significant overlap in anatomical brain regions involved in reward pathways associated with addiction and the brain regions...commonly damaged in TBI which suggests that TBI could alter the reward circuitry, thereby increasing the likelihood of opioid abuse and addiction

Effects of smoking on brain aging, 2

International Nuclear Information System (INIS)

Kubota, Kazuo; Matsuzawa, Taiju; Fujiwara, Takehiko

1985-01-01

Brain atrophy during normal aging and its relation to chronic smoking was studied using quantitative volumetric measurements of computed tomography. Study was performed about 159 smokers and 194 non-smokers with no neurological abnormality nor focal abnormality in CT scans. Each pixel of head CT scans was computed and Brain Volume Index (BVI) was calculated. BVI showed a significant decrease in smokers compared to non-smokers in three age groups, 50-to-54, 55-to-59 (p < 0.001, both) and 65-to-69 (p < 0.05). A dose-response study in the male showed that BVI in smokers was significantly lower than that for non smokers. Mean BVI tended to decrease when the smoking index increased but the trend was not significant. The systolic blood pressure and serum triglycrides of smokers were significantly higher than non-smokers (p < 0.002 and p < 0.05). It was suggested that age-related brain atrophy was enhanced by chronic smoking. Previously we showed that cerebral blood flow (CBF) was significantly lower in smokers than in non-smokers. Then, we suggest the following hypothesis; smoking chronically advances atherosclerosis, both atherosclerosis and high blood pressure reduce CBF, reduced CBF accelerated the lose of neurons which finally renders the brain atrophic. (author)

Brain urea increase is an early Huntington's disease pathogenic event observed in a prodromal transgenic sheep model and HD cases.

Science.gov (United States)

Handley, Renee R; Reid, Suzanne J; Brauning, Rudiger; Maclean, Paul; Mears, Emily R; Fourie, Imche; Patassini, Stefano; Cooper, Garth J S; Rudiger, Skye R; McLaughlan, Clive J; Verma, Paul J; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

2017-12-26

The neurodegenerative disorder Huntington's disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin ( HTT ) gene, translating to an elongated glutamine tract in the huntingtin protein. The pathogenic mechanism resulting in cell dysfunction and death beyond the causative mutation is not well defined. To further delineate the early molecular events in HD, we performed RNA-sequencing (RNA-seq) on striatal tissue from a cohort of 5-y-old OVT73 -line sheep expressing a human CAG-expansion HTT cDNA transgene. Our HD OVT73 sheep are a prodromal model and exhibit minimal pathology and no detectable neuronal loss. We identified significantly increased levels of the urea transporter SLC14A1 in the OVT73 striatum, along with other important osmotic regulators. Further investigation revealed elevated levels of the metabolite urea in the OVT73 striatum and cerebellum, consistent with our recently published observation of increased urea in postmortem human brain from HD cases. Extending that finding, we demonstrate that postmortem human brain urea levels are elevated in a larger cohort of HD cases, including those with low-level neuropathology (Vonsattel grade 0/1). This elevation indicates increased protein catabolism, possibly as an alternate energy source given the generalized metabolic defect in HD. Increased urea and ammonia levels due to dysregulation of the urea cycle are known to cause neurologic impairment. Taken together, our findings indicate that aberrant urea metabolism could be the primary biochemical disruption initiating neuropathogenesis in HD.

Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

International Nuclear Information System (INIS)

Choi, Hong-Seok; Choi, Yeong-Gon; Shin, Hae-Young; Oh, Jae-Min; Park, Jeong-Ho; Kim, Jae-Il; Carp, Richard I.; Choi, Eun-Kyoung; Kim, Yong-Sun

2014-01-01

Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the

Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

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Choi, Hong-Seok [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Choi, Yeong-Gon; Shin, Hae-Young; Oh, Jae-Min [Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Park, Jeong-Ho [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Kim, Jae-Il [Department of Food Science and Nutrition, Pukyong National University, 599-1 Daeyeon-3-dong, Nam-gu, Busan 608-737 (Korea, Republic of); Carp, Richard I. [New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 (United States); Choi, Eun-Kyoung, E-mail: ekchoi@hallym.ac.kr [Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Kim, Yong-Sun, E-mail: yskim@hallym.ac.kr [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of)

2014-05-30

Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the

Increased histone H3 phosphorylation in neurons in specific brain structures after induction of status epilepticus in mice.

Directory of Open Access Journals (Sweden)

Tetsuji Mori

Full Text Available Status epilepticus (SE induces pathological and morphological changes in the brain. Recently, it has become clear that excessive neuronal excitation, stress and drug abuse induce chromatin remodeling in neurons, thereby altering gene expression. Chromatin remodeling is a key mechanism of epigenetic gene regulation. Histone H3 phosphorylation is frequently used as a marker of chromatin remodeling and is closely related to the upregulation of mRNA transcription. In the present study, we analyzed H3 phosphorylation levels in vivo using immunohistochemistry in the brains of mice with pilocarpine-induced SE. A substantial increase in H3 phosphorylation was detected in neurons in specific brain structures. Increased H3 phosphorylation was dependent on neuronal excitation. In particular, a robust upregulation of H3 phosphorylation was detected in the caudate putamen, and there was a gradient of phosphorylated H3(+ (PH3(+ neurons along the medio-lateral axis. After unilateral ablation of dopaminergic neurons in the substantia nigra by injection of 6-hydroxydopamine, the distribution of PH3(+ neurons changed in the caudate putamen. Moreover, our histological analysis suggested that, in addition to the well-known MSK1 (mitogen and stress-activated kinase/H3 phosphorylation/c-fos pathway, other signaling pathways were also activated. Together, our findings suggest that a number of genes involved in the pathology of epileptogenesis are upregulated in PH3(+ brain regions, and that H3 phosphorylation is a suitable indicator of strong neuronal excitation.

Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia

Science.gov (United States)

Kim, Jae Hwan; Lee, Yong Woo; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

2010-01-01

Brain edema is frequently shown after cerebral ischemia. It is an expansion of brain volume because of increasing water content in brain. It causes to increase mortality after stroke. Agmatine, formed by the decarboxylation of -arginine by arginine decarboxylase, has been shown to be neuroprotective in trauma and ischemia models. The purpose of this study was to investigate the effect of agmatine for brain edema in ischemic brain damage and to evaluate the expression of aquaporins (AQPs). Results showed that agmatine significantly reduced brain swelling volume 22 h after 2 h middle cerebral artery occlusion in mice. Water content in brain tissue was clearly decreased 24 h after ischemic injury by agmatine treatment. Blood–brain barrier (BBB) disruption was diminished with agmatine than without. The expressions of AQPs-1 and -9 were well correlated with brain edema as water channels, were significantly decreased by agmatine treatment. It can thus be suggested that agmatine could attenuate brain edema by limitting BBB disruption and blocking the accumulation of brain water content through lessening the expression of AQP-1 after cerebral ischemia. PMID:20029450

Volumetric quantification of brain volume in children using sequential CT scans

International Nuclear Information System (INIS)

Hamano, K.; Iwasaki, N.; Kawashima, K.; Takita, H.

1990-01-01

We devised a three dimensional method for the accurate measurement of brain volume and applied it to 32 neurologically normal children, 7 children with only mental retardation and 15 children with both mental retardation and motor disturbance. In the group of neurologically normal children, the total brain volume increased from 723 cm 3 to 1407 cm 3 in order of age. The correlation ratio between the total brain volume and age was significant (P 00600.0001). The values of the total brain volume and the developmental curve were similar to those of the total brain weight of normal children previously reported. The combined volume of the cerebellum, the midbrain, the pons, and the medulla also increased from 76 cm 3 to 200 cm 3 in a manner similar to that of the total brain. The correlation between total brain volume and head circumference was significant (P<0.0001). In the group of children with mental retardation, the total brain volume was relatively smaller than that of neurologically normal children. In the group of the children with mental retardation and motor disturbance, 10 out of 15 cases showed values below -2 SD of those of neurologically normal children. The values of the total brain volume were each less than -3 SD in 3 cases whose head circumferences were each more than -3 SD. Our method for the direct measurement of brain volume based on serial CT scans may be useful for the accurate examination of brain development. (orig.)

Histamine Induces Alzheimer’s Disease-Like Blood Brain Barrier Breach and Local Cellular Responses in Mouse Brain Organotypic Cultures

Directory of Open Access Journals (Sweden)

Jonathan C. Sedeyn

2015-01-01

Full Text Available Among the top ten causes of death in the United States, Alzheimer’s disease (AD is the only one that cannot be cured, prevented, or even slowed down at present. Significant efforts have been exerted in generating model systems to delineate the mechanism as well as establishing platforms for drug screening. In this study, a promising candidate model utilizing primary mouse brain organotypic (MBO cultures is reported. For the first time, we have demonstrated that the MBO cultures exhibit increased blood brain barrier (BBB permeability as shown by IgG leakage into the brain parenchyma, astrocyte activation as evidenced by increased expression of glial fibrillary acidic protein (GFAP, and neuronal damage-response as suggested by increased vimentin-positive neurons occur upon histamine treatment. Identical responses—a breakdown of the BBB, astrocyte activation, and neuronal expression of vimentin—were then demonstrated in brains from AD patients compared to age-matched controls, consistent with other reports. Thus, the histamine-treated MBO culture system may provide a valuable tool in combating AD.

Impact of sex differences in brain response to infection with Plasmodium berghei.

Science.gov (United States)

Dkhil, Mohamed A; Al-Shaebi, Esam M; Lubbad, Mahmoud Y; Al-Quraishy, Saleh

2016-01-01

Malaria is considered to be one of the most prevalent diseases in the world. Severity of the disease between males and females is very important in clinical research areas. In this study, we investigated the impact of sex differences in brain response to infection with Plasmodium berghei. Male and female C57Bl/6 mice were infected with P. berghei-infected erythrocytes. The infection induced a significant change in weight loss in males (-7.2 % ± 0.5) than females (-4.9 % ± 0.6). The maximum parasitemia reached about 15 % at day 9 postinfection. Also, P. berghei infection caused histopathological changes in the brain of mice. These changes were in the form of inflammation, hemorrhage, and structural changes in Purkinje cells. In addition, P. berghei was able to induce a marked oxidative damage in mice brain. The infection induced a significant increase in male brain glutathione than females while the brain catalase level was significantly increased in infected females than infected males. Moreover, the change in brain neurotransmitters, dopamine, epinephrine, norepinephrine, and serotonin, was more in infected males than infected females. At the molecular level, P. berghei was able to induce upregulations of Adam23, Cabp1, Cacnb4, Glrb, and Vdac3-mRNA in the brain of mice. These genes were significantly upregulated in infected males than in infected females. In general, P. berghei could induce structural, biochemical, and molecular alterations in mice brain. Severity of these alterations was different according to sex of mice.

Brain renin angiotensin system in cardiac hypertrophy and failure

Directory of Open Access Journals (Sweden)

Luciana eCampos

2012-01-01

Full Text Available Brain renin-angiotensin system (RAS is significantly involved in the roles of the endocrine RAS in cardiovascular regulation. Our studies indicate that the brain RAS participates in the development of cardiac hypertrophy and fibrosis through sympathetic activation. Inhibition of sympathetic hyperactivity after myocardial infarction through suppression of the brain RAS appears beneficial. The brain RAS is involved in the modulation of circadian rhythms of arterial pressure, contributing to nondipping hypertension. We conclude that the brain RAS in pathophysiological states interacts synergistically with the chronically overactive RAS through a positive biofeedback in order to maintain a state of alert diseased conditions, such as cardiac hypertrophy and failure. Therefore, targeting brain RAS with drugs such as angiotensin converting inhibitors or receptor blockers having increased brain penetrability could be of advantage. These RAS-targeting drugs are first-line therapy for all heart failure patients. Since the RAS has both endocrine and local tissue components, RAS drugs are being developed to attain increased tissue penetrability and volume of distribution and consequently an efficient inhibition of both RAS components.

Effects of sevoflurane on adenylate cyclase and phosphodiesterases activity in brain of rats

International Nuclear Information System (INIS)

Feng Changdong; Yang Jianping; Dai Tijun

2009-01-01

Objective: To investigate the effects of sevoflurane on c adenylate cyclase (AC) and phosphodiesterases (PDE) activity in the cerebrocortex, hippocampus and brain stem of rats, and to examine the role of cAMP in sevoflurane anesthesia. Methods: Fourty SD rats were delaminately designed and allocated randomly to 5 groups inhaling 1.5% sevoflurane i.e., no recovery (recovery group, n=8) and one hour after righting reflexrecovery (aware group, n=8). The brain tissues were rapidly dissected into cerebrocortex and hippocampus and brain stem.Then the adenylate cyclase and phosphodiesterases activity were assessed. Results: So far as the activity of AC is concerned, compared with the control group, the activity of AC in the cerebrocortex, hippocampus and brain stem brain stem of induction group and anesthesia group, the cerebrocortex, and hippocampus in the recovery group were significantly increased; compared with those in the anesthesia group, the activity of AC in the cerebrocortex, hippocampus and brain stem of aware group were significantly decreased (P<0.05); For the activity of PDE, compared with the control group, the activity of PDE in the cerebrocortex, hippocampus and brain stem in the induction group and anesthesia group was significantly decreased, compared with that in anesthesia group, the activity of PDE in the cerebrocortex, hippocampus and brain stem of recovery group and aware group was significantly increased (P<0.05). Conclusion: cAMP may play an important role in sevoflurane anesthesia. (authors)

Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase 18F-FET PET accuracy without dynamic scans.

Science.gov (United States)

Lohmann, Philipp; Stoffels, Gabriele; Ceccon, Garry; Rapp, Marion; Sabel, Michael; Filss, Christian P; Kamp, Marcel A; Stegmayr, Carina; Neumaier, Bernd; Shah, Nadim J; Langen, Karl-Josef; Galldiks, Norbert

2017-07-01

We investigated the potential of textural feature analysis of O-(2-[ 18 F]fluoroethyl)-L-tyrosine ( 18 F-FET) PET to differentiate radiation injury from brain metastasis recurrence. Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamic 18 F-FET PET. Tumour-to-brain ratios (TBRs) of 18 F-FET uptake and 62 textural parameters were determined on summed images 20-40 min post-injection. Tracer uptake kinetics, i.e., time-to-peak (TTP) and patterns of time-activity curves (TAC) were evaluated on dynamic PET data from 0-50 min post-injection. Diagnostic accuracy of investigated parameters and combinations thereof to discriminate between brain metastasis recurrence and radiation injury was compared. Diagnostic accuracy increased from 81 % for TBR mean alone to 85 % when combined with the textural parameter Coarseness or Short-zone emphasis. The accuracy of TBR max alone was 83 % and increased to 85 % after combination with the textural parameters Coarseness, Short-zone emphasis, or Correlation. Analysis of TACs resulted in an accuracy of 70 % for kinetic pattern alone and increased to 83 % when combined with TBR max . Textural feature analysis in combination with TBRs may have the potential to increase diagnostic accuracy for discrimination between brain metastasis recurrence and radiation injury, without the need for dynamic 18 F-FET PET scans. • Textural feature analysis provides quantitative information about tumour heterogeneity • Textural features help improve discrimination between brain metastasis recurrence and radiation injury • Textural features might be helpful to further understand tumour heterogeneity • Analysis does not require a more time consuming dynamic PET acquisition.

Correlation Between Subacute Sensorimotor Deficits and Brain Edema in Rats after Surgical Brain Injury.

Science.gov (United States)

McBride, Devin W; Wang, Yuechun; Adam, Loic; Oudin, Guillaume; Louis, Jean-Sébastien; Tang, Jiping; Zhang, John H

2016-01-01

No matter how carefully a neurosurgical procedure is performed, it is intrinsically linked to postoperative deficits resulting in delayed healing caused by direct trauma, hemorrhage, and brain edema, termed surgical brain injury (SBI). Cerebral edema occurs several hours after SBI and is a major contributor to patient morbidity, resulting in increased postoperative care. Currently, the correlation between functional recovery and brain edema after SBI remains unknown. Here we examine the correlation between neurological function and brain water content in rats 42 h after SBI. SBI was induced in male Sprague-Dawley rats via frontal lobectomy. Twenty-four hours post-ictus animals were subjected to four neurobehavior tests: composite Garcia neuroscore, beam walking test, corner turn test, and beam balance test. Animals were then sacrificed for right-frontal brain water content measurement via the wet-dry method. Right-frontal lobe brain water content was found to significantly correlate with neurobehavioral deficits in the corner turn and beam balance tests: the number of left turns (percentage of total turns) for the corner turn test and distance traveled for the beam balance test were both inversely proportional with brain water content. No correlation was observed for the composite Garcia neuroscore or the beam walking test.

Alterations in diffusion and perfusion in the pathogenesis of peritumoral brain edema in meningiomas

International Nuclear Information System (INIS)

Bitzer, M.; Klose, U.; Naegele, T.; Voigt, K.; Geist-Barth, B.; Schick, F.; Claussen, C.D.; Morgalla, M.

2002-01-01

Magnetic resonance perfusion and diffusion studies were undertaken to clarify the significance of ischemia in the pathogenesis of peritumoral brain edema in patients with meningiomas. Included in this study were 26 patients with 27 meningiomas and 5 gliomas. Perfusion-weighted imaging (PWI) was performed using a gradient-echo, echo-planar-imaging (EPI) sequence for calculation of the relative regional cerebral blood volume (rrCBV) and the relative regional cerebral blood flow index (rrCBFi). Furthermore, multi-slice spin-echo EPI sequences were applied in order to obtain anisotropic and isotropic diffusion-weighted imaging (DWI). Apparent diffusion coefficient (ADC) values were then calculated for peritumoral brain parenchyma from tumors, with and without edema, using various diffusion sensitivities. Meningiomas without edema demonstrated a minimal increase of perfusion parameters in the peritumoral brain tissue. In contrast, cases with brain edema had highly significant (p 2 . The DWI showed a significantly larger ADC value within areas of brain edema, compared with the normal white matter (0.74 x 10 -3 vs 1.55 x 10 -3 mm 2 /s; p<0.0001). Increases in EI correlated with increases in ADC values. In 31% of the meningiomas associated with edema, areas with increased signal, probable ischemia, demonstrated significantly lower ADC values, in comparison with the rest of the edematous areas. These areas were confined to tissue immediately adjacent to the tumor. In general, the decrease in rrCBV in brain edema represents a consequence from, rather than a cause of, vasogenic edema. Ischemic alterations can be regarded as secondary, facultative phenomena in the pathogenesis of meningioma-related brain edema. (orig.)

Significance in the increase of women psychiatrists in Korea.

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Kim, Ha Kyoung; Kim, Soo In

2008-01-01

The number of female doctors has increased in Korea; 18.9% (13,083) of the total medical doctors registered (69,097) were women in 2006, compared to 13.6% (2,216) in 1975. The proportion of female doctors will jump up by 2010 considering that nearly 40% of the medical students are women as of today. This trend has had strong influence on the field of psychiatry; the percentage of women psychiatrists rose from 1.6 (6)% to 18% (453), from 1975 to 2006 and now women residents comprise 39% (206) of all. This is not only a reflection of a social phenomenon of the increase in professional women but also attributed to some specific characteristics of the psychiatry. Psychiatric practice may come more natural to women. While clinical activities of women psychiatrists are expanding, there are few women leaders and much less women are involving in academic activities in this field as yet. Though there is less sexual discrimination in the field of psychiatry, women psychiatrists are still having a lot of difficulties in balancing work and family matters. Many women psychiatrists also report they've ever felt an implied discrimination in their careers. In this study, we are to identify the characteristics of women psychiatrists and to explore the significance of the increase in women psychiatrists in Korea and the situation in which they are.

Brain size and white matter content of cerebrospinal tracts determine the upper cervical cord area: evidence from structural brain MRI

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Engl, Christina; Arsic, Milan; Boucard, Christine C.; Biberacher, Viola; Nunnemann, Sabine; Muehlau, Mark [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Technische Universitaet Muenchen, TUM-Neuroimaging Center, Klinikum rechts der Isar, Munich (Germany); Schmidt, Paul [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Ludwig-Maximilians-University Muenchen, Department of Statistics, Munich (Germany); Roettinger, Michael [Technische Universitaet Muenchen, Department of Radiology, Klinikum rechts der Isar, Munich (Germany); Muenchner Institut fuer Neuroradiologie, Munich (Germany); Etgen, Thorleif [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Klinikum Traunstein, Department of Neurology, Traunstein (Germany); Koutsouleris, Nikolaos; Meisenzahl, Eva M. [Ludwig-Maximilians-Universitaet Muenchen, Department of Psychiatry and Psychotherapy, Munich (Germany); Reiser, Maximilian [Ludwig-Maximilians-Universitaet, Department of Radiology, Munich (Germany)

2013-08-15

Measurement of the upper cervical cord area (UCCA) from brain MRI may be an effective way to quantify spinal cord involvement in neurological disorders such as multiple sclerosis. However, knowledge on the determinants of UCCA in healthy controls (HCs) is limited. In two cohorts of 133 and 285 HCs, we studied the influence of different demographic, body-related, and brain-related parameters on UCCA by simple and partial correlation analyses as well as by voxel-based morphometry (VBM) across both cerebral gray matter (GM) and white matter (WM). First, we confirmed the known but moderate effect of age on UCCA in the older cohort. Second, we studied the correlation of UCCA with sex, body height, and total intracranial volume (TIV). TIV was the only variable that correlated significantly with UCCA after correction for the other variables. Third, we studied the correlation of UCCA with brain-related parameters. Brain volume correlated stronger with UCCA than TIV. Both volumes of the brain tissue compartments GM and WM correlated with UCCA significantly. WM volume explained variance of UCCA after correction for GM volume, whilst the opposite was not observed. Correspondingly, VBM did not yield any brain region, whose GM content correlated significantly with UCCA, whilst cerebral WM content of cerebrospinal tracts strongly correlated with UCCA. This latter effect increased along a craniocaudal gradient. UCCA is mainly determined by brain volume as well as by WM content of cerebrospinal tracts. (orig.)

Inducing rat brain CYP2D with nicotine increases the rate of codeine tolerance; predicting the rate of tolerance from acute analgesic response.

Science.gov (United States)

McMillan, Douglas M; Tyndale, Rachel F

2017-12-01

Repeated opioid administration produces analgesic tolerance, which may lead to dose escalation. Brain CYP2D metabolizes codeine to morphine, a bioactivation step required for codeine analgesia. Higher brain, but not liver, CYP2D is found in smokers and nicotine induces rat brain, but not liver, CYP2D expression and activity. Nicotine induction of rat brain CYP2D increases acute codeine conversion to morphine, and analgesia, however the role of brain CYP2D on the effects of repeated codeine exposure and tolerance is unknown. Rats were pretreated with nicotine (brain CYP2D inducer; 1mg/kg subcutaneously) or vehicle (saline; 1ml/kg subcutaneously). Codeine (40-60mg/kg oral-gavage) or morphine (20-30mg/kg oral-gavage) was administered daily and analgesia was assessed daily using the tail-flick reflex assay. Nicotine (versus saline) pretreatment increased acute codeine analgesia (1.32-fold change in AUC 0-60 min ; pnicotine did not alter acute morphine analgesia (1.03-fold; p>0.8), or the rate of morphine tolerance (8.1%/day versus 7.6%; p>0.9). The rate of both codeine and morphine tolerance (loss in peak analgesia from day 1 to day 4) correlated with initial analgesic response on day 1 (R=0.97, p<001). Increasing brain CYP2D altered initial analgesia and subsequent rate of tolerance. Variation in an individual's initial response to analgesic (e.g. high initial dose, smoking) may affect the rate of tolerance, and thereby the risk for dose escalation and/or opioid dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of chronic hypoglycaemia on glucose concentration and glycogen content in rat brain: a localized 13C NMR study

OpenAIRE

Lei, Hongxia; Gruetter, Rolf

2006-01-01

While chronic hypoglycaemia has been reported to increase unidirectional glucose transport across the blood-brain barrier (BBB) and to increase GLUT1 expression at the endothelium, the effect on steady-state brain d-glucose and brain glycogen content is currently unknown. Brain glucose and glycogen concentrations were directly measured in vivo using localized 13C magnetic resonance spectroscopy (MRS) following 12-14 days of hypoglycaemia. Brain glucose content was significantly increased by 4...

Patent ductus arteriosus and brain volume

NARCIS (Netherlands)

Lemmers, Petra M A; Benders, Manon J N L; D'Ascenzo, Rita; Zethof, Jorine; Alderliesten, Thomas; Kersbergen, Karina J; Isgum, Ivana; de Vries, Linda S; Groenendaal, Floris; van Bel, Frank

2016-01-01

Background and Objectives: A hemodynamically significant patent ductus arteriosus (PDA) can compromise perfusion and oxygenation of the preterm brain. Reports suggest that PDA is associated with increased mortality and morbidity. We hypothesize that long-standing low cerebral oxygenation due to PDA

Enhancement of brain serotonin by long term oral administration of tryptophan produces no effect on food intake

International Nuclear Information System (INIS)

Haider, S.; Akhtar, N.; Kidwai, I.M.; Haleem, D.J.

1999-01-01

L-tryptophan (TRP) is widely used to enhance serotonin mediate brain functions. In the Present study effects of oral administration of TRP (100mg/kg) daily for 5 weeks, were investigated on the food intake, growth rate and brain indole amine metabolism in young rats. TRP ingestion significantly increased growth rate but did not alter food intake in rats. The levels of TRP and 5-hydroxytryptamine (5-HT) were higher in the hypothalamus of TRP treated rats. Increases of 5-hydroxyindole acetic acid (5-HIAA) were hot significant. TRP, 5-HT and 5-HIAA all increased in the rest of the brain of TRP treated rats. The present study shows that long term TRP administration thorough increases brain 5-ht metabolism and turnover but functional responses to 5-ht are not necessarily increases. (author)

Measurement of brain atrophy of aging using x-ray computed tomography

International Nuclear Information System (INIS)

Takeda, Shumpei; Matsuzawa, Taiju

1984-01-01

We measured brain volume of 1,045 subjects with no brain damage using x-ray computed tomography and investigated brain atrophy of aging. Severity of brain atrophy was estimated by brain atrophy index (BAI): BAI (%)=100 (%)x(cerebrospinal fluid space volume/cranial cavity volume). Atrophy of the brain began with statistical significance in the forties in both sexes. In males 40-49 years of age the mean BAI was 1.0% greater (p<0.001) and the S.D. of BAI was 1.1% greater (p<0.001) than those in their thirties. In females of 40-49 years the mean BAI was 0.5% greater (p<0.001) than that in their thirties, but there was no statistical significance between the two S.D.'s of both decades. The BAI increased exponentially with the increasing age from thirties in both sexes. Correlation coefficients were 0.702 (p< 0.001, n=471) in males and 0.721 (p<0.001, n=480) in females. From the regression coefficients it was calculated that the BAI was doubled in 19.4 years in males and 17.4 years in females after thirties. (author)

Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury

DEFF Research Database (Denmark)

Penkowa, Milena; Giralt, Mercedes; Lago, Natalia

2003-01-01

significantly increased up to but not including 20 dpl in the GFAP-IL6 mice. Oxidative stress as well as apoptotic cell death was significantly decreased throughout the time period studied in the GFAP-IL6 mice compared to controls. This could be linked to the altered inflammatory response as well......The effect of CNS-targeted IL-6 gene expression has been thoroughly investigated in the otherwise nonperturbed brain but not following brain injury. Here we examined the impact of astrocyte-targeted IL-6 production in a traumatic brain injury (cryolesion) model using GFAP-IL6 transgenic mice...... as to the transgenic IL-6-induced increase of the antioxidant, neuroprotective proteins metallothionein-I + II. These results indicate that although in the brain the chronic astrocyte-targeted expression of IL-6 spontaneously induces an inflammatory response causing significant damage, during an acute...

Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization.

Directory of Open Access Journals (Sweden)

Daniel Y Joh

Full Text Available Successful treatment of brain tumors such as glioblastoma multiforme (GBM is limited in large part by the cumulative dose of Radiation Therapy (RT that can be safely given and the blood-brain barrier (BBB, which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs. GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ~1.3. Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature.

Contrast enhancement in EIT imaging of the brain

International Nuclear Information System (INIS)

Nissinen, A; Kaipio, J P; Vauhkonen, M; Kolehmainen, V

2016-01-01

We consider electrical impedance tomography (EIT) imaging of the brain. The brain is surrounded by the poorly conducting skull which has low conductivity compared to the brain. The skull layer causes a partial shielding effect which leads to weak sensitivity for the imaging of the brain tissue. In this paper we propose an approach based on the Bayesian approximation error approach, to enhance the contrast in brain imaging. With this approach, both the (uninteresting) geometry and the conductivity of the skull are embedded in the approximation error statistics, which leads to a computationally efficient algorithm that is able to detect features such as internal haemorrhage with significantly increased sensitivity and specificity. We evaluate the approach with simulations and phantom data. (paper)

Contrast enhancement in EIT imaging of the brain.

Science.gov (United States)

Nissinen, A; Kaipio, J P; Vauhkonen, M; Kolehmainen, V

2016-01-01

We consider electrical impedance tomography (EIT) imaging of the brain. The brain is surrounded by the poorly conducting skull which has low conductivity compared to the brain. The skull layer causes a partial shielding effect which leads to weak sensitivity for the imaging of the brain tissue. In this paper we propose an approach based on the Bayesian approximation error approach, to enhance the contrast in brain imaging. With this approach, both the (uninteresting) geometry and the conductivity of the skull are embedded in the approximation error statistics, which leads to a computationally efficient algorithm that is able to detect features such as internal haemorrhage with significantly increased sensitivity and specificity. We evaluate the approach with simulations and phantom data.

Minocycline causes widespread cell death and increases microglial labeling in the neonatal mouse brain.

Science.gov (United States)

Strahan, J Alex; Walker, William H; Montgomery, Taylor R; Forger, Nancy G

2017-06-01

Minocycline, an antibiotic of the tetracycline family, inhibits microglia in many paradigms and is among the most commonly used tools for examining the role of microglia in physiological processes. Microglia may play an active role in triggering developmental neuronal cell death, although findings have been contradictory. To determine whether microglia influence developmental cell death, we treated perinatal mice with minocycline (45 mg/kg) and quantified effects on dying cells and microglial labeling using immunohistochemistry for activated caspase-3 (AC3) and ionized calcium-binding adapter molecule 1 (Iba1), respectively. Contrary to our expectations, minocycline treatment from embryonic day 18 to postnatal day (P)1 caused a > tenfold increase in cell death 8 h after the last injection in all brain regions examined, including the primary sensory cortex, septum, hippocampus and hypothalamus. Iba1 labeling was also increased in most regions. Similar effects, although of smaller magnitude, were seen when treatment was delayed to P3-P5. Minocycline treatment from P3 to P5 also decreased overall cell number in the septum at weaning, suggesting lasting effects of the neonatal exposure. When administered at lower doses (4.5 or 22.5 mg/kg), or at the same dose 1 week later (P10-P12), minocycline no longer increased microglial markers or cell death. Taken together, the most commonly used microglial "inhibitor" increases cell death and Iba1 labeling in the neonatal mouse brain. Minocycline is used clinically in infant and pediatric populations; caution is warrented when using minocycline in developing animals, or extrapolating the effects of this drug across ages. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 753-766, 2017. © 2016 Wiley Periodicals, Inc.

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

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Nishiwaki, Shinichi

1988-06-01

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

Effects of Exercise Following Lateral Fluid Percussion Brain Injury in Rats.

Science.gov (United States)

Hicks, Ramona R.; Boggs, Arden; Leider, Denise; Kraemer, Philip; Brown, Russell; Scheff, Stephen W.; Seroogy, Kim B.

1998-01-01

Previous studies have suggested that brain-derived neurotrophic factor (BDNF) is involved in memory and learning, and may be neuroprotective following various brain insults. Exercise has been found to increase BDNF mRNA levels in various brain regions, including specific subpopulations of hippocampal neurons. In the present study, we were interested in whether following traumatic brain injury, exercise could increase BDNF mRNA expression, attenuate neuropathology, and improve cognitive and neuromoter performance. We subjected adult male Sprague-Dawley rats to a fluid percussion brain injury, followed by either 18 days of treadmill exercise or handling. Spatial memory was evaluated in a Morris Water Maze (MWM) and motor function was evaluated with a battery of neuromotor tests. Neuropathology was evaluated by measuring the cortical lesion volume and the extent of neuronal loss in the hipocampus. Expression of BDNF mRNA in the hippocampus was assessed with in situ hybridization and densitometry. Hybridization signal for BDNF mRNA was significantly increased bilaterally in the exercise group in hippocampal regions CA1 and CA3 (p<0.05), but not in the granule cell layer of the dentate gyrus. No significant differences were observed between the groups in neuropathology, spatial memory, or motor performance. This study suggests that after traumatic brain injury, exercise elevates BDNF mRNA in specific regions of the hippocampus.

Carnosine supplementation protects rat brain tissue against ethanol-induced oxidative stress.

Science.gov (United States)

Ozel Turkcu, Ummuhani; Bilgihan, Ayşe; Biberoglu, Gursel; Mertoglu Caglar, Oznur

2010-06-01

Ethanol causes oxidative stress and tissue damage. The aim of this study was to investigate the effect of antioxidant carnosine on the oxidative stress induced by ethanol in the rat brain tissue. Forty male rats were divided equally into four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals were sacrificed using ketamine and brain tissues were removed. Malondialdehyde (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain tissue specimens were significantly increased in the CAR and EtOH groups when compared to the control animals. MDA and PCO levels in the EtOH group were significantly increased as compared to the other groups (P < 0.05). CAR treatment also decreased MDA levels in the CAR group as compared to the control group. Increased SOD activities were obtained in the EtOH + CAR group as compared to the control (P < 0.05). CAR levels in the rat brain were significantly increased in the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These findings indicated that carnosine may appear as a protective agent against ethanol-induced brain damage.

Asymptomatic brain tumor detected at brain check-up

International Nuclear Information System (INIS)

Onizuka, Masanari; Suyama, Kazuhiko; Shibayama, Akira; Hiura, Tsuyoshi; Horie, Nobutaka; Miyazaki, Hisaya

2001-01-01

Brain check-up was performed in 4000 healthy subjects who underwent medical and radiological examinations for possible brain diseases in our hospital from April 1996 to March 2000. Magnetic resonance imaging revealed 11 brain tumors which consisted of six meningiomas, three pituitary adenomas, one astrocytoma, and one epidermoid cyst. The detection rate of incidental brain tumor in our hospital was 0.3%. Nine patients underwent surgery, with one case of morbidity due to postoperative transient oculomotor nerve paresis. The widespread use of brain check-up may increasingly detect asymptomatic brain tumors. Surgical indications for such lesions remain unclear, and the strategy for treatment should be determined with consideration of the patient's wishes. (author)

Training leads to increased auditory brain-computer interface performance of end-users with motor impairments.

Science.gov (United States)

Halder, S; Käthner, I; Kübler, A

2016-02-01

Auditory brain-computer interfaces are an assistive technology that can restore communication for motor impaired end-users. Such non-visual brain-computer interface paradigms are of particular importance for end-users that may lose or have lost gaze control. We attempted to show that motor impaired end-users can learn to control an auditory speller on the basis of event-related potentials. Five end-users with motor impairments, two of whom with additional visual impairments, participated in five sessions. We applied a newly developed auditory brain-computer interface paradigm with natural sounds and directional cues. Three of five end-users learned to select symbols using this method. Averaged over all five end-users the information transfer rate increased by more than 1800% from the first session (0.17 bits/min) to the last session (3.08 bits/min). The two best end-users achieved information transfer rates of 5.78 bits/min and accuracies of 92%. Our results show that an auditory BCI with a combination of natural sounds and directional cues, can be controlled by end-users with motor impairment. Training improves the performance of end-users to the level of healthy controls. To our knowledge, this is the first time end-users with motor impairments controlled an auditory brain-computer interface speller with such high accuracy and information transfer rates. Further, our results demonstrate that operating a BCI with event-related potentials benefits from training and specifically end-users may require more than one session to develop their full potential. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Progressive increase in brain glucose metabolism after intrathecal administration of autologous mesenchymal stromal cells in patients with diffuse axonal injury.

Science.gov (United States)

Vaquero, Jesús; Zurita, Mercedes; Bonilla, Celia; Fernández, Cecilia; Rubio, Juan J; Mucientes, Jorge; Rodriguez, Begoña; Blanco, Edelio; Donis, Luis

2017-01-01

Cell therapy in neurological disability after traumatic brain injury (TBI) is in its initial clinical stage. We describe our preliminary clinical experience with three patients with diffuse axonal injury (DAI) who were treated with intrathecal administration of autologous mesenchymal stromal cells (MSCs). Three patients with established neurological sequelae due to DAI received intrathecally autologous MSCs. The total number of MSCs administered was 60 × 10 6 (one patient), 100 × 10 6 (one patient) and 300 × 10 6 (one patient). All three patients showed improvement after cell therapy, and subsequent studies with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) showed a diffuse and progressive increase in brain glucose metabolism. Our present results suggest benefit of intrathecal administration of MSCs in patients with DAI, as well as a relationship between this type of treatment and increase in brain glucose metabolism. These preliminary findings raise the question of convenience of assessing the potential benefit of intrathecal administration of MSCs for brain diseases in which a decrease in glucose metabolism represents a crucial pathophysiological finding, such as Alzheimer's disease (AD) and other dementias. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Alpha-synuclein gene ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipids

DEFF Research Database (Denmark)

Golovko, Mikhail Y; Rosenberger, Thad A; Feddersen, Søren

2007-01-01

Previously, we demonstrated that ablation of alpha-synuclein (Snca) reduces arachidonate (20:4n-6) turnover in brain phospholipids through modulation of an endoplasmic reticulum-localized acyl-CoA synthetase (Acsl). The effect of Snca ablation on docosahexaenoic acid (22:6n-3) metabolism is unknown...... and turnover in ethanolamine glycerophospholipid, phosphatidylserine, and phosphatidylinositol pools. Increased 22:6n-3-CoA mass was not the result of altered Acsl activity, which was unaffected by the absence of Snca. While Snca bound 22:6n-3, Kd = 1.0 +/- 0.5 micromol/L, it did not bind 22:6n-3-Co...

The effect of electromagnetic radiation on the rat brain: an experimental study.

Science.gov (United States)

Eser, Olcay; Songur, Ahmet; Aktas, Cevat; Karavelioglu, Ergun; Caglar, Veli; Aylak, Firdevs; Ozguner, Fehmi; Kanter, Mehmet

2013-01-01

The aim of this study is to determine the structural changes of electromagnetic waves in the frontal cortex, brain stem and cerebellum. 24 Wistar Albino adult male rats were randomly divided into four groups: group I consisted of control rats, and groups II-IV comprised electromagnetically irradiated (EMR) with 900, 1800 and 2450 MHz. The heads of the rats were exposed to 900, 1800 and 2450 MHz microwaves irradiation for 1h per day for 2 months. While the histopathological changes in the frontal cortex and brain stem were normal in the control group, there were severe degenerative changes, shrunken cytoplasm and extensively dark pyknotic nuclei in the EMR groups. Biochemical analysis demonstrated that the Total Antioxidative Capacity level was significantly decreased in the EMR groups and also Total Oxidative Capacity and Oxidative Stress Index levels were significantly increased in the frontal cortex, brain stem and cerebellum. IL-1β level was significantly increased in the EMR groups in the brain stem. EMR causes to structural changes in the frontal cortex, brain stem and cerebellum and impair the oxidative stress and inflammatory cytokine system. This deterioration can cause to disease including loss of these areas function and cancer development.

Increased Brain Perfusion Persists over the First Month of Life in Term Asphyxiated Newborns Treated with Hypothermia: Does it Reflect Activated Angiogenesis?

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Shaikh, Henna; Lechpammer, Mirna; Jensen, Frances E; Warfield, Simon K; Hansen, Anne H; Kosaras, Bela; Shevell, Michael; Wintermark, Pia

2015-06-01

Many asphyxiated newborns still develop brain injury despite hypothermia therapy. The development of brain injury in these newborns has been related partly to brain perfusion abnormalities. The purposes of this study were to assess brain hyperperfusion over the first month of life in term asphyxiated newborns and to search for some histopathological clues indicating whether this hyperperfusion may be related to activated angiogenesis following asphyxia. In this prospective cohort study, regional cerebral blood flow was measured in term asphyxiated newborns treated with hypothermia around day 10 of life and around 1 month of life using magnetic resonance imaging (MRI) and arterial spin labeling. A total of 32 MRI scans were obtained from 24 term newborns. Asphyxiated newborns treated with hypothermia displayed an increased cerebral blood flow in the injured brain areas around day 10 of life and up to 1 month of life. In addition, we looked at the histopathological clues in a human asphyxiated newborn and in a rat model of neonatal encephalopathy. Vascular endothelial growth factor (VEGF) was expressed in the injured brain of an asphyxiated newborn treated with hypothermia in the first days of life and of rat pups 24-48 h after the hypoxic-ischemic event, and the endothelial cell count increased in the injured cortex of the pups 7 and 11 days after hypoxia-ischemia. Our data showed that the hyperperfusion measured by imaging persisted in the injured areas up to 1 month of life and that angiogenesis was activated in the injured brain of asphyxiated newborns.

Increased superior frontal gyrus activation during working memory processing in psychosis: Significant relation to cumulative antipsychotic medication and to negative symptoms.

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Vogel, Tobias; Smieskova, Renata; Schmidt, André; Walter, Anna; Harrisberger, Fabienne; Eckert, Anne; Lang, Undine E; Riecher-Rössler, Anita; Graf, Marc; Borgwardt, Stefan

2016-08-01

Impairment in working memory (WM) is a core symptom in schizophrenia. However, little is known about how clinical features influence functional brain activity specific to WM processing during the development of first-episode psychosis (FEP) to schizophrenia (SZ). We compared functional WM-specific brain activity in FEP and SZ patients, including the effects of the duration of illness, psychopathological factors and antipsychotic medication. Cross-sectional study of male FEP (n=22) and SZ (n=20) patients performing an n-back task when undergoing functional magnetic resonance imaging (fMRI). Clinical features were collected by semi-structured interviews and medical records. The SZ group performed significantly worse than the FEP group in the 2-back condition. The SZ group also showed significantly higher activation in the left superior frontal gyrus in the 2-back versus 0-back condition (2-back>0-back). This frontal activation correlated positively with negative symptoms and with cumulative antipsychotic medication during the year before the fMRI examination. There were no significant correlations between activation and duration of illness. There was greater frontal neural activation in SZ than in FEP. This indicated differences in WM processing, and was significantly related to cumulative antipsychotic exposure and negative symptoms, but not to the duration of illness. Copyright © 2016 Elsevier B.V. All rights reserved.

[Brain oedema and acute liver failure].

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Spahr, L

2003-04-01

Brain oedema leading to intracranial hypertension occurs in a significant proportion of patients with acute liver failure in whom it is a leading cause of death. Although precise pathogenic mechanisms associated to this severe complication remain incompletely understood, increasing evidence points to gut-derived neurotoxins including ammonia as key mediators in cerebral osmotic and perfusion disturbances. The management of brain oedema and intracranial hypertension requires a multidisciplinar approach in a center where liver transplantation is available, as this option is the only treatment modality that provides improvement in outcome. This article reviews the most common causes of acute liver failure and the standard of supportive care management, and describes future potential therapeutic aspects of brain oedema and intracranial hypertension.

Acetylcholine turnover in mouse brain: influence of cholinesterase inhibitors

International Nuclear Information System (INIS)

Karlen, B.; Holmstedt, B.; Lundgren, G.; Lundin, J.

1986-01-01

The authors determine whether the irreversible cholinesterase inhibitors soman, sarin or FX, which are thought to increase brain ACh concentration by a mechanism different to that of the muscarinic receptor agonist oxotremorine, also would decrease the turnover rate of brain ACh. Male albino mice were used in the study. N-(2-hydroxyethyl-N,N,N-tri-( 2 H 3 )methylammonium iodide and N-(2-acetoxyethyl)-N,N,N-tri-( 2 H 3 )methylammonium iodide were used as internal standards. N-(2-acetoxyethyl)-N,N,N,-tri-( 2 H 3 ), ( 1 H)methylammonium iodide was used for calibration purposes. The concentrations of Ch, ACh and their deuterated variants found in whole brain and striatum after pretreatment with saline, soman, sarin and FX are shown. In whole brain the endogeneous concentration of Ach was not affected by sarin and only to a slight but significant extent by Fs, while soman increased the level to about 30 nmol/g. All three substances increased the ch level in comparison to controls

The Influence of the Brain on Overpopulation, Ageing and Dependency.

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Cape, Ronald D. T.

1989-01-01

With time, an increasing number in the world population is becoming old, and changes in the aging brain mean that a significant proportion of the aged are likely to be dependent on others. The devotion of resources to research into the aging brain could bring benefits far outweighing the investment. (Author/CW)

Elevated endogenous erythropoietin concentrations are associated with increased risk of brain damage in extremely preterm neonates.

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Steven J Korzeniewski

Full Text Available We sought to determine, in very preterm infants, whether elevated perinatal erythropoietin (EPO concentrations are associated with increased risks of indicators of brain damage, and whether this risk differs by the co-occurrence or absence of intermittent or sustained systemic inflammation (ISSI.Protein concentrations were measured in blood collected from 786 infants born before the 28th week of gestation. EPO was measured on postnatal day 14, and 25 inflammation-related proteins were measured weekly during the first 2 postnatal weeks. We defined ISSI as a concentration in the top quartile of each of 25 inflammation-related proteins on two separate days a week apart. Hypererythropoietinemia (hyperEPO was defined as the highest quartile for gestational age on postnatal day 14. Using logistic regression and multinomial logistic regression models, we compared risks of brain damage among neonates with hyperEPO only, ISSI only, and hyperEPO+ISSI, to those who had neither hyperEPO nor ISSI, adjusting for gestational age.Newborns with hyperEPO, regardless of ISSI, were more than twice as likely as those without to have very low (< 55 Mental (OR 2.3; 95% CI 1.5-3.5 and/or Psychomotor (OR 2.4; 95% CI 1.6-3.7 Development Indices (MDI, PDI, and microcephaly at age two years (OR 2.4; 95%CI 1.5-3.8. Newborns with both hyperEPO and ISSI had significantly increased risks of ventriculomegaly, hemiparetic cerebral palsy, microcephaly, and MDI and PDI < 55 (ORs ranged from 2.2-6.3, but not hypoechoic lesions or other forms of cerebral palsy, relative to newborns with neither hyperEPO nor ISSI.hyperEPO, regardless of ISSI, is associated with elevated risks of very low MDI and PDI, and microcephaly, but not with any form of cerebral palsy. Children with both hyperEPO and ISSI are at higher risk than others of very low MDI and PDI, ventriculomegaly, hemiparetic cerebral palsy, and microcephaly.

Whole brain functional connectivity in clinically isolated syndrome without conventional brain MRI lesions

International Nuclear Information System (INIS)

Liu, Yaou; Dai, Zhengjia; Duan, Yunyun; Huang, Jing; Ren, Zhuoqiong; Li, Kuncheng; Liu, Zheng; Dong, Huiqing; Shu, Ni; He, Yong; Vrenken, Hugo; Wattjes, Mike P.; Barkhof, Frederik

2016-01-01

To investigate brain functional connectivity (FC) alterations in patients with clinically isolated syndromes (CIS) presenting without conventional brain MRI lesions, and to identify the FC differences between the CIS patients who converted to multiple sclerosis (MS) and those not converted during a 5-year follow-up. We recruited 20 CIS patients without conventional brain lesions, 28 patients with MS and 28 healthy controls (HC). Normalized voxel-based functional connectivity strength (nFCS) was determined using resting-state fMRI (R-fMRI) and compared among groups. Furthermore, 5-years clinical follow-up of the CIS patients was performed to examine the differences in nFCS between converters and non-converters. Compared to HC, CIS patients showed significantly decreased nFCS in the visual areas and increased nFCS in several brain regions predominately in the temporal lobes. MS patients revealed more widespread higher nFCS especially in deep grey matter (DGM), compared to CIS and HC. In the four CIS patients converting to MS, significantly higher nFCS was found in right anterior cingulate gyrus (ACC) and fusiform gyrus (FG), compared to non-converted patients. We demonstrated both functional impairment and compensation in CIS by R-fMRI. nFCS alteration in ACC and FG seems to occur in CIS patients at risk of developing MS. (orig.)

Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase {sup 18}F-FET PET accuracy without dynamic scans

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Lohmann, Philipp; Stoffels, Gabriele; Stegmayr, Carina; Neumaier, Bernd [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); Ceccon, Garry [University of Cologne, Department of Neurology, Cologne (Germany); Rapp, Marion; Sabel, Michael; Kamp, Marcel A. [Heinrich Heine University Duesseldorf, Department of Neurosurgery, Duesseldorf (Germany); Filss, Christian P. [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); RWTH Aachen University Hospital, Department of Nuclear Medicine, Aachen (Germany); Shah, Nadim J. [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); RWTH Aachen University Hospital, Department of Neurology, Aachen (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Department of Neurology, Juelich (Germany); Langen, Karl-Josef [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); RWTH Aachen University Hospital, Department of Nuclear Medicine, Aachen (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Department of Neurology, Juelich (Germany); Galldiks, Norbert [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); University of Cologne, Department of Neurology, Cologne (Germany); University of Cologne, Center of Integrated Oncology (CIO), Cologne (Germany)

2017-07-15

We investigated the potential of textural feature analysis of O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine ({sup 18}F-FET) PET to differentiate radiation injury from brain metastasis recurrence. Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamic {sup 18}F-FET PET. Tumour-to-brain ratios (TBRs) of {sup 18}F-FET uptake and 62 textural parameters were determined on summed images 20-40 min post-injection. Tracer uptake kinetics, i.e., time-to-peak (TTP) and patterns of time-activity curves (TAC) were evaluated on dynamic PET data from 0-50 min post-injection. Diagnostic accuracy of investigated parameters and combinations thereof to discriminate between brain metastasis recurrence and radiation injury was compared. Diagnostic accuracy increased from 81 % for TBR{sub mean} alone to 85 % when combined with the textural parameter Coarseness or Short-zone emphasis. The accuracy of TBR{sub max} alone was 83 % and increased to 85 % after combination with the textural parameters Coarseness, Short-zone emphasis, or Correlation. Analysis of TACs resulted in an accuracy of 70 % for kinetic pattern alone and increased to 83 % when combined with TBR{sub max}. Textural feature analysis in combination with TBRs may have the potential to increase diagnostic accuracy for discrimination between brain metastasis recurrence and radiation injury, without the need for dynamic {sup 18}F-FET PET scans. (orig.)

Increased brain damage after ischaemic stroke in mice lacking the chemokine receptor CCR5

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Sorce, S; Bonnefont, J; Julien, S; Marq-Lin, N; Rodriguez, I; Dubois-Dauphin, M; Krause, KH

2010-01-01

Background and purpose: The chemokine receptor CCR5 is well known for its function in immune cells; however, it is also expressed in the brain, where its specific role remains to be elucidated. Because genetic factors may influence the risk of developing cerebral ischaemia or affect its clinical outcome, we have analysed the role of CCR5 in experimental stroke. Experimental approach: Permanent cerebral ischaemia was performed by occlusion of the middle cerebral artery in wild-type and CCR5-deficient mice. Locomotor behaviour, infarct size and histochemical alterations were analysed at different time points after occlusion. Key results: The cerebral vasculature was comparable in wild-type and CCR5-deficient mice. However, the size of the infarct and the motor deficits after occlusion were markedly increased in CCR5-deficient mice as compared with wild type. No differences between wild-type and CCR5-deficient mice were elicited by occlusion with respect to the morphology and abundance of astrocytes and microglia. Seven days after occlusion the majority of CCR5-deficient mice displayed neutrophil invasion in the infarct region, which was not observed in wild type. As compared with wild type, the infarct regions of CCR5-deficient mice were characterized by increased neuronal death. Conclusions and implications: Lack of CCR5 increased the severity of brain injury following occlusion of the middle cerebral artery. This is of particular interest with respect to the relatively frequent occurrence of CCR5 deficiency in the human population (1–2% of the Caucasian population) and the advent of CCR5 inhibitors as novel drugs. PMID:20423342

Personal significance is encoded automatically by the human brain: an event-related potential study with ringtones.

Science.gov (United States)

Roye, Anja; Jacobsen, Thomas; Schröger, Erich

2007-08-01

In this human event-related brain potential (ERP) study, we have used one's personal--relative to another person's--ringtone presented in a two-deviant passive oddball paradigm to investigate the long-term memory effects of self-selected personal significance of a sound on the automatic deviance detection and involuntary attention system. Our findings extend the knowledge of long-term effects usually reported in group-approaches in the domains of speech, music and environmental sounds. In addition to the usual mismatch negativity (MMN) and P3a component elicited by deviants in contrast to standard stimuli, we observed a posterior ERP deflection directly following the MMN for the personally significant deviant only. This specific impact of personal significance started around 200 ms after sound onset and involved neural generators that were different from the mere physical deviance detection mechanism. Whereas the early part of the P3a component was unaffected by personal significance, the late P3a was enhanced for the ERPs to the personal significant deviant suggesting that this stimulus was more powerful in attracting attention involuntarily. Following the involuntary attention switch, the personally significant stimulus elicited a widely-distributed negative deflection, probably reflecting further analysis of the significant sound involving evaluation of relevance or reorienting to the primary task. Our data show, that the personal significance of mobile phone and text message technology, which have developed as a major medium of communication in our modern world, prompts the formation of individual memory representations, which affect the processing of sounds that are not in the focus of attention.

A prospective study to evaluate a new residential community reintegration programme for severe chronic brain injury: the Brain Integration Programme.

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Geurtsen, G J; Martina, J D; Van Heugten, C M; Geurts, A C H

2008-07-01

To assess the effectiveness of a residential community reintegration programme for participants with chronic sequelae of severe acquired brain injury that hamper community functioning. Prospective cohort study. Twenty-four participants with acquired brain injury (traumatic n = 18; stroke n = 3, tumour n = 2, encephalitis n = 1). Participants had impaired illness awareness, alcohol and drug problems and/or behavioural problems. A skills-oriented programme with modules related to independent living, work, social and emotional well-being. The Community Integration Questionnaire, CES-Depression, EuroQOL, Employability Rating Scale, living situation and work status were scored at the start (T0), end of treatment (T1) and 1-year follow-up (T2). Significant effects on the majority of outcome measures were present at T1. Employability significantly improved at T2 and living independently rose from 42% to over 70%. Participants working increased from 38% to 58% and the hours of work per week increased from 8 to 15. The Brain Integration Programme led to a sustained reduction in experienced problems and improved community integration. It is concluded that even participants with complex problems due to severe brain injury who got stuck in life could improve their social participation and emotional well-being through a residential community reintegration programme.

Augmenting brain metabolism to increase macro- and chaperone-mediated autophagy for decreasing neuronal proteotoxicity and aging.

Science.gov (United States)

Loos, Ben; Klionsky, Daniel J; Wong, Esther

2017-09-01

Accumulation of toxic protein aggregates in the nerve cells is a hallmark of neuronal diseases and brain aging. Mechanisms to enhance neuronal surveillance to improve neuronal proteostasis have a direct impact on promoting neuronal health and forestalling age-related decline in brain function. Autophagy is a lysosomal degradative pathway pivotal for neuronal protein quality control. Different types of autophagic mechanisms participate in protein handling in neurons. Macroautophagy targets misfolded and aggregated proteins in autophagic vesicles to the lysosomes for destruction, while chaperone-mediated autophagy (CMA) degrades specific soluble cytosolic proteins delivered to the lysosomes by chaperones. Dysfunctions in macroautophagy and CMA contribute to proteo- and neuro-toxicity associated with neurodegeneration and aging. Thus, augmenting or preserving both autophagic mechanisms pose significant benefits in delaying physiological and pathological neuronal demises. Recently, life-style interventions that modulate metabolite ketone bodies, energy intake by caloric restriction and energy expenditure by exercise have shown to enhance both autophagy and brain health. However, to what extent these interventions affect neuronal autophagy to promote brain fitness remains largely unclear. Here, we review the functional connections of how macroautophagy and CMA are affected by ketone bodies, caloric restriction and exercise in the context of neurodegeneration. A concomitant assessment of yeast Saccharomyces cerevisiae is performed to reveal the conserved nature of such autophagic responses to substrate perturbations. In doing so, we provide novel insights and integrated evidence for a potential adjuvant therapeutic strategy to intervene in the neuronal decline in neurodegenerative diseases by controlling both macroautophagy and CMA fluxes favorably. Copyright © 2017 Elsevier Ltd. All rights reserved.

Residential Radon and Brain Tumour Incidence in a Danish Cohort

DEFF Research Database (Denmark)

Bräuner, Elvira V.; Andersen, Zorana J.; Andersen, Claus Erik

2013-01-01

Background: Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective: To investigate the long-term effect of expo...... significant associations and exposure-response patterns between long-term residential radon exposure radon in a general population and risk of primary brain tumours, adding new knowledge to this field. This finding could be chance and needs to be challenged in future studies.......Background: Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective: To investigate the long-term effect...... of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort. Methods: During 1993–1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced...

The effect of the cranial bone CT numbers on the brain CT numbers

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Fukuda, Hitoshi; Kobayashi, Shotai; Koide, Hiromi; Yamaguchi, Shuhei; Okada, Kazunori; Shimote, Koichi; Tsunematsu, Tokugoro (Shimane Medical Univ., Izumo (Japan))

1989-06-01

The effects of the cranial size and the computed tomography (CT) numbers of the cranial bone on that of the brain were studied in 70 subjects, aged from 30 to 94 years. The subjects had no histories of cerebrovascular accidents and showed no abnormalities in the central nervous system upon physical examinations and a CT scan. We measured the average attenuation values (CT numbers) of each elliptical region (165 pixels, 0.39 cm{sup 2}) at the bilateral thalamus and at twelve areas of the deep white matter. Multiple regression analysis was used to assess the effects of age, cranial size, and cranial bone CT numbers on the brain CT numbers. The effect of the cranial bone CT numbers on the brain CT numbers was statistically significant. The brain CT numbers increased with the increase in the cranial bone CT numbers. There was, however, no significant correlation between brain CT numbers and cranial size. In measuring the brain CT numbers, it is desirable that consideration be given to the cranial bone CT numbers. (author).

Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8).

Science.gov (United States)

Rodrigues, Tiago B; Ceballos, Ainhoa; Grijota-Martínez, Carmen; Nuñez, Barbara; Refetoff, Samuel; Cerdán, Sebastian; Morte, Beatriz; Bernal, Juan

2013-01-01

Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3) transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13)C) glucose and brain extracts prepared and analyzed by (13)C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.

Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8.

Directory of Open Access Journals (Sweden)

Tiago B Rodrigues

Full Text Available Mutations of the monocarboxylate transporter 8 (MCT8 cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3 transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13C glucose and brain extracts prepared and analyzed by (13C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.

Altered whole-brain connectivity in albinism.

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Welton, Thomas; Ather, Sarim; Proudlock, Frank A; Gottlob, Irene; Dineen, Robert A

2017-02-01

Albinism is a group of congenital disorders of the melanin synthesis pathway. Multiple ocular, white matter and cortical abnormalities occur in albinism, including a greater decussation of nerve fibres at the optic chiasm, foveal hypoplasia and nystagmus. Despite this, visual perception is largely preserved. It was proposed that this may be attributable to reorganisation among cerebral networks, including an increased interhemispheric connectivity of the primary visual areas. A graph-theoretic model was applied to explore brain connectivity networks derived from resting-state functional and diffusion-tensor magnetic resonance imaging data in 23 people with albinism and 20 controls. They tested for group differences in connectivity between primary visual areas and in summary network organisation descriptors. Main findings were supplemented with analyses of control regions, brain volumes and white matter microstructure. Significant functional interhemispheric hyperconnectivity of the primary visual areas in the albinism group were found (P = 0.012). Tests of interhemispheric connectivity based on the diffusion-tensor data showed no significant group difference (P = 0.713). Second, it was found that a range of functional whole-brain network metrics were abnormal in people with albinism, including the clustering coefficient (P = 0.005), although this may have been driven partly by overall differences in connectivity, rather than reorganisation. Based on the results, it was suggested that changes occur in albinism at the whole-brain level, and not just within the visual processing pathways. It was proposed that their findings may reflect compensatory adaptations to increased chiasmic decussation, foveal hypoplasia and nystagmus. Hum Brain Mapp 38:740-752, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

THE SMALL BUT SIGNIFICANT AND NONTRANSITORY INCREASE IN PRICES (SSNIP TEST

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Liviana Niminet

2008-12-01

Full Text Available The Small but Significant Nontransitory Increase in Price Test was designed to define the relevant market by concepts of product, geographical area and time. This test, also called the ,,hypothetical monopolistic test” is the subject of many researches both economical and legal as it deals with economic concepts as well as with legally aspects.

Effects of acupuncture on tissue oxygenation of the rat brain.

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Chen, G S; Erdmann, W

1978-04-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by smypathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture points (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible and was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase in inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes increased brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients.

Incidence of Leukoencephalopathy After Whole-Brain Radiation Therapy for Brain Metastases

International Nuclear Information System (INIS)

Ebi, Junko; Sato, Hisashi; Nakajima, Masaru; Shishido, Fumio

2013-01-01

Purpose: To evaluate the incidence of leukoencephalopathy after whole-brain radiation therapy (WBRT) in patients with brain metastases. Methods and Materials: We retrospectively reviewed 111 patients who underwent WBRT for brain metastases from April 2001 through March 2008 and had evaluable computed tomography (CT) and/or magnetic resonance imaging (MRI) at least 1 month after completion of WBRT. We evaluated the leukoencephalopathy according to the Common Terminology Criteria for Adverse Events, version 3.0. The patients who had brain tumor recurrence after WBRT were censored at the last follow-up CT or MRI without recurrence. To evaluate the risk factors for leukoencephalopathy, bivariate analysis was performed using a logistic regression analysis adjusted for follow-up time. Factors included in the analysis were age, gender, dose fractionation, 5-fluorouracil, methotrexate, cisplatin, and other chemotherapeutic agents. Results: The median age of the 111 patients was 60.0 years (range, 23-89 years). The median follow-up was 3.8 months (range, 1.0-38.1 months). Leukoencephalopathy developed in 23 of the 111 patients. Grades 1, 2, and 3 were observed in 8, 7, and 8 patients, respectively. The incidence was 34.4% (11 of 32), 42.9% (6 of 14), 66.7% (2 of 3), and 100% (2 of 2) of the patients who were followed up for ≥6, ≥12, ≥24, and ≥36 months, respectively. In the bivariate analysis, older age (≥65 years) was significantly correlated with higher risk of leukoencephalopathy (odds ratio 3.31; 95% confidence interval 1.15-9.50; P=.03). Conclusions: The incidence of leukoencephalopathy after WBRT was 34.4% with ≥6 months follow-up, and increased with longer follow-up. Older age was a significant risk factor. The schedule of WBRT for patients with brain metastases should be carefully determined, especially for favorable patients

Clinical significance and correlation of the level change of plasma lysophosphatidic acid in patients before and during radiotherapy

International Nuclear Information System (INIS)

Yu Liang; Li Hong; Zhu Shengjie

2011-01-01

Objective: To investigate the effects of radiotherapy on the level of lysophosphatidic acid (LPA) in different patients. Methods: Three groups of patients (metastatic brain tumor group, non-brain tumor group and primary brain tumor group) were given external irradiation (by linear accelerator). LPA level, white blood cell count and platelet count in the blood plasma were evaluated pre-irradiation and after irradiation with 40 Gy and 60 Gy respectively. Results: The LPA level decreased gradually as irradiation doses increase in metastatic brain tumor group non-brain tumor group (after irradiation with 60 Gy 0.05), and neoplasm volume changed little. White blood cell count and platelet count gradually decreased with the increasing irradiation doses in metastatic brain tumor group and primary brain tumor group, but there was no significant correlation to LPA level. However, there was a negative correlation to LPA level in non-brain tumor group (r=-0.285 and r=-0.237, both P<0.05 ). Conclusions: There is a negative correlation between radiotherapy dose and LPA level in metastatic brain tumor patients and non-brain tumor patients. LPA level could be used as a predictor of the effect of the radiotherapy in tumor treatment. (authors)

Mindboggle: Automated brain labeling with multiple atlases

International Nuclear Information System (INIS)

Klein, Arno; Mensh, Brett; Ghosh, Satrajit; Tourville, Jason; Hirsch, Joy

2005-01-01

To make inferences about brain structures or activity across multiple individuals, one first needs to determine the structural correspondences across their image data. We have recently developed Mindboggle as a fully automated, feature-matching approach to assign anatomical labels to cortical structures and activity in human brain MRI data. Label assignment is based on structural correspondences between labeled atlases and unlabeled image data, where an atlas consists of a set of labels manually assigned to a single brain image. In the present work, we study the influence of using variable numbers of individual atlases to nonlinearly label human brain image data. Each brain image voxel of each of 20 human subjects is assigned a label by each of the remaining 19 atlases using Mindboggle. The most common label is selected and is given a confidence rating based on the number of atlases that assigned that label. The automatically assigned labels for each subject brain are compared with the manual labels for that subject (its atlas). Unlike recent approaches that transform subject data to a labeled, probabilistic atlas space (constructed from a database of atlases), Mindboggle labels a subject by each atlas in a database independently. When Mindboggle labels a human subject's brain image with at least four atlases, the resulting label agreement with coregistered manual labels is significantly higher than when only a single atlas is used. Different numbers of atlases provide significantly higher label agreements for individual brain regions. Increasing the number of reference brains used to automatically label a human subject brain improves labeling accuracy with respect to manually assigned labels. Mindboggle software can provide confidence measures for labels based on probabilistic assignment of labels and could be applied to large databases of brain images

Brain atrophy and dementia from the aspect of CT

International Nuclear Information System (INIS)

Ohkuni, Michiko

1979-01-01

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

Increased frequency of retinopathy of prematurity over the last decade and significant regional differences.

Science.gov (United States)

Holmström, Gerd; Tornqvist, Kristina; Al-Hawasi, Abbas; Nilsson, Åsa; Wallin, Agneta; Hellström, Ann

2018-03-01

Retinopathy of prematurity (ROP) causes childhood blindness globally in prematurely born infants. Although increased levels of oxygen supply lead to increased survival and reduced frequency of cerebral palsy, increased incidence of ROP is reported. With the help of a Swedish register for ROP, SWEDROP, national and regional incidences of ROP and frequencies of treatment were evaluated from 2008 to 2015 (n = 5734), as well as before and after targets of provided oxygen changed from 85-89% to 91-95% in 2014. Retinopathy of prematurity (ROP) was found in 31.9% (1829/5734) of all infants with a gestational age (GA) of <31 weeks at birth and 5.7% of the infants (329/5734) had been treated for ROP. Analyses of the national data revealed an increased incidence of ROP during the 8-year study period (p = 0.003), but there was no significant increase in the frequency of treatment. There were significant differences between the seven health regions of Sweden, regarding both incidence of ROP and frequency of treatment (p < 0.001). Comparison of regional data before and after the new oxygen targets revealed a significant increase in treated ROP in one region [OR: 2.24 (CI: 1.11-4.49), p = 0.024] and a borderline increase in one other [OR: 3.08 (CI: 0.99-9.60), p = 0.052]. The Swedish national ROP register revealed an increased incidence of ROP during an 8-year period and significant regional differences regarding the incidence of ROP and frequency of treatment. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Review on herbal medicine on brain ischemia and reperfusion简

Institute of Scientific and Technical Information of China (English)

Nahid; Jivad; Zahra; Rabiei

2015-01-01

Brain ischemia and reperfusion is the leading cause of serious and long-range disability in the world. Clinically significant changes in central nervous system function are observed following brain ischemia and reperfusion. Stroke patients exhibit behavioral, cognitive,emotional, affective and electrophysiological changes during recovery phase. Brain injury by transient complete global brain ischemia or by transient incomplete brain ischemia afflicts a very large number of patients in the world with death or permanent disability. In order to reduce this damage, we must sufficiently understand the mechanisms involved in brain ischemia and reperfusion and repair to design clinically effective therapy.Cerebral ischemia and reperfusion is known to induce the generation of reactive oxygen species that can lead to oxidative damage of proteins, membrane lipids and nucleic acids.A decrease in tissue antioxidant capacity, an increase in lipid peroxidation as well as an increase in lipid peroxidation inhibitors have been demonstrated in several models of brain ischemia. This paper reviews the number of commonly used types of herbal medicines effective for the treatment of stroke. The aim of this paper was to review evidences from controlled studies in order to discuss whether herbal medicine can be helpful in the treatment of brain ischemia and reperfusion.

Altered Brain Excitability and Increased Anxiety in Mice With Experimental Colitis: Consideration of Hyperalgesia and Sex Differences

Directory of Open Access Journals (Sweden)

Kewir D. Nyuyki

2018-04-01

Full Text Available Crohn’s disease (CD and ulcerative colitis (UC are incurable lifelong inflammatory bowel diseases (IBD with a rising worldwide incidence. IBD is characterized by diarrhea, rectal bleeding, severe cramping and weight loss. However, there is a growing evidence that IBD is also associated with anxiety- and depression-related disorders, which further increase the societal burden of these diseases. Given the limited knowledge of central nervous system (CNS changes in IBD, we investigated CNS-related comorbidities in a mouse model of experimental colitis induced by dextran sulfate sodium (DSS administration in drinking water for 5 days. In male and female C57BL6J mice, DSS treatment caused increased brain excitability, revealed by a decrease in seizure onset times after intraperitoneal administration of kainic acid. Moreover, both sexes showed increased anxiety-related behavior in the elevated plus-maze (EPM and open field (OF paradigms. We assessed somatic pain levels, because they may influence behavioral responses. Only male mice were hyperalgesic when tested with calibrated von Frey hairs and on the hotplate for mechanical and thermal pain sensitivity respectively. Administration of diazepam (DZP; ip, 1 mg/kg 30 min before EPM rescued the anxious phenotype and improved locomotion, even though it significantly increased thermal sensitivity in both sexes. This indicates that the altered behavioral response is unlikely attributable to an interference with movement due to somatic pain in females. We show that experimental colitis increases CNS excitability in response to administration of kainic acid, and increases anxiety-related behavior as revealed using the EPM and OF tests.

Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context.

Science.gov (United States)

Alonso, Joan F; Romero, Sergio; Mañanas, Miguel A; Alcalá, Marta; Antonijoan, Rosa M; Giménez, Sandra

2016-04-14

Sleep deprivation (SD) has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE). Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships.

Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context

Directory of Open Access Journals (Sweden)

Joan F. Alonso

2016-04-01

Full Text Available Sleep deprivation (SD has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE. Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships.

Dexamethasone Treatment Reverses Cognitive Impairment but Increases Brain Oxidative Stress in Rats Submitted to Pneumococcal Meningitis

Directory of Open Access Journals (Sweden)

Tatiana Barichello

2011-01-01

Full Text Available Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10 μL of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and cortex. In the step-down inhibitory avoidance task, we observed memory impairment in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The lipid peroxidation was increased in hippocampus in the meningitis groups with dexamethasone and in cortex only in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The protein carbonyl was increased in hippocampus in the meningitis groups with dexamethasone and in cortex in the meningitis groups with and without dexamethasone. There was a decrease in the proteins integrity in hippocampus in all groups receiving treatment with dexamethasone and in cortex in all groups with dexamethasone (0.7 mg/kg/1 day. The mitochondrial superoxide was increased in the hippocampus and cortex in the meningitis group with dexamethasone 0.2 mg/kg/7 days. Our findings demonstrate that dexamethasone reverted cognitive impairment but increased brain oxidative stress in hippocampus and cortex in Wistar rats ten days after pneumococcal meningitis induction.

Brain anatomical networks in early human brain development.

Science.gov (United States)

Fan, Yong; Shi, Feng; Smith, Jeffrey Keith; Lin, Weili; Gilmore, John H; Shen, Dinggang

2011-02-01

Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1 month, 1 year, and 2 years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1 year and 2 years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information. Copyright © 2010. Published by Elsevier Inc.

Age-related decline in cerebral blood flow and brain atrophy

International Nuclear Information System (INIS)

Takeda, Shumpei; Matsuzawa, Taiju; Yamada, Kenji

1987-01-01

Using computed tomography, the authors studied brain atrophy during aging in 536 men and 529 women with no neurologic disturbances. They measured cerebrospinal fluid (CSF) space volume and cranial cavity volume above the level of the tentorium cerebelli and calculated a brain atrophy index. CFS space volume strated to increase significantly in the group aged from 45 to 54 years, while the BAI started to increase significantly in the group aged from 35 to 44 years in both men and women. The BAI increased exponentially with the increasing age after 25 years, continuing to increase until 75 years or more in both men and women: log BAI = -0.260 + 0.0150 x age, r = 0.707, n = 493, p < 0.001 in men; log BAI = -0.434 + 0.0162 x age, r = 0.757, n = 504, p < 0.001 in women. Using the xenon-133 inhalation method, the authors studied age-related decline in regional cerebral blood flow (regional initial slope index; rISI) in 197 men and 238 women with no neurologic disturbances, ranging in age from 19 to 88 years. The rISI values in women declined almost linearly with the advancing age from the 50s to the 80s except the 70s. The rISI values in men declined with the advancing age from the 40s to the 60s, but remained unchanged thereafter until the 80s, suggesting the existence of a threshold of rISI values. We estimated the rISI values (probable threshold of brain atrophy), the frequency under which is equivalent to the volume of brain tissues atrophying in a decade, and obtained constant values as about 32 for men and about 37 for women in the 50s, 60s and 70s. If the frequency of rISI values in the brain is distributed according to a Gaussian function and mean of rISI values decreases linearly to the increasing age, then brain tissues having rISI values below the thresholds degenerate almost exponentially with the increasing age, leading to the exponential atrophy of the brain. (J.P.N.)

BRAIN NETWORKS. Correlated gene expression supports synchronous activity in brain networks.

Science.gov (United States)

Richiardi, Jonas; Altmann, Andre; Milazzo, Anna-Clare; Chang, Catie; Chakravarty, M Mallar; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Lemaître, Hervé; Mann, Karl F; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomáš; Pausova, Zdenka; Rietschel, Marcella; Robbins, Trevor W; Smolka, Michael N; Spanagel, Rainer; Ströhle, Andreas; Schumann, Gunter; Hawrylycz, Mike; Poline, Jean-Baptiste; Greicius, Michael D

2015-06-12

During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function. Copyright © 2015, American Association for the Advancement of Science.

Increased serum brain-derived neurotrophic factor (BDNF) levels in patients with narcolepsy

DEFF Research Database (Denmark)

Klein, Anders B; Jennum, Poul; Knudsen, Stine

2013-01-01

in hypocretin neurons in hypothalamus in post-mortem tissue. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are important for activity-dependent neuronal function and synaptic modulation and it is considered that these mechanisms are important in sleep regulation. We hypothesised......Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction...... that serum levels of these factors are altered in patients with narcolepsy compared to healthy controls without sleep disturbances. Polysomnography data was obtained and serum BDNF and NGF levels measured using ELISA, while hypocretin was measured using RIA. Serum BDNF levels were significantly higher...

Evaluation of Significance of Diffusely Increased Bilateral Renal Uptake on Bone Scan

International Nuclear Information System (INIS)

Sung, Mi Sook; Yang, Woo Jin; Byun, Jae Young; Park, Jung Mi; Shinn, Kyung Sub; Bahk, Yong Whee

1990-01-01

Unexpected renal abnormality can be detected on bone scan using 99m Tc-MDP. The purpose of the study is to evaluate the diagnostic significance of diffusely increased bilateral renal uptake on bone scan. 1,500 bone scan were reviewed and 43 scans which showed diffusely increased bilateral renal uptake were selected for analysis. Laboratory findings for renal and liver function tests including routine urinalysis were reviewed in 43 patients. 26 of 43 case showed abnormality in urinalysis and renal function study. 20 of 43 cases showed abnormal liver function study and 3 of these cases were diagnosed as hepatorenal syndrome later. 13 of those 20 cases had liver cirrhosis with or without hepatoma. 12 of 43 cases showed abnormality both in renal and liver function studies. 2 of 43 cases showed diffusely increased bilateral renal uptake after chemotherapy for cancer but not on previous scans before chemotherapy. 2 of 43 cases showed hypercalcaemia and 8 of 43 cases had multifocal bone uptake due to metastasis or benign bone lesion. But the latter showed no hypercalcaemia at all. There was no significant correlation between increased renal uptake and MDP uptake in soft tissue other than kidneys. This study raised the possibility that the impaired liver and/or renal function may result in diffuse increase of bilateral renal uptake of MDP of unknown mechanism. It seems to need further study on this correlation.

Evaluation of Significance of Diffusely Increased Bilateral Renal Uptake on Bone Scan

Energy Technology Data Exchange (ETDEWEB)

Sung, Mi Sook; Yang, Woo Jin; Byun, Jae Young; Park, Jung Mi; Shinn, Kyung Sub; Bahk, Yong Whee [Catholic University College of Medicine, Seoul (Korea, Republic of)

1990-03-15

Unexpected renal abnormality can be detected on bone scan using {sup 99m}Tc-MDP. The purpose of the study is to evaluate the diagnostic significance of diffusely increased bilateral renal uptake on bone scan. 1,500 bone scan were reviewed and 43 scans which showed diffusely increased bilateral renal uptake were selected for analysis. Laboratory findings for renal and liver function tests including routine urinalysis were reviewed in 43 patients. 26 of 43 case showed abnormality in urinalysis and renal function study. 20 of 43 cases showed abnormal liver function study and 3 of these cases were diagnosed as hepatorenal syndrome later. 13 of those 20 cases had liver cirrhosis with or without hepatoma. 12 of 43 cases showed abnormality both in renal and liver function studies. 2 of 43 cases showed diffusely increased bilateral renal uptake after chemotherapy for cancer but not on previous scans before chemotherapy. 2 of 43 cases showed hypercalcaemia and 8 of 43 cases had multifocal bone uptake due to metastasis or benign bone lesion. But the latter showed no hypercalcaemia at all. There was no significant correlation between increased renal uptake and MDP uptake in soft tissue other than kidneys. This study raised the possibility that the impaired liver and/or renal function may result in diffuse increase of bilateral renal uptake of MDP of unknown mechanism. It seems to need further study on this correlation.

St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

International Nuclear Information System (INIS)

Yang, Shih-Ying; Juang, Shin-Hun; Tsai, Shang-Yuan; Chao, Pei-Dawn Lee; Hou, Yu-Chi

2012-01-01

St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC 0−t and C max of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC 0−t of MTX by 55%. In addition, diclofenac enhanced the C max of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC 0−t and C max of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.

Functional Magnetic Resonance Study of Non-conventional Morphological Brains: malnourished rats

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Martin R.

2015-08-01

Full Text Available Malnutrition during brain development can cause serious problems that can be irreversible. Dysfunctional patterns of brain activity can be detected with functional MRI. We used BOLD functional Magnetic Resonance Imaging (fMRI to investigate region differences of brain activity between control and malnourished rats. The food-competition method was applied to a rat model to induce malnutrition during lactation. A 7T magnet was used to detect changes of the BOLD signal associated with changes in brain activity caused by the trigeminal nerve stimulation in malnourished and control rats. Major neuronal activation was observed in malnourished rats in several brain regions, including cerebellum, somatosensory cortex, hippocampus, and hypothalamus. Statistical analysis of the BOLD signals from various brain areas revealed significant differences in somatosensory cortex between the control and experimental groups, as well as a significant difference between the cerebellum and other structures in the experimental group. This study, particularly in malnourished rats, demonstrates increased BOLD activation in the cerebellum.

Effects of acupuncture on tissue-oxygenation of the rat brain.

Science.gov (United States)

Chen, G S; Erdmann, W

1977-01-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by sympathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex of the animals through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture loci (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible. The effect was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase of inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes an increase of brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients. Dilatation of cerebral vascular vessels and improvement of autoregulation in the brain by acupuncture stimulation may also explain the effectiveness of acupuncture in the treatment of migraine headache.

The Eye/Brain Radioactivity Ratio for Assessment of Graves Ophthalmopathy

International Nuclear Information System (INIS)

Lee, B. W.; Sung, S. K.; Suh, K. S.; Park, W.; Choi, D. J.; Kim, J. S.

1988-01-01

In Graves' disease, changes in orbital tissue and structure are caused by inflammatory infiltration, which induces increase of capillary permeability and breakdown of blood-tissue barriers. Using the uptake of 99m Tc-DTPA in inflammatory lesion, Eye/Brain radioactivity ratios in brain scintigraphy were evaluated in 15 normal controls and 40 Graves' patients. The results were as follows; 1) Eye/Brain radioactivity ratio was significantly higher in Graves' ophthalmopathy group than in control group (p 99m Tc-DTPA brain scintigraphy may be useful to determine the activity of Graves' ophthalmopathy and whether treatment of Graves' ophthalmopathy is necessary or not.

Early monitoring of PtiO2, PtiCO2, pH and brain temperat ure in patients with brain injuries and the clinical significanc e

Institute of Scientific and Technical Information of China (English)

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