WorldWideScience

Sample records for showed decreased brain

  1. Decreased anxiety- and depression-like behaviors and hyperactivity in a type 3 deiodinase-deficient mouse showing brain thyrotoxicosis and peripheral hypothyroidism.

    Science.gov (United States)

    Stohn, J Patrizia; Martinez, M Elena; Hernandez, Arturo

    2016-12-01

    Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 -/- mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 -/- mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 -/- mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Low doses of alcohol substantially decrease glucose metabolism in the human brain.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Franceschi, Dinko; Fowler, Joanna S; Thanos, Panayotis Peter K; Maynard, Laurence; Gatley, S John; Wong, Christopher; Veech, Richard L; Kunos, George; Kai Li, Ting

    2006-01-01

    Moderate doses of alcohol decrease glucose metabolism in the human brain, which has been interpreted to reflect alcohol-induced decreases in brain activity. Here, we measure the effects of two relatively low doses of alcohol (0.25 g/kg and 0.5 g/kg, or 5 to 10 mM in total body H2O) on glucose metabolism in the human brain. Twenty healthy control subjects were tested using positron emission tomography (PET) and FDG after placebo and after acute oral administration of either 0.25 g/kg, or 0.5 g/kg of alcohol, administered over 40 min. Both doses of alcohol significantly decreased whole-brain glucose metabolism (10% and 23% respectively). The responses differed between doses; whereas the 0.25 g/kg dose predominantly reduced metabolism in cortical regions, the 0.5 g/kg dose reduced metabolism in cortical as well as subcortical regions (i.e. cerebellum, mesencephalon, basal ganglia and thalamus). These doses of alcohol did not significantly change the scores in cognitive performance, which contrasts with our previous results showing that a 13% reduction in brain metabolism by lorazepam was associated with significant impairment in performance on the same battery of cognitive tests. This seemingly paradoxical finding raises the possibility that the large brain metabolic decrements during alcohol intoxication could reflect a shift in the substrate for energy utilization, particularly in light of new evidence that blood-borne acetate, which is markedly increased during intoxication, is a substrate for energy production by the brain.

  3. Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6

    DEFF Research Database (Denmark)

    Molinero, Amalia; Penkowa, Milena; Hernández, Joaquín

    2003-01-01

    in this report support the idea that the upregulation of MT-I observed in GFAP-IL6 mice is an important mechanism for coping with brain damage. Thus, GFAP-IL6 mice that were crossed with TgMTI transgenic mice (GFAP-IL6xTgMTI) and overexpressed MT-I in the brain showed a decreased upregulation of cytokines...... such as IL-6 and a diminished recruitment and activation of macrophages and T cells throughout the CNS but mainly in the cerebellum. The GFAP-IL6 mice showed clear evidence of increased oxidative stress, which was significantly decreased by MT-I overexpression. Interestingly, MT-I overexpression increased...

  4. Bipolar I disorder and major depressive disorder show similar brain activation during depression.

    Science.gov (United States)

    Cerullo, Michael A; Eliassen, James C; Smith, Christopher T; Fleck, David E; Nelson, Erik B; Strawn, Jeffrey R; Lamy, Martine; DelBello, Melissa P; Adler, Caleb M; Strakowski, Stephen M

    2014-11-01

    Despite different treatments and courses of illness, depressive symptoms appear similar in major depressive disorder (MDD) and bipolar I disorder (BP-I). This similarity of depressive symptoms suggests significant overlap in brain pathways underlying neurovegetative, mood, and cognitive symptoms of depression. These shared brain regions might be expected to exhibit similar activation in individuals with MDD and BP-I during functional magnetic resonance imaging (fMRI). fMRI was used to compare regional brain activation in participants with BP-I (n = 25) and MDD (n = 25) during a depressive episode as well as 25 healthy comparison (HC) participants. During the scans, participants performed an attentional task that incorporated emotional pictures. During the viewing of emotional images, subjects with BP-I showed decreased activation in the middle occipital gyrus, lingual gyrus, and middle temporal gyrus compared to both subjects with MDD and HC participants. During attentional processing, participants with MDD had increased activation in the parahippocampus, parietal lobe, and postcentral gyrus. However, among these regions, only the postcentral gyrus also showed differences between MDD and HC participants. No differences in cortico-limbic regions were found between participants with BP-I and MDD during depression. Instead, the major differences occurred in primary and secondary visual processing regions, with decreased activation in these regions in BP-I compared to major depression. These differences were driven by abnormal decreases in activation seen in the participants with BP-I. Posterior activation changes are a common finding in studies across mood states in participants with BP-I. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Ammonia causes decreased brain monoamines in fathead minnows (Pimephales promelas)

    Science.gov (United States)

    Ronan, Patrick J.; Gaikowski, Mark P.; Hamilton, Steven J.; Buhl, Kevin J.; Summers, Cliff H.

    2007-01-01

    Hyperammonemia, arising from variety of disorders, leads to severe neurological dysfunction. The mechanisms of ammonia toxicity in brain are not completely understood. This study investigated the effects of ammonia on monoaminergic systems in brains of fathead minnows (Pimephales promelas). Fish serve as a good model system to investigate hyperammonemic effects on brain function since no liver manipulations are necessary to increase endogenous ammonia concentrations. Using high performance liquid chromatography with electrochemical detection, monoamines and some associated metabolites were measured from whole brain homogenate. Adult males were exposed for 48 h to six different concentrations of ammonia (0.01–2.36 mg/l unionized) which bracketed the 96-h LC50 for this species. Ammonia concentration-dependent decreases were found for the catecholamines (norepinephrine and dopamine) and the indoleamine serotonin (5-HT). After an initial increase in the 5-HT precursor 5-hydroxytryptophan it too decreased with increasing ammonia concentrations. There were also significant increases in the 5-HIAA/5-HT and DOPAC/DA ratios, often used as measures of turnover. There were no changes in epinephrine (Epi) or monoamine catabolites (DOPAC, 5-HIAA) at any ammonia concentrations tested. Results suggest that ammonia causes decreased synthesis while also causing increased release and degradation. Increased release may underlie behavioral reactions to ammonia exposure in fish. This study adds weight to a growing body of evidence demonstrating that ammonia leads to dysfunctional monoaminergic systems in brain which may underlie neurological symptoms associated with human disorders such as hepatic encephalopathy.

  6. Rats with decreased brain cholecystokinin levels show increased responsiveness to peripheral electrical stimulation-induced analgesia.

    Science.gov (United States)

    Zhang, L X; Li, X L; Wang, L; Han, J S

    1997-01-16

    Using the P77PMC strain of rat, which is genetically prone to audiogenic seizures, and also has decreased levels of cholecystokinin (CCK), we examined the analgesic response to peripheral electrical stimulation, which is, in part, opiate-mediated. A number of studies have suggested that CCK may function as an antagonist to endogenous opiate effects. Therefore, we hypothesized that the P77PMC animals would show an enhanced analgesic response based on their decreased CCK levels producing a diminished endogenous opiate antagonism. We found that the analgesic effect on tail flick latency produced by 100 Hz peripheral electrical stimulation was more potent and longer lasting in P77PMC rats than in control rats. Moreover, the potency of the stimulation-produced analgesia correlated with the vulnerability to audiogenic seizures in these rats. We were able to block the peripheral electrical stimulation-induced analgesia (PSIA) using a cholecystokinin octapeptide (CCK-8) administered parenterally. Radioimmunoassay showed that the content of CCK-8 in cerebral cortex, hippocampus and periaqueductal gray was much lower in P77PMC rat than in controls. These results suggest that low CCK-8 content in the central nervous system of the P77PMC rats may be related to the high analgesic response to peripheral electrical stimulation, and further support the notion that CCK may be endogenous opiate antagonist.

  7. Olfactory Dysfunctions and Decreased Nitric Oxide Production in the Brain of Human P301L Tau Transgenic Mice.

    Science.gov (United States)

    Hu, Yang; Ding, Wenting; Zhu, Xiaonan; Chen, Ruzhu; Wang, Xuelan

    2016-04-01

    Different patterns of olfactory dysfunction have been found in both patients and mouse models of Alzheimer's Disease. However, the underlying mechanism of the dysfunction remained unknown. Deficits of nitric oxide production in brain can cause olfactory dysfunction by preventing the formation of olfactory memory. The aim of this study was to investigate the behavioral changes in olfaction and alterations in metabolites of nitric oxide, nitrate/nitrite concentration, in the brain of human P301L tau transgenic mice. The tau mice showed impairments in olfaction and increased abnormal phosphorylation of Tau protein at AT8 in different brain areas, especially in olfactory bulb. We now report that these olfactory deficits and Tau pathological changes were accompanied by decreased nitrate/nitrite concentration in the brain, especially in the olfactory bulb, and reduced expression of nNOS in the brain of tau mice. These findings provided evidence of olfactory dysfunctions correlated with decreased nitric oxide production in the brain of tau mice.

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  9. Increased Arousal Levels and Decreased Sleep by Brain Music in Rats

    Institute of Scientific and Technical Information of China (English)

    Guang-Zhan Fang; Chun-Peng Zhang; Dan Wu; Yang Xia; Yong-Xiu Lai; De-Zhong Yao

    2009-01-01

    More and more studies have been reported on whether music and other types of auditory stimulation would improve the quality of sleep.Many of these studies have found significant results,but others argue that music is not significantly better than the tones or control conditions in improving sleep.For further understanding the relationship between music and sleep or music and arousal,the present study therefore examines the effects of brain music on sleep and arousal by means of biofeedback.The music is from the transformation of rapid eye movement (REM) sleep electroencephalogram (EEG) of rats using an algorithm in the Chengdu Brain Music (CBM) system.When the brain music was played back to rats,EEG data were recorded to assess the efficacy of music to induce or improve sleep,or increase arousal levels by sleep staging,etc.Our results demonstrate that exposure to the brain music increases arousal levels and decreases sleep in rats,and the underlying mechanism of decreased non-rapid eye movement (NREM) and REM sleep may be different.

  10. Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice

    Science.gov (United States)

    Lin, Ai-Ling; Pulliam, Daniel A; Deepa, Sathyaseelan S; Halloran, Jonathan J; Hussong, Stacy A; Burbank, Raquel R; Bresnen, Andrew; Liu, Yuhong; Podlutskaya, Natalia; Soundararajan, Anuradha; Muir, Eric; Duong, Timothy Q; Bokov, Alex F; Viscomi, Carlo; Zeviani, Massimo; Richardson, Arlan G; Van Remmen, Holly; Fox, Peter T; Galvan, Veronica

    2013-01-01

    Recent studies have challenged the prevailing view that reduced mitochondrial function and increased oxidative stress are correlated with reduced longevity. Mice carrying a homozygous knockout (KO) of the Surf1 gene showed a significant decrease in mitochondrial electron transport chain Complex IV activity, yet displayed increased lifespan and reduced brain damage after excitotoxic insults. In the present study, we examined brain metabolism, brain hemodynamics, and memory of Surf1 KO mice using in vitro measures of mitochondrial function, in vivo neuroimaging, and behavioral testing. We show that decreased respiration and increased generation of hydrogen peroxide in isolated Surf1 KO brain mitochondria are associated with increased brain glucose metabolism, cerebral blood flow, and lactate levels, and with enhanced memory in Surf1 KO mice. These metabolic and functional changes in Surf1 KO brains were accompanied by higher levels of hypoxia-inducible factor 1 alpha, and by increases in the activated form of cyclic AMP response element-binding factor, which is integral to memory formation. These findings suggest that Surf1 deficiency-induced metabolic alterations may have positive effects on brain function. Exploring the relationship between mitochondrial activity, oxidative stress, and brain function will enhance our understanding of cognitive aging and of age-related neurologic disorders. PMID:23838831

  11. Decreased integration and information capacity in stroke measured by whole brain models of resting state activity.

    Science.gov (United States)

    Adhikari, Mohit H; Hacker, Carl D; Siegel, Josh S; Griffa, Alessandra; Hagmann, Patric; Deco, Gustavo; Corbetta, Maurizio

    2017-04-01

    While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to

  12. Psychoacoustic Tinnitus Loudness and Tinnitus-Related Distress Show Different Associations with Oscillatory Brain Activity

    Science.gov (United States)

    Balkenhol, Tobias; Wallhäusser-Franke, Elisabeth; Delb, Wolfgang

    2013-01-01

    Background The phantom auditory perception of subjective tinnitus is associated with aberrant brain activity as evidenced by magneto- and electroencephalographic studies. We tested the hypotheses (1) that psychoacoustically measured tinnitus loudness is related to gamma oscillatory band power, and (2) that tinnitus loudness and tinnitus-related distress are related to distinct brain activity patterns as suggested by the distinction between loudness and distress experienced by tinnitus patients. Furthermore, we explored (3) how hearing impairment, minimum masking level, and (4) psychological comorbidities are related to spontaneous oscillatory brain activity in tinnitus patients. Methods and Findings Resting state oscillatory brain activity recorded electroencephalographically from 46 male tinnitus patients showed a positive correlation between gamma band oscillations and psychoacoustic tinnitus loudness determined with the reconstructed tinnitus sound, but not with the other psychoacoustic loudness measures that were used. Tinnitus-related distress did also correlate with delta band activity, but at electrode positions different from those associated with tinnitus loudness. Furthermore, highly distressed tinnitus patients exhibited a higher level of theta band activity. Moreover, mean hearing loss between 0.125 kHz and 16 kHz was associated with a decrease in gamma activity, whereas minimum masking levels correlated positively with delta band power. In contrast, psychological comorbidities did not express significant correlations with oscillatory brain activity. Conclusion Different clinically relevant tinnitus characteristics show distinctive associations with spontaneous brain oscillatory power. Results support hypothesis (1), but exclusively for the tinnitus loudness derived from matching to the reconstructed tinnitus sound. This suggests to preferably use the reconstructed tinnitus spectrum to determine psychoacoustic tinnitus loudness. Results also support

  13. Structural imaging of the brain reveals decreased total brain and total gray matter volumes in obese but not in lean women with polycystic ovary syndrome compared to body mass index-matched counterparts.

    Science.gov (United States)

    Ozgen Saydam, Basak; Has, Arzu Ceylan; Bozdag, Gurkan; Oguz, Kader Karli; Yildiz, Bulent Okan

    2017-07-01

    To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls. Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed. Total brain volume and total gray matter volume (GMV) were decreased in obese PCOS compared to obese controls (p lean PCOS and controls did not show a significant difference. Secondary analyses of regional brain volumes showed decreases in GMV of the caudate nucleus, ventral diencephalon and hippocampus in obese PCOS compared to obese controls (p lean patients with PCOS had lower GMV in the amygdala than lean controls (p PCOS, suggests volumetric reductions in global brain areas in obese women with PCOS. Functional studies with larger sample size are needed to determine physiopathological roles of these changes and potential effects of long-term medical management on brain structure of PCOS.

  14. Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission.

    Science.gov (United States)

    Ragnarsson, Oskar; Stomby, Andreas; Dahlqvist, Per; Evang, Johan A; Ryberg, Mats; Olsson, Tommy; Bollerslev, Jens; Nyberg, Lars; Johannsson, Gudmundur

    2017-08-01

    Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 controls matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working-memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (pright inferior occipital gyrus (pbrain responses in the left posterior hippocampus in patients (p=0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (pbrain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. 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.

  18. Chronic sucrose intake decreases concentrations of n6 fatty acids, but not docosahexaenoic acid in the rat brain phospholipids.

    Science.gov (United States)

    Mašek, Tomislav; Starčević, Kristina

    2017-07-13

    We investigated the influence of high sucrose intake, administered in drinking water, on the lipid profile of the brain and on the expression of SREBP1c and Δ-desaturase genes. Adult male rats received 30% sucrose solution for 20 weeks (Sucrose group), or plain water (Control group). After the 20th week of sucrose treatment, the Sucrose group showed permanent hyperglycemia. Sucrose treatment also increased the amount of total lipids and fatty acids in the brain. The brain fatty acid profile of total lipids as well as phosphatidylethanolamine, phosphatidylcholine and cardiolipin of the Sucrose group was extensively changed. The most interesting change was a significant decrease in n6 fatty acids, including the important arachidonic acid, whereas the content of oleic and docosahexaenoic acid remained unchanged. RT-qPCR revealed an increase in Δ-5-desaturase and SREBP1c gene expression. In conclusion, high sucrose intake via drinking water extensively changes rat brain fatty acid profile by decreasing n6 fatty acids, including arachidonic acid. In contrast, the content of docosahexaenoic acid remains constant in the brain total lipids as well as in phospholipids. Changes in the brain fatty acid profile reflect changes in the lipid metabolism of the rat lipogenic tissues and concentrations in the circulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Grainyhead-like 3 (Grhl3) deficiency in brain leads to altered locomotor activity and decreased anxiety-like behaviors in aged mice.

    Science.gov (United States)

    Dworkin, Sebastian; Auden, Alana; Partridge, Darren D; Daglas, Maria; Medcalf, Robert L; Mantamadiotis, Theo; Georgy, Smitha R; Darido, Charbel; Jane, Stephen M; Ting, Stephen B

    2017-06-01

    The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation, and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here they show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviors. Using both Grhl3-knockout mice (Grhl3 -/- ), and brain-specific conditional deletion of Grhl3 in adult mice (Nestin-Cre/Grhl3 flox/flox ), they performed histological expression analyses and behavioral tests to assess long-term effects of Grhl3 loss on motor co-ordination, spatial memory, anxiety, and stress. They found that complete deletion of Grhl3 did not lead to noticeable structural or cell-intrinsic defects in the embryonic brain; however, aged Grhl3 conditional knockout (cKO) mice showed enlarged lateral ventricles and displayed marked changes in motor function and behaviors suggestive of decreased fear and anxiety. They conclude that loss of Grhl3 in the brain leads to significant alterations in locomotor activity and decreased self-inhibition, and as such, these mice may serve as a novel model of human conditions of impulsive behavior or hyperactivity. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 775-788, 2017. © 2017 Wiley Periodicals, Inc.

  20. Statistical probabilistic mapping in the individual brain space: decreased metabolism in epilepsy with FDG PET

    International Nuclear Information System (INIS)

    Oh, Jung Su; Lee, Jae Sung; Kim, Yu Kyeong; Chung, June Key; Lee, Myung Chul; Lee, Dong Soo

    2005-01-01

    In the statistical probabilistic mapping, commonly, differences between two or more groups of subjects are statistically analyzed following spatial normalization. However, to our best knowledge, there is few study which performed the statistical mapping in the individual brain space rather than in the stereotaxic brain space, i.e., template space. Therefore, in the current study, a new method for mapping the statistical results in the template space onto individual brain space has been developed. Four young subjects with epilepsy and their age-matched thirty normal healthy subjects were recruited. Both FDG PET and T1 structural MRI was scanned in these groups. Statistical analysis on the decreased FDG metabolism in epilepsy was performed on the SPM with two sample t-test (p < 0.001, intensity threshold 100). To map the statistical results onto individual space, inverse deformation was performed as follows. With SPM deformation toolbox, DCT (discrete cosine transform) basis-encoded deformation fields between individual T1 images and T1 MNI template were obtained. Afterward, inverse of those fields, i.e., inverse deformation fields were obtained. Since both PET and T1 images have been already normalized in the same MNI space, inversely deformed results in PET is on the individual brain MRI space. By applying inverse deformation field on the statistical results of the PET, the statistical map of decreased metabolism in individual spaces were obtained. With statistical results in the template space, localization of decreased metabolism was in the inferior temporal lobe, which was slightly inferior to the hippocampus. The statistical results in the individual space were commonly located in the hippocampus, where the activation should be decreased according to a priori knowledge of neuroscience. With our newly developed statistical mapping on the individual spaces, the localization of the brain functional mapping became more appropriate in the sense of neuroscience

  1. Statistical probabilistic mapping in the individual brain space: decreased metabolism in epilepsy with FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jung Su; Lee, Jae Sung; Kim, Yu Kyeong; Chung, June Key; Lee, Myung Chul; Lee, Dong Soo [Seoul National University Hospital, Seoul (Korea, Republic of)

    2005-07-01

    In the statistical probabilistic mapping, commonly, differences between two or more groups of subjects are statistically analyzed following spatial normalization. However, to our best knowledge, there is few study which performed the statistical mapping in the individual brain space rather than in the stereotaxic brain space, i.e., template space. Therefore, in the current study, a new method for mapping the statistical results in the template space onto individual brain space has been developed. Four young subjects with epilepsy and their age-matched thirty normal healthy subjects were recruited. Both FDG PET and T1 structural MRI was scanned in these groups. Statistical analysis on the decreased FDG metabolism in epilepsy was performed on the SPM with two sample t-test (p < 0.001, intensity threshold 100). To map the statistical results onto individual space, inverse deformation was performed as follows. With SPM deformation toolbox, DCT (discrete cosine transform) basis-encoded deformation fields between individual T1 images and T1 MNI template were obtained. Afterward, inverse of those fields, i.e., inverse deformation fields were obtained. Since both PET and T1 images have been already normalized in the same MNI space, inversely deformed results in PET is on the individual brain MRI space. By applying inverse deformation field on the statistical results of the PET, the statistical map of decreased metabolism in individual spaces were obtained. With statistical results in the template space, localization of decreased metabolism was in the inferior temporal lobe, which was slightly inferior to the hippocampus. The statistical results in the individual space were commonly located in the hippocampus, where the activation should be decreased according to a priori knowledge of neuroscience. With our newly developed statistical mapping on the individual spaces, the localization of the brain functional mapping became more appropriate in the sense of neuroscience.

  2. Decreased weight, DNA, RNA and protein content of the brain after neutron irradiation of the 18-day mouse embryo

    International Nuclear Information System (INIS)

    Antal, S.; Fonagy, A.; Hidvegi, E.J.; Fueloep, Z.; Vogel, H.H. Jr.

    1984-01-01

    Pregnant mice were irradiated with 0.5 Gy fission neutrons on the eighteenth day of gestation. Average litter size at birth was unchanged but mortality increased 5-6 fold in the first 3 days. Irradiated mice were the same weight as control mice at birth but showed a progressively increasing weight deficiency up to at least 36 days compared to controls. Brain weight was 37, 45 and 25% less in 2-, 3- and 52-week old irradiated animals; the ratio of brain weight to body weight was 25, 27 and 13% less. The concentrations of DNA, RNA and protein (mg/g wet tissue) were the same in irradiated and control mice in brain and liver at all three ages. Total DNA, RNA and protein contents of whole brain after irradiation were 56-75% of control levels. No definite decrease was observed in liver. Histological study at 6 hours after irradiation showed nuclear pyknosis in the central nervous system from definite to very severe according to the part examined. It is concluded that damage to the central nervous system of the 18-day mouse foetus is mainly due to killing and/or inhibition of the differentiation of neuroblasts. (author)

  3. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    International Nuclear Information System (INIS)

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-01-01

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET- 18 FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

  4. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

  5. Decreased serum hepcidin concentration correlates with brain iron deposition in patients with HBV-related cirrhosis.

    Directory of Open Access Journals (Sweden)

    Dong Lin

    Full Text Available PURPOSE: Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level. METHODS: Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters. RESULTS: Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients. CONCLUSIONS: Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional

  6. A Stepwise Approach: Decreasing Infection in Deep Brain Stimulation for Childhood Dystonic Cerebral Palsy.

    Science.gov (United States)

    Johans, Stephen J; Swong, Kevin N; Hofler, Ryan C; Anderson, Douglas E

    2017-09-01

    Dystonia is a movement disorder characterized by involuntary muscle contractions, which cause twisting movements or abnormal postures. Deep brain stimulation has been used to improve the quality of life for secondary dystonia caused by cerebral palsy. Despite being a viable treatment option for childhood dystonic cerebral palsy, deep brain stimulation is associated with a high rate of infection in children. The authors present a small series of patients with dystonic cerebral palsy who underwent a stepwise approach for bilateral globus pallidus interna deep brain stimulation placement in order to decrease the rate of infection. Four children with dystonic cerebral palsy who underwent a total of 13 surgical procedures (electrode and battery placement) were identified via a retrospective review. There were zero postoperative infections. Using a multistaged surgical plan for pediatric patients with dystonic cerebral palsy undergoing deep brain stimulation may help to reduce the risk of infection.

  7. Bupropion sustained release treatment decreases craving for video games and cue-induced brain activity in patients with Internet video game addiction.

    Science.gov (United States)

    Han, Doug Hyun; Hwang, Jun Won; Renshaw, Perry F

    2010-08-01

    Bupropion has been used in the treatment of patients with substance dependence based on its weak inhibition of dopamine and norepinephrine reuptake. We hypothesized that 6 weeks of bupropion sustained release (SR) treatment would decrease craving for Internet game play as well as video game cue-induced brain activity in patients with Internet video game addiction (IAG). Eleven subjects who met criteria for IAG, playing StarCraft (>30 hr/week), and eight healthy comparison subjects (HC) who had experience playing StarCraft (game, and the severity of Internet addiction were evaluated by Beck Depression Inventory, self-report of craving on a 7-point visual analogue scale, and Young's Internet Addiction Scale, respectively. In response to game cues, IAG showed higher brain activation in left occipital lobe cuneus, left dorsolateral prefrontal cortex, and left parahippocampal gyrus than HC. After a 6 week period of bupropion SR, craving for Internet video game play, total game play time, and cue-induced brain activity in dorsolateral prefrontal cortex were decreased in the IAG. We suggest that bupropion SR may change craving and brain activity in ways that are similar to those observed in individuals with substance abuse or dependence. PsycINFO Database Record 2010 APA, all rights reserved.

  8. Left and right brain-oriented hemisity subjects show opposite behavioral preferences.

    Science.gov (United States)

    Morton, Bruce E

    2012-01-01

    Recently, three independent, intercorrelated biophysical measures have provided the first quantitative measures of a binary form of behavioral laterality called "Hemisity," a term referring to inherent opposite right or left brain-oriented differences in thinking and behavioral styles. Crucially, the right or left brain-orientation of individuals assessed by these methods was later found to be essentially congruent with the thicker side of their ventral gyrus of the anterior cingulate cortex (vgACC) as revealed by a 3 min MRI procedure. Laterality of this putative executive structural element has thus become the primary standard defining individual hemisity. Here, the behavior of 150 subjects, whose hemisity had been calibrated by MRI, was assessed using five MRI-calibrated preference questionnaires, two of which were new. Right and left brain-oriented subjects selected opposite answers (p > 0.05) for 47 of the 107 "either-or," forced choice type preference questionnaire items. The resulting 30 hemisity subtype preference differences were present in several areas. These were: (1) in logical orientation, (2) in type of consciousness, (3) in fear level and sensitivity, (4) in social-professional orientation, and (5) in pair bonding-spousal dominance style. The right and left brain-oriented hemisity subtype subjects, sorted on the anatomical basis of upon which brain side their vgACC was thickest, showed 30 significant differences in their "either-or" type of behavioral preferences.

  9. Left and right brain-oriented hemisity subjects show opposite behavioral preferences

    Directory of Open Access Journals (Sweden)

    Bruce Eldine Morton

    2012-11-01

    Full Text Available Introduction: Recently, three independent, intercorrelated biophysical measures have provided the first quantitative measures of a binary form of behavioral laterality called Hemisity, a term referring to inherent opposite right or left brain-oriented differences in thinking and behavioral styles. Crucially, the right or left brain-orientation of individuals assessed by these methods was later found to be essentially congruent with the thicker side of their ventral gyrus of the anterior cingulate cortex (vgACC as revealed by a 3 minute MRI procedure. Laterality of this putative executive structural element has thus become the primary standard defining individual hemisity. Methods: Here, the behavior of 150 subjects, whose hemisity had been calibrated by MRI, was assessed using five MRI-calibrated preference questionnaires, two of which were new.Results: Right and left brain-oriented subjects selected opposite answers (p > 0.05 for 47 of the 107 either-or, forced choice type preference questionnaire items. Hemisity subtype preference differences were present in several areas. They were in: a. logical orientation, b. type of consciousness, c. fear level and sensitivity, d. social-professional orientation, and e. pair bonding-spousal dominance style.Conclusions: The right and left brain-oriented hemisity subtype subjects, sorted on the anatomical basis of upon which brain side their vgACC was thickest, showed numerous significant differences in their either-or type of behavioral preferences.

  10. Addiction: Decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain's control circuit

    OpenAIRE

    Volkow, Nora D.; Wang, Gene-Jack; Fowler, Joanna S.; Tomasi, Dardo; Telang, Frank; Baler, Ruben

    2010-01-01

    Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is larg...

  11. Decreased α1-adrenergic receptor-mediated inositide hydrolysis in neurons from hypertensive rat brain

    International Nuclear Information System (INIS)

    Feldstein, J.B.; Gonzales, R.A.; Baker, S.P.; Sumners, C.; Crews, F.T.; Raizada, M.K.

    1986-01-01

    The expression of α 1 -adrenergic receptors and norepinephrine (NE)-stimulated hydrolysis of inositol phospholipid has been studied in neuronal cultures from the brains of normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SH) rats. Binding of 125 I-1-[β-(4-hydroxyphenyl)-ethyl-aminomethyl] tetralone (HEAT) to neuronal membranes was 68-85% specific and was rapid. Competition-inhibition experiments with various agonists and antagonists suggested that 125 I-HEAT bound selectively to α 1 -adrenergic receptors. Specific binding of 125 I-HEAT to neuronal membranes from SH rat brain cultures was 30-45% higher compared with binding in WKY normotensive controls. This increase was attributed to an increase in the number of α 1 -adrenergic receptors on SH rat brain neurons. Incubation of neuronal cultures of rat brain from both strains with NE resulted in a concentration-dependent stimulation of release of inositol phosphates, although neurons from SH rat brains were 40% less responsive compared with WKY controls. The decrease in responsiveness of SH rat brain neurons to NE, even though the α 1 -adrenergic receptors are increased, does not appear to be due to a general defect in membrane receptors and postreceptor signal transduction mechanisms. This is because neither the number of muscarinic-cholinergic receptors nor the carbachol-stimulated release of inositol phosphates is different in neuronal cultures from the brains of SH rats compared with neuronal cultures from the brains of WKY rats. These observations suggest that the increased expression of α 1 -adrenergic receptors does not parallel the receptor-mediated inositol phosphate hydrolysis in neuronal cultures from SH rat brain

  12. Mutation in HFE gene decreases manganese accumulation and oxidative stress in the brain after olfactory manganese exposure.

    Science.gov (United States)

    Ye, Qi; Kim, Jonghan

    2016-06-01

    Increased accumulation of manganese (Mn) in the brain is significantly associated with neurobehavioral deficits and impaired brain function. Airborne Mn has a high systemic bioavailability and can be directly taken up into the brain, making it highly neurotoxic. While Mn transport is in part mediated by several iron transporters, the expression of these transporters is altered by the iron regulatory gene, HFE. Mutations in the HFE gene are the major cause of the iron overload disorder, hereditary hemochromatosis, one of the prevalent genetic diseases in humans. However, whether or not HFE mutation modifies Mn-induced neurotoxicity has not been evaluated. Therefore, our goal was to define the role of HFE mutation in Mn deposition in the brain and the resultant neurotoxic effects after olfactory Mn exposure. Mice carrying the H67D HFE mutation, which is homologous to the H63D mutation in humans, and their control, wild-type mice, were intranasally instilled with MnCl2 with different doses (0, 0.2, 1.0 and 5.0 mg kg(-1)) daily for 3 days. Mn levels in the blood, liver and brain were determined using inductively-coupled plasma mass spectrometry (ICP-MS). H67D mutant mice showed significantly lower Mn levels in the blood, liver, and most brain regions, especially in the striatum, while mice fed an iron-overload diet did not. Moreover, mRNA expression of ferroportin, an essential exporter of iron and Mn, was up-regulated in the striatum. In addition, the levels of isoprostane, a marker of lipid peroxidation, were increased in the striatum after Mn exposure in wild-type mice, but were unchanged in H67D mice. Together, our results suggest that the H67D mutation provides decreased susceptibility to Mn accumulation in the brain and neurotoxicity induced by inhaled Mn.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Prenatal Exposure to Tributyltin Decreases GluR2 Expression in the Mouse Brain.

    Science.gov (United States)

    Ishida, Keishi; Saiki, Takashi; Umeda, Kanae; Miyara, Masatsugu; Sanoh, Seigo; Ohta, Shigeru; Kotake, Yaichiro

    2017-01-01

    Tributyltin (TBT), a common environmental contaminant, is widely used as an antifouling agent in paint. We previously reported that exposure of primary cortical neurons to TBT in vitro decreased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit glutamate receptor 2 (GluR2) expression and subsequently increased neuronal vulnerability to glutamate. Therefore, to identify whether GluR2 expression also decreases after TBT exposure in vivo, we evaluated the changes in GluR2 expression in the mouse brain after prenatal or postnatal exposure to 10 and 25 ppm TBT through pellet diets. Although the mean feed intake and body weight did not decrease in TBT-exposed mice compared with that in control mice, GluR2 expression in the cerebral cortex and hippocampus decreased after TBT exposure during the prenatal period. These results indicate that a decrease in neuronal GluR2 may be involved in TBT-induced neurotoxicity, especially during the fetal period.

  15. Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow.

    Science.gov (United States)

    Linnman, Clas; Catana, Ciprian; Svärdsudd, Kurt; Appel, Lieuwe; Engler, Henry; Långström, Bengt; Sörensen, Jens; Furmark, Tomas; Fredrikson, Mats; Borsook, David; Peterson, Magnus

    Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.

  16. Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow.

    Directory of Open Access Journals (Sweden)

    Clas Linnman

    Full Text Available Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1 receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis were selected out of a larger (n = 120 randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis. These ten subjects were examined by positron emission tomography (PET with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA, was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.

  17. Hemodialysis decreases serum brain-derived neurotrophic factor concentration in humans.

    Science.gov (United States)

    Zoladz, Jerzy A; Śmigielski, Michał; Majerczak, Joanna; Nowak, Łukasz R; Zapart-Bukowska, Justyna; Smoleński, Olgierd; Kulpa, Jan; Duda, Krzysztof; Drzewińska, Joanna; Bartosz, Grzegorz

    2012-12-01

    In the present study we have evaluated the effect of a single hemodialysis session on the brain-derived neurotrophic factor levels in plasma [BDNF](pl) and in serum [BDNF](s) as well as on the plasma isoprostanes concentration [F(2) isoprostanes](pl), plasma total antioxidant capacity (TAC) and plasma cortisol levels in chronic kidney disease patients. Twenty male patients (age 69.8 ± 2.9 years (mean ± SE)) with end-stage renal disease undergoing maintenance hemodialysis on regular dialysis treatment for 15-71 months participated in this study. A single hemodialysis session, lasting 4.2 ± 0.1 h, resulted in a decrease (P = 0.014) in [BDNF](s) by ~42 % (2,574 ± 322 vs. 1,492 ± 327 pg ml(-1)). This was accompanied by an increase (P 0.05) in [BDNF](pl) and the platelets count were observed after a single dialysis session. Furthermore, basal [BDNF](s) in the chronic kidney disease patients was significantly lower (P = 0.03) when compared to the age-matched control group (n = 23). We have concluded that the observed decrease in serum BDNF level after hemodialysis accompanied by elevated [F(2)-Isoprostanes](pl) and decreased plasma TAC might be caused by enhanced oxidative stress induced by hemodialysis.

  18. Catechins decrease neurological severity score through apoptosis and neurotropic factor pathway in rat traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Retty Ratnawati

    2017-08-01

    Administration of catechins decreased NSS through inhibiting inflammation and apoptosis, as well as induced the neurotrophic factors in rat brain injury. Catechins may serve as a potential intervention for TBI.

  19. [Geomagnetic storm decreases coherence of electric oscillations of human brain while working at the computer].

    Science.gov (United States)

    Novik, O B; Smirnov, F A

    2013-01-01

    The effect of geomagnetic storms at the latitude of Moscow on the electric oscillations of the human brain cerebral cortex was studied. In course of electroencephalogram measurements it was shown that when the voluntary persons at the age of 18-23 years old were performing tasks using a computer during moderate magnetic storm or no later than 24 hrs after it, the value of the coherence function of electric oscillations of the human brain in the frontal and occipital areas in a range of 4.0-7.9 Hz (so-called the theta rhythm oscillations of the human brain) decreased by a factor of two or more, sometimes reaching zero, although arterial blood pressure, respiratory rate and the electrocardiogram registered during electroencephalogram measurements remained within the standard values.

  20. Decreased levels of brain-derived neurotrophic factor in the remitted state of unipolar depressive disorder

    DEFF Research Database (Denmark)

    Hasselbalch, Jacob; Knorr, U; Bennike, B

    2012-01-01

    Decreased levels of peripheral brain-derived neurotrophic factor (BDNF) have been associated with depression. It is uncertain whether abnormally low levels of BDNF in blood are present beyond the depressive state and whether levels of BDNF are associated with the course of clinical illness....

  1. 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.

  2. HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

    Science.gov (United States)

    Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

    2011-01-01

    Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  4. Decrease in fMRI brain activation during working memory performed after sleeping under 10 lux light.

    Science.gov (United States)

    Kang, Seung-Gul; Yoon, Ho-Kyoung; Cho, Chul-Hyun; Kwon, Soonwook; Kang, June; Park, Young-Min; Lee, Eunil; Kim, Leen; Lee, Heon-Jeong

    2016-11-09

    The aim of this study was to investigate the effect of exposure to dim light at night (dLAN) when sleeping on functional brain activation during a working-memory tasks. We conducted the brain functional magnetic resonance imaging (fMRI) analysis on 20 healthy male subjects. All participants slept in a polysomnography laboratory without light exposure on the first and second nights and under a dim-light condition of either 5 or 10 lux on the third night. The fMRI scanning was conducted during n-back tasks after second and third nights. Statistical parametric maps revealed less activation in the right inferior frontal gyrus (IFG) after exposure to 10-lux light. The brain activity in the right and left IFG areas decreased more during the 2-back task than during the 1- or 0-back task in the 10-lux group. The exposure to 5-lux light had no significant effect on brain activities. The exposure to dLAN might influence the brain function which is related to the cognition.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Identification of a set of genes showing regionally enriched expression in the mouse brain

    Directory of Open Access Journals (Sweden)

    Marra Marco A

    2008-07-01

    Full Text Available Abstract Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters ( Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

  7. A clinical case of the schizophrenia-like organic personality syndrome after neck hanging with special reference to the brain positron CT showing the lowered functioning in frontal lobe

    International Nuclear Information System (INIS)

    Koizumi, Junzo; Takeuchi, Tatsuo; Ono, Yukio; Kozuki, Hideki; Iio, Masaaki.

    1985-01-01

    A 21-year-old woman developed schizophrenia-like organic personality syndrome subsequent to neck hanging. Brain positron CT with 11 CO, 15 O 2 , and C 15 O 2 showed decreased blood flow in the frontal lobe, decreased glucose metabolism in the frontal and lateral lobes, decreased cerebral metabolic rate of oxygen, and decreased cerebral blood flow, suggesting lowered functioning in the frontal lobe. Since these CT findings were very similar to those in patients with chronic sphizophrenia, clinical symptoms of sphizophrenia seems to be related to lowered functioning in the frontal lobe. (Namekawa, K.)

  8. Chronic depression is associated with a pronounced decrease in serum brain-derived neurotrophic factor over time

    NARCIS (Netherlands)

    Bus, B.A.A.; Molendijk, M.L.; Tendolkar, I.; Penninx, B.W.J.H.; Prickaerts, J.; Elzinga, B.M.; Voshaar, R.C.O.

    2015-01-01

    One of the leading neurobiological hypotheses on depression states that decreased expression of brain-derived neurotrophic factor (BDNF) contributes to depression. This is supported by consistent findings of low serum BDNF levels in depressed patients compared with non-depressed controls. Whereas it

  9. Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice

    Directory of Open Access Journals (Sweden)

    Dantzer Robert

    2011-02-01

    Full Text Available Abstract Exogenous administration of insulin-like growth factor (IGF-I has anti-depressant properties in rodent models of depression. However, nothing is known about the anti-depressant properties of IGF-I during inflammation, nor have mechanisms by which IGF-I alters behavior following activation of the innate immune system been clarified. We hypothesized that central IGF-I would diminish depressive-like behavior on a background of an inflammatory response and that it would do so by inducing expression of the brain-derived neurotrophic factor (BDNF while decreasing pro-inflammatory cytokine expression in the brain. IGF-I (1,000 ng was administered intracerebroventricularly (i.c.v. to CD-1 mice. Mice were subsequently given lipopolysaccharide i.c.v. (LPS, 10 ng. Sickness and depressive-like behaviors were assessed followed by analysis of brain steady state mRNA expression. Central LPS elicited typical transient signs of sickness of mice, including body weight loss, reduced feed intake and decreased social exploration toward a novel juvenile. Similarly, LPS increased time of immobility in the tail suspension test (TST. Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS. To elucidate the mechanisms underlying the anti-depressant action of IGF-I, we quantified steady-state mRNA expression of inflammatory mediators in whole brain using real-time RT-PCR. LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß, tumor necrosis factor-(TNFα, inducible nitric oxide synthase (iNOS and glial fibrillary acidic protein (GFAP. Moreover, IGF-I increased expression of BDNF. These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity. These actions of IGF-I parallel its ability to diminish depressive-like behavior.

  10. Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice

    Science.gov (United States)

    2011-01-01

    Exogenous administration of insulin-like growth factor (IGF)-I has anti-depressant properties in rodent models of depression. However, nothing is known about the anti-depressant properties of IGF-I during inflammation, nor have mechanisms by which IGF-I alters behavior following activation of the innate immune system been clarified. We hypothesized that central IGF-I would diminish depressive-like behavior on a background of an inflammatory response and that it would do so by inducing expression of the brain-derived neurotrophic factor (BDNF) while decreasing pro-inflammatory cytokine expression in the brain. IGF-I (1,000 ng) was administered intracerebroventricularly (i.c.v.) to CD-1 mice. Mice were subsequently given lipopolysaccharide i.c.v. (LPS, 10 ng). Sickness and depressive-like behaviors were assessed followed by analysis of brain steady state mRNA expression. Central LPS elicited typical transient signs of sickness of mice, including body weight loss, reduced feed intake and decreased social exploration toward a novel juvenile. Similarly, LPS increased time of immobility in the tail suspension test (TST). Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS. To elucidate the mechanisms underlying the anti-depressant action of IGF-I, we quantified steady-state mRNA expression of inflammatory mediators in whole brain using real-time RT-PCR. LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß), tumor necrosis factor-(TNF)α, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP). Moreover, IGF-I increased expression of BDNF. These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity. These actions of IGF-I parallel its ability to diminish depressive-like behavior. PMID:21306618

  11. Rapid decreases in preoptic aromatase activity and brain monoamine concentrations after engaging in male sexual behavior.

    Science.gov (United States)

    Cornil, C A; Dalla, C; Papadopoulou-Daifoti, Z; Baillien, M; Dejace, C; Ball, G F; Balthazart, J

    2005-09-01

    In Japanese quail, as in rats, the expression of male sexual behavior over relatively long time periods (days to weeks) is dependent on the local production of estradiol in the preoptic area via the aromatization of testosterone. On a short-term basis (minutes to hours), central actions of dopamine as well as locally produced estrogens modulate behavioral expression. In rats, a view of and sexual interaction with a female increase dopamine release in the preoptic area. In quail, in vitro brain aromatase activity (AA) is rapidly modulated by calcium-dependent phosphorylations that are likely to occur in vivo as a result of changes in neurotransmitter activity. Furthermore, an acute estradiol injection rapidly stimulates copulation in quail, whereas a single injection of the aromatase inhibitor vorozole rapidly inhibits this behavior. We hypothesized that brain aromatase and dopaminergic activities are regulated in quail in association with the expression of male sexual behavior. Visual access as well as sexual interactions with a female produced a significant decrease in brain AA, which was maximal after 5 min. This expression of sexual behavior also resulted in a significant decrease in dopaminergic as well as serotonergic activity after 1 min, which returned to basal levels after 5 min. These results demonstrate for the first time that AA is rapidly modulated in vivo in parallel with changes in dopamine activity. Sexual interactions with the female decreased aromatase and dopamine activities. These data challenge established views about the causal relationships among dopamine, estrogen action, and male sexual behavior.

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

    Science.gov (United States)

    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.

  13. Addiction: decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain's control circuit.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Fowler, Joanna S; Tomasi, Dardo; Telang, Frank; Baler, Ruben

    2010-09-01

    Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is largely a voluntary behavior, continued drug use can eventually impair neuronal circuits in the brain that are involved in free will, turning drug use into an automatic compulsive behavior. The ability of addictive drugs to co-opt neurotransmitter signals between neurons (including dopamine, glutamate, and GABA) modifies the function of different neuronal circuits, which begin to falter at different stages of an addiction trajectory. Upon exposure to the drug, drug cues or stress this results in unrestrained hyperactivation of the motivation/drive circuit that results in the compulsive drug intake that characterizes addiction.

  14. Contralateral thalamic hypoperfusion on brain perfusion SPECT

    International Nuclear Information System (INIS)

    Lee, Seok Mo; Bae, Sang Kyun; Yoo, Kyung Moo; Yum, Ha Yong

    2000-01-01

    Brain perfusion single photon emission computed tomography (SPECT) is useful for the localization of cerebrovascular lesion and sometimes reveals more definite lesion than radiologic imaging modality such as CT or MRI does. The purpose of this study was to evaluate the diagnostic usefulness of brain perfusion SPECT in patients with hemisensory impairment. Thirteen consecutive patients (M:F= 8:5, mean age = 48) who has hemisensory impairment were included. Brain perfusion SPECT was performed after intravenous injection of 1110 MBq of Tc-99m ECD. The images were obtained using a dual-head gamma camera with ultra-high resolution collimator. Semiquantitative analysis was performed after placing multiple ROIs on cerebral cortex, basal ganglia, thalamus and cerebellum. There were 10 patients with left hemisensory impairment and 3 patients with right-sided symptom. Only 2 patients revealed abnormal signal change in the thalamus on MRI. But brain perfusion SPECT showed decreased perfusion in the thalamus in 9 patients. Six patients among 10 patients with left hemisensory impairment revealed decreased perfusion in the contralateral thalamus on brain SPECT. The other 4 patients revealed no abnormality. Two patients among 3 patients with right hemisensory impairment also showed decreased perfusion in the contralateral thalamus on brain SPECT. One patients with right hemisensory impairment showed ipsilateral perfusion decrease. Two patients who had follow-up brain perfusion SEPCT after treatment revealed normalization of perfusion in the thalamus. Brain perfusion SPECT might be a useful tool in diagnosing patients with hemisensory impairment

  15. Lutein and preterm infants with decreased concentrations of brain carotenoids.

    Science.gov (United States)

    Vishwanathan, Rohini; Kuchan, Matthew J; Sen, Sarbattama; Johnson, Elizabeth J

    2014-11-01

    Lutein and zeaxanthin are dietary carotenoids that may influence visual and cognitive development. The objective of this study was to provide the first data on distribution of carotenoids in the infant brain and compare concentrations in preterm and term infants. Voluntarily donated brain tissues from 30 infants who died during the first 1.5 years of life were obtained from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Brain and Tissue Bank. Tissues (hippocampus and prefrontal, frontal, auditory, and occipital cortices) were extracted using standard lipid extraction procedures and analyzed using reverse-phase high-pressure liquid chromatography. Lutein, zeaxanthin, cryptoxanthin, and β-carotene were the major carotenoids found in the infant brain tissues. Lutein was the predominant carotenoid accounting for 59% of total carotenoids. Preterm infants (n = 8) had significantly lower concentrations of lutein, zeaxanthin, and cryptoxanthin in their brain compared with term infants (n = 22) despite similarity in postmenstrual age. Among formula-fed infants, preterm infants (n = 3) had lower concentrations of lutein and zeaxanthin compared with term infants (n = 5). Brain lutein concentrations were not different between breast milk-fed (n = 3) and formula-fed (n = 5) term decedents. In contrast, term decedents with measurable brain cryptoxanthin, a carotenoid that is inherently low in formula, had higher brain lutein, suggesting that the type of feeding is an important determinant of brain lutein concentrations. These data reveal preferential accumulation and maintenance of lutein in the infant brain despite underrepresentation in the typical infant diet. Further investigation on the impact of lutein on neural development in preterm infants is warranted.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  18. Decreased Rhes mRNA levels in the brain of patients with Parkinson's disease and MPTP-treated macaques.

    Directory of Open Access Journals (Sweden)

    Francesco Napolitano

    Full Text Available In rodent and human brains, the small GTP-binding protein Rhes is highly expressed in virtually all dopaminoceptive striatal GABAergic medium spiny neurons, as well as in large aspiny cholinergic interneurons, where it is thought to modulate dopamine-dependent signaling. Consistent with this knowledge, and considering that dopaminergic neurotransmission is altered in neurological and psychiatric disorders, here we sought to investigate whether Rhes mRNA expression is altered in brain regions of patients with Parkinson's disease (PD, Schizophrenia (SCZ, and Bipolar Disorder (BD, when compared to healthy controls (about 200 post-mortem samples. Moreover, we performed the same analysis in the putamen of non-human primate Macaca Mulatta, lesioned with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP. Overall, our data indicated comparable Rhes mRNA levels in the brain of patients with SCZ and BD, and their respective healthy controls. In sharp contrast, the putamen of patients suffering from PD showed a significant 35% reduction of this transcript, compared to healthy subjects. Interestingly, in line with observations obtained in humans, we found 27% decrease in Rhes mRNA levels in the putamen of MPTP-treated primates. Based on the established inhibitory influence of Rhes on dopamine-related responses, we hypothesize that its striatal downregulation in PD patients and animal models of PD might represent an adaptive event of the dopaminergic system to functionally counteract the reduced nigrostriatal innervation.

  19. Brain morphometry shows effects of long-term musical practice in middle-aged keyboard players

    Directory of Open Access Journals (Sweden)

    Hanna eGärtner

    2013-09-01

    Full Text Available To what extent does musical practice change the structure of the brain? In order to understand how long-lasting musical training changes brain structure, 20 male right-handed, middle-aged professional musicians and 19 matched controls were investigated. Among the musicians, 13 were pianists or organists with intensive practice regimes. The others were either music teachers at schools or string instrumentalists, who had studied the piano at least as a subsidiary subject, and practiced less intensively. The study was based on T1-weighted MR images, which were analyzed using Deformation Field Morphometry. Cytoarchitectonic probabilistic maps of cortical areas and subcortical nuclei as well as myeloarchitectonic maps of fiber tracts were used as regions of interest to compare volume differences in the brains of musicians and controls. In addition, maps of voxel-wise volume differences were computed and analyzed.Musicians showed a significantly better symmetric motor performance as well as a greater capability of controlling hand independence than controls. Structural MRI-data revealed significant volumetric differences between the brains of keyboard players, who practiced intensively and controls in right sensorimotor areas and the corticospinal tract as well as in the entorhinal cortex and the left superior parietal lobule. Moreover, they showed also larger volumes in a comparable set of regions than the less intensively practicing musicians. The structural changes in the sensory and motor systems correspond well to the behavioral results, and can be interpreted in terms of plasticity as a result of intensive motor training. Areas of the superior parietal lobule and the entorhinal cortex might be enlarged in musicians due to their special skills in sight-playing and memorizing of scores. In conclusion, intensive and specific musical training seems to have an impact on brain structure, not only during the sensitive period of childhood but throughout

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

    Science.gov (United States)

    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

  1. Cerebral ischemic injury decreases α-synuclein expression in brain tissue and glutamate-exposed HT22 cells.

    Science.gov (United States)

    Koh, Phil-Ok

    2017-09-01

    α-Synuclein is abundantly expressed in neuronal tissue, plays an essential role in the pathogenesis of neurodegenerative disorders, and exerts a neuroprotective effect against oxidative stress. Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. In this study, we examined α-synuclein expression in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury and neuronal cells damaged by glutamate treatment. MCAO surgical operation was performed on male Sprague-Dawley rats, and brain samples were isolated 24 hours after MCAO. We confirmed neurological behavior deficit, infarction area, and histopathological changes following MCAO injury. A proteomic approach and Western blot analysis demonstrated a decrease in α-synuclein in the cerebral cortices after MCAO injury. Moreover, glutamate treatment induced neuronal cell death and decreased α-synuclein expression in a hippocampal-derived cell line in a dose-dependent manner. It is known that α-synuclein regulates neuronal survival, and low levels of α-synuclein expression result in cytotoxicity. Thus, these results suggest that cerebral ischemic injury leads to a reduction in α-synuclein and consequently causes serious brain damage.

  2. The 28-day exposure to fenpropathrin decreases locomotor activity and reduces activity of antioxidant enzymes in mice brains.

    Science.gov (United States)

    Nieradko-Iwanicka, Barbara; Borzęcki, Andrzej

    2016-04-01

    Fenpropathrin (Fen) is a pyrethroid (Pyr) insecticide. Pyrs are used in veterinary medicine, in agriculture and for domestic purposes. As their use increases, new questions about their side effects and mode of action in non-target organisms arise. The objective of this work was to characterize dose-response relationship for in vivo motor function and memory in mice exposed to Fen for 28 days and to assess its influence on activity of antioxidant enzymes in mice brains. The experiment was performed using 64 female mice. Fen at the dose of 11.9mg/kg of body mass, 5.95mg/kg or 2.38mg/kg was administered ip to the mice for 28 consecutive days. Motor function and spatial working memory were tested on days 7, 14 and 28. On day 29, the animals were sacrificed and brains were used to determine activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Fen significantly decreased locomotor activity in mice receiving the highest dose at every stage of the experiment. Lower doses reduced locomotion on days 7 and 14. Fen did not produce memory impairment. A decrease in activities of SOD and GPx was recorded in mice brains. The decrease of SOD activity in mice brains results from direct inhibition of the enzyme by Fen and/or increased utilization due to excessive free radical formation in conditions of Fen-induced oxidative stress. The reduction in GPx activity is probably due to limited glutathione availability. The reduced locomotor activity is a behavioral demonstration of Fen-induced damage in the dopaminergic system. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  3. Prenatal Protein Malnutrition Decreases KCNJ3 and 2DG Activity in Rat Prefrontal Cortex

    Science.gov (United States)

    Amaral, A.C.; Jakovcevski, M.; McGaughy, J.A.; Calderwood, S.K.; Mokler, D.J.; Rushmore, R.J.; Galler, J.R.; Akbarian, S.A.; Rosene, D.L.

    2014-01-01

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with 14C-2-deoxyglucose. Results showed decreased activation in PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity. PMID:25446346

  4. Phosphatidylcholine 36:1 concentration decreases along with demyelination in the cuprizone animal model and post-mortem of multiple sclerosis brain tissue.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Hildebrand, Kayla D; Nyamoya, Stella D; Amor, Sandra; Bazinet, Richard P; Kipp, Markus

    2018-03-25

    Multiple sclerosis (MS) is a demyelinating and inflammatory disease. Myelin is enriched in lipids, and more specifically, oleic acid. The goal of this study was to evaluate the concentration of oleic acid following demyelination and remyelination in the cuprizone model, test if these changes occurred in specific lipid species, and whether differences in the cuprizone model correlate with changes observed in post-mortem human brains. Eight-week-old C57Bl/6 mice were fed a 0.2% cuprizone diet for 5 weeks and some animals allowed to recover for 11 days. Demyelination, inflammation, and lipid concentrations were measured in the corpus callosum. Standard fatty acid techniques and liquid chromatography combined with tandem mass spectrometry were performed to measure concentrations of fatty acids in total brain lipids and a panel of lipid species within the phosphatidylcholine (PC). Similar measurements were conducted in post-mortem brain tissues of MS patients and were compared to healthy controls. Five weeks of cuprizone administration resulted in demyelination followed by significant remyelination after 11 days of recovery. Compared to control, oleic acid was decreased after 5 weeks of cuprizone treatment and increased during the recovery phase. This decrease in oleic acid was associated with a specific decrease in the PC 36:1 pool. Similar results were observed in human post-mortem brains. Decreases in myelin content in the cuprizone model was accompanied with decreases in oleic acid concentration and is associated with PC 36:1 suggesting that specific lipids could be a potential biomarker for myelin degeneration. The biological relevance of oleic acid for disease progression remains to be verified. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Decreased Complexity in Alzheimer's Disease: Resting-State fMRI Evidence of Brain Entropy Mapping

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2017-11-01

    Full Text Available Alzheimer's disease (AD is a frequently observed, irreversible brain function disorder among elderly individuals. Resting-state functional magnetic resonance imaging (rs-fMRI has been introduced as an alternative approach to assessing brain functional abnormalities in AD patients. However, alterations in the brain rs-fMRI signal complexities in mild cognitive impairment (MCI and AD patients remain unclear. Here, we described the novel application of permutation entropy (PE to investigate the abnormal complexity of rs-fMRI signals in MCI and AD patients. The rs-fMRI signals of 30 normal controls (NCs, 33 early MCI (EMCI, 32 late MCI (LMCI, and 29 AD patients were obtained from the Alzheimer's disease Neuroimaging Initiative (ADNI database. After preprocessing, whole-brain entropy maps of the four groups were extracted and subjected to Gaussian smoothing. We performed a one-way analysis of variance (ANOVA on the brain entropy maps of the four groups. The results after adjusting for age and sex differences together revealed that the patients with AD exhibited lower complexity than did the MCI and NC controls. We found five clusters that exhibited significant differences and were distributed primarily in the occipital, frontal, and temporal lobes. The average PE of the five clusters exhibited a decreasing trend from MCI to AD. The AD group exhibited the least complexity. Additionally, the average PE of the five clusters was significantly positively correlated with the Mini-Mental State Examination (MMSE scores and significantly negatively correlated with Functional Assessment Questionnaire (FAQ scores and global Clinical Dementia Rating (CDR scores in the patient groups. Significant correlations were also found between the PE and regional homogeneity (ReHo in the patient groups. These results indicated that declines in PE might be related to changes in regional functional homogeneity in AD. These findings suggested that complexity analyses using PE

  6. 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.

    Science.gov (United States)

    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.

  7. Methylphenidate decreased the amount of glucose needed by the brain to perform a cognitive task.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    2008-04-01

    Full Text Available The use of stimulants (methylphenidate and amphetamine as cognitive enhancers by the general public is increasing and is controversial. It is still unclear how they work or why they improve performance in some individuals but impair it in others. To test the hypothesis that stimulants enhance signal to noise ratio of neuronal activity and thereby reduce cerebral activity by increasing efficiency, we measured the effects of methylphenidate on brain glucose utilization in healthy adults. We measured brain glucose metabolism (using Positron Emission Tomography and 2-deoxy-2[18F]fluoro-D-glucose in 23 healthy adults who were tested at baseline and while performing an accuracy-controlled cognitive task (numerical calculations given with and without methylphenidate (20 mg, oral. Sixteen subjects underwent a fourth scan with methylphenidate but without cognitive stimulation. Compared to placebo methylphenidate significantly reduced the amount of glucose utilized by the brain when performing the cognitive task but methylphenidate did not affect brain metabolism when given without cognitive stimulation. Whole brain metabolism when the cognitive task was given with placebo increased 21% whereas with methylphenidate it increased 11% (50% less. This reflected both a decrease in magnitude of activation and in the regions activated by the task. Methylphenidate's reduction of the metabolic increases in regions from the default network (implicated in mind-wandering was associated with improvement in performance only in subjects who activated these regions when the cognitive task was given with placebo. These results corroborate prior findings that stimulant medications reduced the magnitude of regional activation to a task and in addition document a "focusing" of the activation. This effect may be beneficial when neuronal resources are diverted (i.e., mind-wandering or impaired (i.e., attention deficit hyperactivity disorder, but it could be detrimental when

  8. Transient postnatal fluoxetine decreases brain concentrations of 20-HETE and 15-epi-LXA4, arachidonic acid metabolites in adult mice.

    Science.gov (United States)

    Yuan, Zhi-Xin; Rapoport, Stanley I

    2015-10-01

    Transient postnatal exposure of rodents to the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine alters behavior and brain 5-HT neurotransmission during adulthood, and also reduces brain arachidonic (ARA) metabolic consumption and protein level of the ARA metabolizing enzyme, cytochrome P4504A (CYP4A). Brain 20-hydroxyeicosatetraenoic acid (20-HETE), converted by CYP4A from ARA, will be reduced in adult mice treated transiently and postnatally with fluoxetine. Male mice pups were injected i.p. daily with fluoxetine (10mg/kg) or saline during P4-P21. At P90 their brain was high-energy microwaved and analyzed for 20-HETE and six other ARA metabolites by enzyme immunoassay. Postnatal fluoxetine vs. saline significantly decreased brain concentrations of 20-HETE (-70.3%) and 15-epi-lipoxin A4 (-60%) in adult mice, but did not change other eicosanoid concentrations. Behavioral changes in adult mice treated postnatally with fluoxetine may be related to reduced brain ARA metabolism involving CYP4A and 20-HETE formation. Published by Elsevier Ltd.

  9. Bupropion Shows Different Effects on Brain Functional Connectivity in Patients With Internet-Based Gambling Disorder and Internet Gaming Disorder

    Directory of Open Access Journals (Sweden)

    Sujin Bae

    2018-04-01

    Full Text Available IntroductionInternet gaming disorder (IGD and gambling disorder (GD share similar clinical characteristics but show different brain functional connectivity patterns. Bupropion is known to be effective for the treatment of patients with IGD and GD. We hypothesized that bupropion may be effective for the treatment of Internet-based gambling disorder (ibGD and IGD and that the connections between the default mode network (DMN and cognitive control network (CCN would be different between ibGD and IGD patients after 12 weeks of bupropion treatment.Methods16 patients with IGD, 15 patients with ibGD, and 15 healthy subjects were recruited in this study. At baseline and after 12 weeks of bupropion treatment, the clinical symptoms of patients with IGD or ibGD were assessed, and brain activity was evaluated using resting state functional magnetic resonance imaging.ResultsAfter the 12-week bupropion treatment, clinical symptoms, including the severity of IGD or GD, depressive symptoms, attention, and impulsivity improved in both groups. In the IGD group, the functional connectivity (FC within the posterior DMN as well as the FC between the DMN and the CCN decreased following treatment. Moreover, the FC within the DMN in the IGD group was positively correlated with changes in Young Internet Addiction Scale scores after the bupropion treatment period. In the ibGD group, the FC within the posterior DMN decreased while the FC within the CCN increased after the bupropion treatment period. Moreover, the FC within the CCN in the ibGD group was significantly greater than that in the IGD group.ConclusionBupropion was effective in improving clinical symptoms in patients with IGD and ibGD. However, there were differences in the pharmacodynamics between the two groups. After 12 weeks of bupropion treatment, the FC within the DMN as well as between the DMN and CCN decreased in patients with IGD, whereas the FC within the CCN increased in patients with ibGD.

  10. Bupropion Shows Different Effects on Brain Functional Connectivity in Patients With Internet-Based Gambling Disorder and Internet Gaming Disorder.

    Science.gov (United States)

    Bae, Sujin; Hong, Ji Sun; Kim, Sun Mi; Han, Doug Hyun

    2018-01-01

    Internet gaming disorder (IGD) and gambling disorder (GD) share similar clinical characteristics but show different brain functional connectivity patterns. Bupropion is known to be effective for the treatment of patients with IGD and GD. We hypothesized that bupropion may be effective for the treatment of Internet-based gambling disorder (ibGD) and IGD and that the connections between the default mode network (DMN) and cognitive control network (CCN) would be different between ibGD and IGD patients after 12 weeks of bupropion treatment. 16 patients with IGD, 15 patients with ibGD, and 15 healthy subjects were recruited in this study. At baseline and after 12 weeks of bupropion treatment, the clinical symptoms of patients with IGD or ibGD were assessed, and brain activity was evaluated using resting state functional magnetic resonance imaging. After the 12-week bupropion treatment, clinical symptoms, including the severity of IGD or GD, depressive symptoms, attention, and impulsivity improved in both groups. In the IGD group, the functional connectivity (FC) within the posterior DMN as well as the FC between the DMN and the CCN decreased following treatment. Moreover, the FC within the DMN in the IGD group was positively correlated with changes in Young Internet Addiction Scale scores after the bupropion treatment period. In the ibGD group, the FC within the posterior DMN decreased while the FC within the CCN increased after the bupropion treatment period. Moreover, the FC within the CCN in the ibGD group was significantly greater than that in the IGD group. Bupropion was effective in improving clinical symptoms in patients with IGD and ibGD. However, there were differences in the pharmacodynamics between the two groups. After 12 weeks of bupropion treatment, the FC within the DMN as well as between the DMN and CCN decreased in patients with IGD, whereas the FC within the CCN increased in patients with ibGD.

  11. A single-nucleotide polymorphism of human neuropeptide s gene originated from Europe shows decreased bioactivity.

    Directory of Open Access Journals (Sweden)

    Cheng Deng

    Full Text Available Using accumulating SNP (Single-Nucleotide Polymorphism data, we performed a genome-wide search for polypeptide hormone ligands showing changes in the mature regions to elucidate genotype/phenotype diversity among various human populations. Neuropeptide S (NPS, a brain peptide hormone highly conserved in vertebrates, has diverse physiological effects on anxiety, fear, hyperactivity, food intake, and sleeping time through its cognate receptor-NPSR. Here, we report a SNP rs4751440 (L(6-NPS causing non-synonymous substitution on the 6(th position (V to L of the NPS mature peptide region. L(6-NPS has a higher allele frequency in Europeans than other populations and probably originated from European ancestors ~25,000 yrs ago based on haplotype analysis and Approximate Bayesian Computation. Functional analyses indicate that L(6-NPS exhibits a significant lower bioactivity than the wild type NPS, with ~20-fold higher EC50 values in the stimulation of NPSR. Additional evolutionary and mutagenesis studies further demonstrate the importance of the valine residue in the 6(th position for NPS functions. Given the known physiological roles of NPS receptor in inflammatory bowel diseases, asthma pathogenesis, macrophage immune responses, and brain functions, our study provides the basis to elucidate NPS evolution and signaling diversity among human populations.

  12. Brain perfusion spect imaging with sup 99m Tc-HM-PAO in Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Wenzhong, Song; Xiangtong, Lin [Shanghai Medical Univ. (China). Huashan Hospital

    1991-02-01

    Forty patients with Parkinson's disease were studied using {sup 99m}Tc-HM-PAO brain perfusion SPECT. 62.5% (25 cases) showed abnormal blood perfusion. Among them 55% showed local decreased blood perfusion of cerebral cortex, 22% showed asymmetric decreased blood perfusion in basal gaglia, 10% showed decreased uptake of tracer in cerebellum. The pathophysiologic basis of the abnormality of brain blood perfusion were briefly discussed.

  13. Brain perfusion in acute and chronic hyperglycemia in rats

    International Nuclear Information System (INIS)

    Kikano, G.E.; LaManna, J.C.; Harik, S.I.

    1989-01-01

    Recent studies show that acute and chronic hyperglycemia cause a diffuse decrease in regional cerebral blood flow and that chronic hyperglycemia decreases the brain L-glucose space. Since these changes can be caused by a decreased density of perfused brain capillaries, we used 30 adult male Wistar rats to study the effect of acute and chronic hyperglycemia on (1) the brain intravascular space using radioiodinated albumin, (2) the anatomic density of brain capillaries using alkaline phosphatase histochemistry, and (3) the fraction of brain capillaries that are perfused using the fluorescein isothiocyanate-dextran method. Our results indicate that acute and chronic hyperglycemia do not affect the brain intravascular space nor the anatomic density of brain capillaries. Also, there were no differences in capillary recruitment among normoglycemic, acutely hyperglycemic, and chronically hyperglycemic rats. These results suggest that the shrinkage of the brain L-glucose space in chronic hyperglycemia is more likely due to changes in the blood-brain barrier permeability to L-glucose

  14. 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.

  15. 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.

  16. Whole brain resting-state analysis reveals decreased functional connectivity in major depression

    Directory of Open Access Journals (Sweden)

    Ilya M. Veer

    2010-09-01

    Full Text Available Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within six months before inclusion and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxelwise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: 1 decreased bilateral amygdala and left anterior insula connectivity in an affective network, 2 reduced connectivity of the left frontal pole in a network associated with attention and working memory, and 3 decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or grey matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.

  17. Inhibiting HIF-1α Decreases Expression of TNF-α and Caspase-3 in Specific Brain Regions Exposed Kainic Acid-Induced Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Jixue Yang

    2016-01-01

    Full Text Available Background/Aims: A recent study demonstrates that pro-inflammatory cytokines (PICs, i.e., IL-1β, IL-6 and TNF-α in specific brain regions of rats play a role in regulating kainic acid (KA-induced status epilepticus (SE via a GABAergic mechanism. The purposes of this report were to examine contributions of hypoxia inducible factor subtype 1α (HIF-1α to expression of PICs in these specific brain regions in epileptic rats. Particularly, we investigated the parietal cortex, hippocampus and amygdala. In addition, we further examined expression of Caspase-3 indicating cell apoptosis in those brain regions of epileptic rats after infusing 2-methoxyestradiol (2-MET, inhibitor of HIF-1α and etanercept (TNF-α receptor antagonist. Methods: ELISA was used to determine the levels of HIF-1α and PICs and western blot analysis was used to examine Caspase-3 expression. Results: Our data show that HIF-1α was significantly increased in the parietal cortex, hippocampus and amygdala 1, 3 and 7 days after induction of SE (Pvs. control rats. Our results also show that inhibiting HIF-1α by central infusion of 2-MET significantly decreased the amplified TNF-α expression in these brain regions evoked by SE (Pvs. vehicle control, but did not modify IL-1β and IL-6. Our results demonstrate that 2-MET and etanercept attenuated an increase in Caspase-3 evoked by SE. Conclusion: Overall, we suggest that HIF-1α activated by SE is likely to contribute to epileptic activity via a TNF-α pathway, which has pharmacological implications to target specific HIF-1α and TNF-α pathways for neuronal dysfunction and vulnerability related to epilepsy.

  18. Electrical stunning and exsanguination decrease the extracellular volume in the broiler brain as studied with brain impedance recordings

    NARCIS (Netherlands)

    Savenije, B; Lambooij, E; Pieterse, C; Korf, J

    Electrical stunning in the process of slaughtering poultry is used to induce unconsciousness and immobilize the animal for easier processing. Unconsciousness is a function of brain damage. Brain damage has been studied with brain impedance recordings under ischemic conditions. This experiment

  19. Loss of Brain Aerobic Glycolysis in Normal Human Aging.

    Science.gov (United States)

    Goyal, Manu S; Vlassenko, Andrei G; Blazey, Tyler M; Su, Yi; Couture, Lars E; Durbin, Tony J; Bateman, Randall J; Benzinger, Tammie L-S; Morris, John C; Raichle, Marcus E

    2017-08-01

    The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

    Science.gov (United States)

    Ding, Xiao-Qi; Maudsley, Andrew A; Sabati, Mohammad; Sheriff, Sulaiman; Schmitz, Birte; Schütze, Martin; Bronzlik, Paul; Kahl, Kai G; Lanfermann, Heinrich

    2016-08-15

    Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Interleukin 6 modulates acetylcholinesterase activity of brain neurons

    International Nuclear Information System (INIS)

    Clarencon, D.; Multon, E.; Galonnier, M.; Estrade, M.; Fournier, C.; Mathieu, J.; Mestries, J.C.; Testylier, G.; Fatome, M.

    1995-01-01

    Classically, radiation injuries results in a peripheral inflammatory process, and we have previously observed an early systemic interleukin 6 (IL-6) release following whole-body irradiation. Besides, we have demonstrated an early decrease of rat or primate brain acetylcholinesterase (AChE) activity a gamma exposure. The object of the present study is to find possible IL-6 systemic effects on the brain AChE activity. We show that, though intravenous (i.v.) or intra-cerebro-ventricular (ICV) injection of IL-6 can induce a drop in rat brain AChE activity, this cytokine induces only a slight decrease of the AChE release in cultured brain cells. (author)

  2. Decreased resting functional connectivity after traumatic brain injury in the rat.

    Directory of Open Access Journals (Sweden)

    Asht Mangal Mishra

    Full Text Available Traumatic brain injury (TBI contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG-functional magnetic resonance imaging (fMRI was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and

  3. The brain matures with stronger functional connectivity and decreased randomness of its network.

    Directory of Open Access Journals (Sweden)

    Dirk J A Smit

    Full Text Available We investigated the development of the brain's functional connectivity throughout the life span (ages 5 through 71 years by measuring EEG activity in a large population-based sample. Connectivity was established with Synchronization Likelihood. Relative randomness of the connectivity patterns was established with Watts and Strogatz' (1998 graph parameters C (local clustering and L (global path length for alpha (~10 Hz, beta (~20 Hz, and theta (~4 Hz oscillation networks. From childhood to adolescence large increases in connectivity in alpha, theta and beta frequency bands were found that continued at a slower pace into adulthood (peaking at ~50 yrs. Connectivity changes were accompanied by increases in L and C reflecting decreases in network randomness or increased order (peak levels reached at ~18 yrs. Older age (55+ was associated with weakened connectivity. Semi-automatically segmented T1 weighted MRI images of 104 young adults revealed that connectivity was significantly correlated to cerebral white matter volume (alpha oscillations: r = 33, p<01; theta: r = 22, p<05, while path length was related to both white matter (alpha: max. r = 38, p<001 and gray matter (alpha: max. r = 36, p<001; theta: max. r = 36, p<001 volumes. In conclusion, EEG connectivity and graph theoretical network analysis may be used to trace structural and functional development of the brain.

  4. 99mTc-HMPAO Brain SPECT in Patients with Post-Traumatic Organic Mental Disorder

    International Nuclear Information System (INIS)

    Lee, Kang Wook; Lee, Dong Jin; Shong, Min Ho; Kang, Min Hee; Ghi, Ick Sung; Shin, Young Tai; Ro, Heung Kyu

    1994-01-01

    It is well known that 99m Tc-HMPAO brain SPECT can reflect the functional lesions better than X-ray computerized tomography(CT) and magnetic resonance imaging(MRI) in the cerebral disorders. In order to evaluate the clinical utilities of 99m Tc-HMPAO brain SPECT in patients with post-traumatic chronic organic mental disorder(OMD). We included 28 patients diagnosed as OMD in department of psychiatry after traumatic head injury. And we compared the results of 99m Tc-HMPAO SPECT with those of MRI, EEG and MINI mental status examination(MMSE). The results were as follows 1) All patients diagnosed as OMD showed diffuse or focal decreased cerebral perfusion on 99m Tc-HMPAO SPECT. 2) Most frequent lesion on brain 99m Tc-HMPAO SPECT was decreased perfusion on both frontal lobe. And most frequent lesion on brain 99m Tc-HMPAO SPECT was decreased perfusion on both frontal lobe. And most frequent lesion on brain 99m Tc-HMPAO SPECT showing normal brain MRI result was also decreased both frontal perfusion. 3) Eight of 28 patients showed focal brain MRI lesions(4 small frontal hygroma, 3 small cerebral infarction and 1 cerebellar encephalomalacia) which were not detected in brain 99m Tc-HMPAO SPECT. 4) The patients showing less than 20 points on MMSE disclosed abnormal results of EEG more frequently than those disclosing more than 20 points. In conclusion, we think that 99m Tc-HMPAO brain SPECT is sensitive method to detect functional lesions of the brains in patients with chronic post-traumatic organic mental disorder.

  5. Neutral genetic variation in adult Chinook salmon (Oncorhynchus tshawytscha) affects brain-to-body trade-off and brain laterality

    Science.gov (United States)

    Heath, Daniel D.; Higgs, Dennis M.

    2017-01-01

    Low levels of heterozygosity can have detrimental effects on life history and growth characteristics of organisms but more subtle effects such as those on trade-offs of expensive tissues and morphological laterality, especially of the brain, have not been explicitly tested. The objective of the current study was to investigate how estimated differences in heterozygosity may potentially affect brain-to-body trade-offs and to explore how these heterozygosity differences may affect differential brain growth, focusing on directional asymmetry in adult Chinook salmon (Oncorhynchus tshawytscha) using the laterality and absolute laterality indices. Level of inbreeding was estimated as mean microsatellite heterozygosity resulting in four ‘inbreeding level groups’ (Very High, High, Medium, Low). A higher inbreeding level corresponded with a decreased brain-to-body ratio, thus a decrease in investment in brain tissue, and also showed a decrease in the laterality index for the cerebellum, where the left hemisphere was larger than the right across all groups. These results begin to show the role that differences in heterozygosity may play in differential tissue investment and in morphological laterality, and may be useful in two ways. Firstly, the results may be valuable for restocking programmes that wish to emphasize brain or body growth when crossing adults to generate individuals for release, as we show that genetic variation does affect these trade-offs. Secondly, this study is one of the first examinations to test the hypothesized relationship between genetic variation and laterality, finding that in Chinook salmon there is potential for an effect of inbreeding on lateralized morphology, but not in the expected direction. PMID:29308240

  6. Algebraic connectivity of brain networks shows patterns of segregation leading to reduced network robustness in Alzheimer's disease

    Science.gov (United States)

    Daianu, Madelaine; Jahanshad, Neda; Nir, Talia M.; Leonardo, Cassandra D.; Jack, Clifford R.; Weiner, Michael W.; Bernstein, Matthew A.; Thompson, Paul M.

    2015-01-01

    Measures of network topology and connectivity aid the understanding of network breakdown as the brain degenerates in Alzheimer's disease (AD). We analyzed 3-Tesla diffusion-weighted images from 202 patients scanned by the Alzheimer's Disease Neuroimaging Initiative – 50 healthy controls, 72 with early- and 38 with late-stage mild cognitive impairment (eMCI/lMCI) and 42 with AD. Using whole-brain tractography, we reconstructed structural connectivity networks representing connections between pairs of cortical regions. We examined, for the first time in this context, the network's Laplacian matrix and its Fiedler value, describing the network's algebraic connectivity, and the Fiedler vector, used to partition a graph. We assessed algebraic connectivity and four additional supporting metrics, revealing a decrease in network robustness and increasing disarray among nodes as dementia progressed. Network components became more disconnected and segregated, and their modularity increased. These measures are sensitive to diagnostic group differences, and may help understand the complex changes in AD. PMID:26640830

  7. Enriched environment decreases microglia and brain macrophages inflammatory phenotypes through adiponectin-dependent mechanisms: Relevance to depressive-like behavior.

    Science.gov (United States)

    Chabry, Joëlle; Nicolas, Sarah; Cazareth, Julie; Murris, Emilie; Guyon, Alice; Glaichenhaus, Nicolas; Heurteaux, Catherine; Petit-Paitel, Agnès

    2015-11-01

    Regulation of neuroinflammation by glial cells plays a major role in the pathophysiology of major depression. While astrocyte involvement has been well described, the role of microglia is still elusive. Recently, we have shown that Adiponectin (ApN) plays a crucial role in the anxiolytic/antidepressant neurogenesis-independent effects of enriched environment (EE) in mice; however its mechanisms of action within the brain remain unknown. Here, we show that in a murine model of depression induced by chronic corticosterone administration, the hippocampus and the hypothalamus display increased levels of inflammatory cytokines mRNA, which is reversed by EE housing. By combining flow cytometry, cell sorting and q-PCR, we show that microglia from depressive-like mice adopt a pro-inflammatory phenotype characterized by higher expression levels of IL-1β, IL-6, TNF-α and IκB-α mRNAs. EE housing blocks pro-inflammatory cytokine gene induction and promotes arginase 1 mRNA expression in brain-sorted microglia, indicating that EE favors an anti-inflammatory activation state. We show that microglia and brain-macrophages from corticosterone-treated mice adopt differential expression profiles for CCR2, MHC class II and IL-4recα surface markers depending on whether the mice are kept in standard environment or EE. Interestingly, the effects of EE were abolished when cells are isolated from ApN knock-out mouse brains. When injected intra-cerebroventricularly, ApN, whose level is specifically increased in cerebrospinal fluid of depressive mice raised in EE, rescues microglia phenotype, reduces pro-inflammatory cytokine production by microglia and blocks depressive-like behavior in corticosterone-treated mice. Our data suggest that EE-induced ApN increase within the brain regulates microglia and brain macrophages phenotype and activation state, thus reducing neuroinflammation and depressive-like behaviors in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Brain Metabolism Alterations Induced by Pregnancy Swimming Decreases Neurological Impairments Following Neonatal Hypoxia-Ischemia in Very Immature Rats

    Directory of Open Access Journals (Sweden)

    Eduardo F. Sanches

    2018-06-01

    Full Text Available Introduction: Prematurity, through brain injury and altered development is a major cause of neurological impairments and can result in motor, cognitive and behavioral deficits later in life. Presently, there are no well-established effective therapies for preterm brain injury and the search for new strategies is needed. Intra-uterine environment plays a decisive role in brain maturation and interventions using the gestational window have been shown to influence long-term health in the offspring. In this study, we investigated whether pregnancy swimming can prevent the neurochemical metabolic alterations and damage that result from postnatal hypoxic-ischemic brain injury (HI in very immature rats.Methods: Female pregnant Wistar rats were divided into swimming (SW or sedentary (SE groups. Following a period of adaptation before mating, swimming was performed during the entire gestation. At postnatal day (PND3, rat pups from SW and SE dams had right common carotid artery occluded, followed by systemic hypoxia. At PND4 (24 h after HI, the early neurochemical profile was measured by 1H-magnetic resonance spectroscopy. Astrogliosis, apoptosis and neurotrophins protein expression were assessed in the cortex and hippocampus. From PND45, behavioral testing was performed. Diffusion tensor imaging and neurite orientation dispersion and density imaging were used to evaluate brain microstructure and the levels of proteins were quantified.Results: Pregnancy swimming was able to prevent early metabolic changes induced by HI preserving the energetic balance, decreasing apoptotic cell death and astrogliosis as well as maintaining the levels of neurotrophins. At adult age, swimming preserved brain microstructure and improved the performance in the behavioral tests.Conclusion: Our study points out that swimming during gestation in rats could prevent prematurity related brain damage in progeny with high translational potential and possibly interesting cost

  9. Deep brain stimulation affects conditioned and unconditioned anxiety in different brain areas

    NARCIS (Netherlands)

    van Dijk, A.; Klanker, M.; van Oorschot, N.; Post, R.; Hamelink, R.; Feenstra, M. G. P.; Denys, D.

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has proven to be an effective treatment for therapy refractory obsessive compulsive disorder. Clinical observations show that anxiety symptoms decrease rapidly following DBS. As in clinical studies different regions are targeted, it is of

  10. SPECT brain perfusion imaging in mild traumatic brain injury

    International Nuclear Information System (INIS)

    Li Juan; Liu Baojun; Zhao Feng; He Lirong; Xia Yucheng

    2003-01-01

    Objective: To study the clinical value of SPECT brain perfusion imaging after mild traumatic brain injury and to evaluate the mechanism of brain blood flow changes in the brain traumatic symptoms. Methods: SPECT 99 Tc m -ethylene cysteinate dimer (ECD) brain perfusion imaging was performed on 39 patients with normal consciousness and normal computed tomography. The study was performed on 23 patients within 3 months after the accidental injury and on 16 patients at more than 3 months post-injury. The cerebellum was used as the reference site (100% maximum value). Any decrease in cerebral perfusion in cortex or basal ganglia to below 70%, or even to below 50% in the medial temporal lobe, compared to the cerebellar reference was considered abnormal. Results: The results of 23 patients (59%) were abnormal. Among them, 20 patients showed 74 focal lesions with an average of 3.7 per patient (15 studies performed within 3 months and 8 studies performed more than 3 months after injury). The remaining 3 showed diffuse hypoperfusion (two at the early stage and one at more than 3 months after the injury). The 13 abnormal studies performed at the early stage showed 58 lesions (average, 4.5 per patient), whereas there was a reduction to an average of 2.3 per patient in the 7 patients (total 16 lesions) at more than 3 months post-injury. In the 20 patients with focal lesions, mainly the following regions were involved: frontal lobes 43.2% (32/74), basal ganglia 24.3% (18/74) and temporal lobes 17.6% (13/74). Conclusions: 1) SPECT brain perfusion imaging is more sensitive than computed tomography in detecting brain lesions of mild traumatic brain injury. 2) SPECT brain perfusion imaging is more sensitive at early stage than at late stage after injury. 3) The most common complaints were headache, dizziness, memory deficit. The patients without loss of consciousness may present brain hypoperfusion, too. 4) The changes may explain a neurological component of the patient symptoms in

  11. Image quality and radiation dose of brain computed tomography in children: effects of decreasing tube voltage from 120 kVp to 80 kVp

    International Nuclear Information System (INIS)

    Park, Ji Eun; Choi, Young Hun; Cheon, Jung-Eun; Kim, Woo Sun; Kim, In-One; Cho, Hyun Suk; Ryu, Young Jin; Kim, Yu Jin

    2017-01-01

    Computed tomography (CT) has generated public concern associated with radiation exposure, especially for children. Lowering the tube voltage is one strategy to reduce radiation dose. To assess the image quality and radiation dose of non-enhanced brain CT scans acquired at 80 kilo-voltage peak (kVp) compared to those at 120 kVp in children. Thirty children who had undergone both 80- and 120-kVp non-enhanced brain CT were enrolled. For quantitative analysis, the mean attenuation of white and gray matter, attenuation difference, noise, signal-to-noise ratio, contrast-to-noise ratio and posterior fossa artifact index were measured. For qualitative analysis, noise, gray-white matter differentiation, artifact and overall image quality were scored. Radiation doses were evaluated by CT dose index, dose-length product and effective dose. The mean attenuations of gray and white matter and contrast-to-noise ratio were significantly increased at 80 kVp, while parameters related to image noise, i.e. noise, signal-to-noise ratio and posterior fossa artifact index were higher at 80 kVp than at 120 kVp. In qualitative analysis, 80-kVp images showed improved gray-white differentiation but more artifacts compared to 120-kVp images. Subjective image noise and overall image quality scores were similar between the two scans. Radiation dose parameters were significantly lower at 80 kVp than at 120 kVp. In pediatric non-enhanced brain CT scans, a decrease in tube voltage from 120 kVp to 80 kVp resulted in improved gray-white matter contrast, comparable image quality and decreased radiation dose. (orig.)

  12. Image quality and radiation dose of brain computed tomography in children: effects of decreasing tube voltage from 120 kVp to 80 kVp.

    Science.gov (United States)

    Park, Ji Eun; Choi, Young Hun; Cheon, Jung-Eun; Kim, Woo Sun; Kim, In-One; Cho, Hyun Suk; Ryu, Young Jin; Kim, Yu Jin

    2017-05-01

    Computed tomography (CT) has generated public concern associated with radiation exposure, especially for children. Lowering the tube voltage is one strategy to reduce radiation dose. To assess the image quality and radiation dose of non-enhanced brain CT scans acquired at 80 kilo-voltage peak (kVp) compared to those at 120 kVp in children. Thirty children who had undergone both 80- and 120-kVp non-enhanced brain CT were enrolled. For quantitative analysis, the mean attenuation of white and gray matter, attenuation difference, noise, signal-to-noise ratio, contrast-to-noise ratio and posterior fossa artifact index were measured. For qualitative analysis, noise, gray-white matter differentiation, artifact and overall image quality were scored. Radiation doses were evaluated by CT dose index, dose-length product and effective dose. The mean attenuations of gray and white matter and contrast-to-noise ratio were significantly increased at 80 kVp, while parameters related to image noise, i.e. noise, signal-to-noise ratio and posterior fossa artifact index were higher at 80 kVp than at 120 kVp. In qualitative analysis, 80-kVp images showed improved gray-white differentiation but more artifacts compared to 120-kVp images. Subjective image noise and overall image quality scores were similar between the two scans. Radiation dose parameters were significantly lower at 80 kVp than at 120 kVp. In pediatric non-enhanced brain CT scans, a decrease in tube voltage from 120 kVp to 80 kVp resulted in improved gray-white matter contrast, comparable image quality and decreased radiation dose.

  13. Image quality and radiation dose of brain computed tomography in children: effects of decreasing tube voltage from 120 kVp to 80 kVp

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji Eun [Kyung Hee University Hospital, Department of Radiology, Graduate School, Seoul (Korea, Republic of); Choi, Young Hun [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Cheon, Jung-Eun; Kim, Woo Sun; Kim, In-One [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of); Cho, Hyun Suk; Ryu, Young Jin; Kim, Yu Jin [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of)

    2017-05-15

    Computed tomography (CT) has generated public concern associated with radiation exposure, especially for children. Lowering the tube voltage is one strategy to reduce radiation dose. To assess the image quality and radiation dose of non-enhanced brain CT scans acquired at 80 kilo-voltage peak (kVp) compared to those at 120 kVp in children. Thirty children who had undergone both 80- and 120-kVp non-enhanced brain CT were enrolled. For quantitative analysis, the mean attenuation of white and gray matter, attenuation difference, noise, signal-to-noise ratio, contrast-to-noise ratio and posterior fossa artifact index were measured. For qualitative analysis, noise, gray-white matter differentiation, artifact and overall image quality were scored. Radiation doses were evaluated by CT dose index, dose-length product and effective dose. The mean attenuations of gray and white matter and contrast-to-noise ratio were significantly increased at 80 kVp, while parameters related to image noise, i.e. noise, signal-to-noise ratio and posterior fossa artifact index were higher at 80 kVp than at 120 kVp. In qualitative analysis, 80-kVp images showed improved gray-white differentiation but more artifacts compared to 120-kVp images. Subjective image noise and overall image quality scores were similar between the two scans. Radiation dose parameters were significantly lower at 80 kVp than at 120 kVp. In pediatric non-enhanced brain CT scans, a decrease in tube voltage from 120 kVp to 80 kVp resulted in improved gray-white matter contrast, comparable image quality and decreased radiation dose. (orig.)

  14. Brain functional connectivity and cognition in mild traumatic brain injury

    International Nuclear Information System (INIS)

    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.)

  15. 2-d spectroscopic imaging of brain tumours

    International Nuclear Information System (INIS)

    Ferris, N.J.; Brotchie, P.R.

    2002-01-01

    Full text: This poster illustrates the use of two-dimensional spectroscopic imaging (2-D SI) in the characterisation of brain tumours, and the monitoring of subsequent treatment. After conventional contrast-enhanced MR imaging of patients with known or suspected brain tumours, 2-D SI is performed at a single axial level. The level is chosen to include the maximum volume of abnormal enhancement, or, in non-enhancing lesions. The most extensive T2 signal abnormality. Two different MR systems have been used (Marconi Edge and GE Signa LX); at each site, a PRESS localisation sequence is employed with TE 128-144 ms. Automated software is used to generate spectral arrays, metabolite maps, and metabolite ratio maps from the spectroscopic data. Colour overlays of the maps onto anatomical images are produced using manufacturer software or the Medex imaging data analysis package. High grade gliomas showed choline levels higher than those in apparently normal brain, with decreases in NAA and creatine. Some lesions showed spectral abnormality extending into otherwise normal appearing brain. This was also seen in a case of CNS lymphoma. Lowgrade lesions showed choline levels similar to normal brain, but with decreased NAA. Only a small number of metastases have been studied, but to date no metastasis has shown spectral abnormality beyond the margins suggested by conventional imaging. Follow-up studies generally show spectral heterogeneity. Regions with choline levels higher than those in normal-appearing brain are considered to represent recurrent high-grade tumour. Some regions show choline to be the dominant metabolite, but its level is not greater than that seen in normal brain. These regions are considered suspicious for residual / recurrent tumour when the choline / creatine ratio exceeds 2 (lower ratios may represent treatment effect). 2-D SI improves the initial assessment of brain tumours, and has potential for influencing the radiotherapy treatment strategy. 2-D SI also

  16. Magnetic resonance imaging acquisition techniques intended to decrease movement artefact in paediatric brain imaging: a systematic review

    International Nuclear Information System (INIS)

    Woodfield, Julie; Kealey, Susan

    2015-01-01

    Attaining paediatric brain images of diagnostic quality can be difficult because of young age or neurological impairment. The use of anaesthesia to reduce movement in MRI increases clinical risk and cost, while CT, though faster, exposes children to potentially harmful ionising radiation. MRI acquisition techniques that aim to decrease movement artefact may allow diagnostic paediatric brain imaging without sedation or anaesthesia. We conducted a systematic review to establish the evidence base for ultra-fast sequences and sequences using oversampling of k-space in paediatric brain MR imaging. Techniques were assessed for imaging time, occurrence of movement artefact, the need for sedation, and either image quality or diagnostic accuracy. We identified 24 relevant studies. We found that ultra-fast techniques had shorter imaging acquisition times compared to standard MRI. Techniques using oversampling of k-space required equal or longer imaging times than standard MRI. Both ultra-fast sequences and those using oversampling of k-space reduced movement artefact compared with standard MRI in unsedated children. Assessment of overall diagnostic accuracy was difficult because of the heterogeneous patient populations, imaging indications, and reporting methods of the studies. In children with shunt-treated hydrocephalus there is evidence that ultra-fast MRI is sufficient for the assessment of ventricular size. (orig.)

  17. Magnetic resonance imaging acquisition techniques intended to decrease movement artefact in paediatric brain imaging: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Woodfield, Julie [University of Edinburgh, Child Life and Health, Edinburgh (United Kingdom); Kealey, Susan [Western General Hospital, Department of Neuroradiology, Edinburgh (United Kingdom)

    2015-08-15

    Attaining paediatric brain images of diagnostic quality can be difficult because of young age or neurological impairment. The use of anaesthesia to reduce movement in MRI increases clinical risk and cost, while CT, though faster, exposes children to potentially harmful ionising radiation. MRI acquisition techniques that aim to decrease movement artefact may allow diagnostic paediatric brain imaging without sedation or anaesthesia. We conducted a systematic review to establish the evidence base for ultra-fast sequences and sequences using oversampling of k-space in paediatric brain MR imaging. Techniques were assessed for imaging time, occurrence of movement artefact, the need for sedation, and either image quality or diagnostic accuracy. We identified 24 relevant studies. We found that ultra-fast techniques had shorter imaging acquisition times compared to standard MRI. Techniques using oversampling of k-space required equal or longer imaging times than standard MRI. Both ultra-fast sequences and those using oversampling of k-space reduced movement artefact compared with standard MRI in unsedated children. Assessment of overall diagnostic accuracy was difficult because of the heterogeneous patient populations, imaging indications, and reporting methods of the studies. In children with shunt-treated hydrocephalus there is evidence that ultra-fast MRI is sufficient for the assessment of ventricular size. (orig.)

  18. Impact of playing American professional football on long-term brain function.

    Science.gov (United States)

    Amen, Daniel G; Newberg, Andrew; Thatcher, Robert; Jin, Yi; Wu, Joseph; Keator, David; Willeumier, Kristen

    2011-01-01

    The authors recruited 100 active and former National Football League players, representing 27 teams and all positions. Players underwent a clinical history, brain SPECT imaging, qEEG, and multiple neuropsychological measures, including MicroCog. Relative to a healthy-comparison group, players showed global decreased perfusion, especially in the prefrontal, temporal, parietal, and occipital lobes, and cerebellar regions. Quantitative EEG findings were consistent, showing elevated slow waves in the frontal and temporal regions. Significant decreases from normal values were found in most neuropsychological tests. This is the first large-scale brain-imaging study to demonstrate significant differences consistent with a chronic brain trauma pattern in professional football players.

  19. X-ray sensitive strains of CHO cells show decreased frequency of stable transfection

    International Nuclear Information System (INIS)

    Jeggo, P.; Smith, J.

    1987-01-01

    Six X-ray sensitive (xrs) strains of the Chinese hamster ovary cell line have previously been isolated and shown to have a defect in double strand break rejoining. In this study, these strains have been investigated for their ability to take up and integrate foreign DNA. All the xrs strains investigated so far have shown a decreased frequency of stable transfectants compared to their parent line, in experiments using the plasmid pSV2gpt, which contains the selectable bacterial gene, guanine phosphoribosyl transferase. This decreased frequency is observed over a wide range of DNA concentrations (0.1 to 20 μg DNA) but is more pronounced at higher DNA concentrations. In contrast, these xrs strains show the same level of transfection proficiency as the wild type parent using a transient transfection system with a plasmid containing the bacterial CAT (chloramphenicol acetyl transferase) gene. Since the level of CAT activity does not depend on integration of foreign DNA, this suggests that the xrs strains are able to take up the same amount of DNA as the parent strains, but have a defect in the integration of foreign DNA. Since this integration of foreign DNA probably occurs by non-homologous recombination, this may indicate a role of the xrs gene product in this process

  20. Let-7i attenuates human brain microvascular endothelial cell damage in oxygen glucose deprivation model by decreasing toll-like receptor 4 expression.

    Science.gov (United States)

    Xiang, Wei; Tian, Canhui; Peng, Shunli; Zhou, Liang; Pan, Suyue; Deng, Zhen

    2017-11-04

    The let-7 family of microRNAs (miRNAs) plays an important role on endothelial cell function. However, there have been few studies on their role under ischemic conditions. In this study, we demonstrate that let-7i, belonging to the let-7 family, rescues human brain microvascular endothelial cells (HBMECs) in an oxygen-glucose deprivation (OGD) model. Our data show that the expression of let-7 family miRNAs was downregulated after OGD. Overexpression of let-7i significantly alleviated cell death and improved survival of OGD-treated HBMECs. Let-7i also protected permeability in an in vitro blood brain barrier (BBB) model. Further, let-7i downregulated the expression of toll-like receptor 4 (TLR4), an inflammation trigger. Moreover, overexpression of let-7i decreased matrix metallopeptidase 9 (MMP9) and inducible nitric oxide synthase (iNOS) expression under OGD. Upon silencing TLR4 expression in HBMECs, the anti-inflammatory effect of let-7i was abolished. Our research suggests that let-7i promotes OGD-induced inflammation via downregulating TLR4 expression. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Decreased electrophysiological activity represents the conscious state of emptiness in meditation

    Science.gov (United States)

    Hinterberger, Thilo; Schmidt, Stephanie; Kamei, Tsutomu; Walach, Harald

    2014-01-01

    Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG) of 50 participants of various meditation proficiencies was measured during distinct and idiosyncratic meditative tasks. The tasks comprised a wakeful “thoughtless emptiness (TE),” a “focused attention,” and an “open monitoring” task asking for mindful presence in the moment and in the environment without attachment to distracting thoughts. Our analysis mainly focused on 30 highly experienced meditators with at least 5 years and 1000 h of meditation experience. Spectral EEG power comparisons of the TE state with the resting state or other forms of meditation showed decreased activities in specific frequency bands. In contrast to a focused attention task the TE task showed significant central and parietal gamma decreases (p meditation practice did not present those differences significantly. Our findings indicate that a conscious state of TE reached by experienced meditators is characterized by reduced high-frequency brain processing with simultaneous reduction of the low frequencies. This suggests that such a state of meditative conscious awareness might be different from higher cognitive and mentally focused states but also from states of sleep and drowsiness. PMID:24596562

  2. Metallothionein-I overexpression alters brain inflammation and stimulates brain repair in transgenic mice with astrocyte-targeted interleukin-6 expression

    DEFF Research Database (Denmark)

    Penkowa, Milena; Camats, Jordi; Giralt, Mercedes

    2003-01-01

    injury, such as a cryolesion, demonstrate a neuroprotective role of IL-6. Thus, the GFAP-IL-6 mice showed faster tissue repair and decreased oxidative stress and apoptosis compared with control litter-mate mice. The neuroprotective factors metallothionein-I+II (MT-I+II) were upregulated by the cryolesion...... the inflammatory response, decreased oxidative stress and apoptosis significantly, and increased brain tissue repair in comparison with either GFAP-IL-6 or control litter-mate mice. Overall, the results demonstrate that brain MT-I+II proteins are fundamental neuroprotective factors....

  3. 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)

  4. MicroRNAs show mutually exclusive expression patterns in the brain of adult male rats

    DEFF Research Database (Denmark)

    Olsen, Line; Klausen, Mikkel; Helboe, Lone

    2009-01-01

    BACKGROUND: The brain is a major site of microRNA (miRNA) gene expression, but the spatial expression patterns of miRNAs within the brain have not yet been fully covered. METHODOLOGY/PRINCIPAL FINDINGS: We have characterized the regional expression profiles of miRNAs in five distinct regions...... of the adult rat brain: amygdala, cerebellum, hippocampus, hypothalamus and substantia nigra. Microarray profiling uncovered 48 miRNAs displaying more than three-fold enrichment between two or more brain regions. Notably, we found reciprocal expression profiles for a subset of the miRNAs predominantly found...... (> ten times) in either the cerebellum (miR-206 and miR-497) or the forebrain regions (miR-132, miR-212, miR-221 and miR-222). CONCLUSIONS/SIGNIFICANCE: The results indicate that some miRNAs could be important for area-specific functions in the brain. Our data, combined with previous studies in mice...

  5. Spontaneous Brain Activity Did Not Show the Effect of Violent Video Games on Aggression: A Resting-State fMRI Study

    Science.gov (United States)

    Pan, Wei; Gao, Xuemei; Shi, Shuo; Liu, Fuqu; Li, Chao

    2018-01-01

    A great many of empirical researches have proved that longtime exposure to violent video game can lead to a series of negative effects. Although research has focused on the neural basis of the correlation between violent video game and aggression, little is known whether the spontaneous brain activity is associated with violent video game exposure. To address this question, we measured the spontaneous brain activity using resting-state functional magnetic resonance imaging (fMRI). We used the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) to quantify spontaneous brain activity. The results showed there is no significant difference in ALFF, or fALFF, between violent video game group and the control part, indicating that long time exposure to violent video games won’t significantly influence spontaneous brain activity, especially the core brain regions such as execution control, moral judgment and short-term memory. This implies the adverse impact of violent video games is exaggerated. PMID:29375416

  6. Spontaneous Brain Activity Did Not Show the Effect of Violent Video Games on Aggression: A Resting-State fMRI Study.

    Science.gov (United States)

    Pan, Wei; Gao, Xuemei; Shi, Shuo; Liu, Fuqu; Li, Chao

    2017-01-01

    A great many of empirical researches have proved that longtime exposure to violent video game can lead to a series of negative effects. Although research has focused on the neural basis of the correlation between violent video game and aggression, little is known whether the spontaneous brain activity is associated with violent video game exposure. To address this question, we measured the spontaneous brain activity using resting-state functional magnetic resonance imaging (fMRI). We used the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) to quantify spontaneous brain activity. The results showed there is no significant difference in ALFF, or fALFF, between violent video game group and the control part, indicating that long time exposure to violent video games won't significantly influence spontaneous brain activity, especially the core brain regions such as execution control, moral judgment and short-term memory. This implies the adverse impact of violent video games is exaggerated.

  7. Spontaneous Brain Activity Did Not Show the Effect of Violent Video Games on Aggression: A Resting-State fMRI Study

    Directory of Open Access Journals (Sweden)

    Wei Pan

    2018-01-01

    Full Text Available A great many of empirical researches have proved that longtime exposure to violent video game can lead to a series of negative effects. Although research has focused on the neural basis of the correlation between violent video game and aggression, little is known whether the spontaneous brain activity is associated with violent video game exposure. To address this question, we measured the spontaneous brain activity using resting-state functional magnetic resonance imaging (fMRI. We used the amplitude of low-frequency fluctuations (ALFF and fractional ALFF (fALFF to quantify spontaneous brain activity. The results showed there is no significant difference in ALFF, or fALFF, between violent video game group and the control part, indicating that long time exposure to violent video games won’t significantly influence spontaneous brain activity, especially the core brain regions such as execution control, moral judgment and short-term memory. This implies the adverse impact of violent video games is exaggerated.

  8. Ketamine alters behavior and decreases BDNF levels in the rat brain as a function of time after drug administration

    Directory of Open Access Journals (Sweden)

    Daiane B. Fraga

    2013-09-01

    Full Text Available Objective: To evaluate behavioral changes and brain-derived neurotrophic factor (BDNF levels in rats subjected to ketamine administration (25 mg/kg for 7 days. Method: Behavioral evaluation was undertaken at 1 and 6 hours after the last injection. Results: We observed hyperlocomotion 1 hour after the last injection and a decrease in locomotion after 6 hours. Immobility time was decreased and climbing time was increased 6 hours after the last injection. BDNF levels were decreased in the prefrontal cortex and amygdala when rats were killed 6 hours after the last injection, compared to the saline group and to rats killed 1 hour after the last injection. BDNF levels in the striatum were decreased in rats killed 6 hours after the last ketamine injection, and BDNF levels in the hippocampus were decreased in the groups that were killed 1 and 6 hours after the last injection. Conclusion: These results suggest that the effects of ketamine on behavior and BDNF levels are related to the time at which they were evaluated after administration of the drug.

  9. Measurement of P-31 MR relaxation times and concentrations in human brain and brain tumors

    International Nuclear Information System (INIS)

    Roth, K.; Naruse, S.; Hubesch, B.; Gober, I.; Lawry, T.; Boska, M.; Matson, G.B.; Weiner, M.W.

    1987-01-01

    Measurements of high-energy phosphates and pH were made in human brain and brain tumors using P-31 MR imaging. Using a Philips Gyroscan 1.5-T MRMRS, MR images were used to select a cuboidal volume of interest and P-31 MR spectra were obtained from that volume using the ISIS technique. An external quantitation standard was used. T 1 s were measured by inversion recovery. Quantitative values for metabolites were calculated using B 1 field plot of the head coil. The results for normal brain phosphates are as follows; adenosine triphosphate, 2.2 mM; phosphocreatin, 5.3 mM; inorganic phosphate, 1.6 mM. Preliminary studies with human brain tumors show a decrease of all phosphate compounds. These experiments are the first to quantitate metabolites in human brain

  10. Decision-making deficit of a patient with axonal damage after traumatic brain injury.

    Science.gov (United States)

    Yasuno, Fumihiko; Matsuoka, Kiwamu; Kitamura, Soichiro; Kiuchi, Kuniaki; Kosaka, Jun; Okada, Koji; Tanaka, Syohei; Shinkai, Takayuki; Taoka, Toshiaki; Kishimoto, Toshifumi

    2014-02-01

    Patients with traumatic brain injury (TBI) were reported to have difficulty making advantageous decisions, but the underlying deficits of the network of brain areas involved in this process were not directly examined. We report a patient with TBI who demonstrated problematic behavior in situations of risk and complexity after cerebral injury from a traffic accident. The Iowa gambling task (IGT) was used to reveal his deficits in the decision-making process. To examine underlying deficits of the network of brain areas, we examined T1-weighted structural MRI, diffusion tensor imaging (DTI) and Tc-ECD SPECT in this patient. The patient showed abnormality in IGT. DTI-MRI results showed a significant decrease in fractional anisotropy (FA) in the fasciculus between the brain stem and cortical regions via the thalamus. He showed significant decrease in gray matter volumes in the bilateral insular cortex, hypothalamus, and posterior cingulate cortex, possibly reflecting Wallerian degeneration secondary to the fasciculus abnormalities. SPECT showed significant blood flow decrease in the broad cortical areas including the ventromedial prefrontal cortex (VM). Our study showed that the patient had dysfunctional decision-making process. Microstructural abnormality in the fasciculus, likely from the traffic accident, caused reduced afferent feedback to the brain, resulting in less efficient decision-making. Our findings support the somatic-marker hypothesis (SMH), where somatic feedback to the brain influences the decision-making process. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Rapid decrease in brain enkephalin content after low-dose whole-body X-irradiation of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Miyachi, Yukihisa (Central Research Inst. of Electric Power Industry, Komae, Tokyo (Japan). Komae Research Lab.); Ogawa, Norio; Mori, Akitane

    1992-03-01

    Methionine-eckephalin (ME) contents in the hypothalamus and other rat brain structures were measured immediately after 10 or 20 cGy whole-body X-irradiation. The ME contents of homogenates of the striatum, hypothalamus, midbrain + thalamus, hindbrain and pituitary were assayed radioimmunologically with {sup 125}I. The contents of all the structure, except the pituitary, decreased significantly after 20 cGy irradiation. The reduction in the hypothalamus was transient, ME content gradually recovering with time. These results suggest that the central nervous system of mammals is one of the most radiosensitive organs as judged by changes in stress-induced mediators such as ME. (author).

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Analysis of a human brain transcriptome map

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.)

  15. Decreased spontaneous activity in AMPK alpha 2 muscle specific kinase dead mice is not caused by changes in brain dopamine metabolism

    DEFF Research Database (Denmark)

    Møller, Lisbeth Liliendal Valbjørn; Sylow, Lykke; Gøtzsche, Casper René

    2016-01-01

    was tested in an open field test. Furthermore, we investigated maximal running capacity and voluntary running over a period of 19 days. AMPK α2 KD mice ran 30% less in daily distance compared to WT. Furthermore, AMPK α2 KD mice showed significantly decreased locomotor activity in the open field test compared...... through alterations of the brain dopamine levels specifically in the striatal region. To test this hypothesis, transgenic mice overexpressing an inactivatable dominant negative α2 AMPK construct (AMPK α2 KD) in muscles and littermate wildtype (WT) mice were tested. AMPK α2 KD mice have impaired running...... capacity and display reduced voluntary wheel running activity. Striatal content of dopamine and its metabolites were measured under basal physiological conditions and after cocaine-induced dopamine efflux from the ventral striatum by in vivo microdialysis. Moreover, cocaine-induced locomotor activity...

  16. Early tracheostomy in severe traumatic brain injury: evidence for decreased mechanical ventilation and increased hospital mortality

    Science.gov (United States)

    Dunham, C Michael; Cutrona, Anthony F; Gruber, Brian S; Calderon, Javier E; Ransom, Kenneth J; Flowers, Laurie L

    2014-01-01

    Objective: In the past, the authors performed a comprehensive literature review to identify all randomized controlled trials assessing the impact of early tracheostomy on severe brain injury outcomes. The search produced only two trials, one by Sugerman and another by Bouderka. Subjects and methods: The current authors initiated an Institutional Review Board-approved severe brain injury randomized trial to evaluate the impact of early tracheostomy on ventilator-associated pneumonia rates, intensive care unit (ICU)/ventilator days, and hospital mortality. Current study results were compared with the other randomized trials and a meta-analysis was performed. Results: Early tracheostomy pneumonia rates were Sugerman-48.6%, Bouderka-58.1%, and current study-46.7%. No early tracheostomy pneumonia rates were Sugerman-53.1%, Bouderka-61.3%, and current study-44.4%. Pneumonia rate meta-analysis showed no difference for early tracheostomy and no early tracheostomy (OR 0.89; p = 0.71). Early tracheostomy ICU/ventilator days were Sugerman-16 ± 5.9, Bouderka-14.5 ± 7.3, and current study-14.1 ± 5.7. No early tracheostomy ICU/ventilator days were Sugerman-19 ± 11.3, Bouderka-17.5 ± 10.6, and current study-17 ± 5.4. ICU/ventilator day meta-analysis showed 2.9 fewer days with early tracheostomy (p = 0.02). Early tracheostomy mortality rates were Sugerman-14.3%, Bouderka-38.7%, and current study-0%. No early tracheostomy mortality rates were Sugerman-3.2%, Bouderka-22.6%, and current study-0%. Randomized trial mortality rate meta-analysis showed a higher rate for early tracheostomy (OR 2.68; p = 0.05). Because the randomized trials were small, a literature assessment was undertaken to find all retrospective studies describing the association of early tracheostomy on severe brain injury hospital mortality. The review produced five retrospective studies, with a total of 3,356 patients. Retrospective study mortality rate meta-analysis demonstrated a larger mortality for early

  17. Prion protein is decreased in Alzheimer's brain and inversely correlates with BACE1 activity, amyloid-β levels and Braak stage.

    Directory of Open Access Journals (Sweden)

    Isobel J Whitehouse

    Full Text Available The cellular prion protein (PrP(C has been implicated in the development of Alzheimer's disease (AD. PrP(C decreases amyloid-β (Aβ production, which is involved in AD pathogenesis, by inhibiting β-secretase (BACE1 activity. Contactin 5 (CNTN5 has also been implicated in the development of AD by a genome-wide association study. Here we measured PrP(C and CNTN5 in frontal cortex samples from 24 sporadic AD and 24 age-matched control brains and correlated the expression of these proteins with markers of AD. PrP(C was decreased in sporadic AD compared to controls (by 49%, p = 0.014 but there was no difference in CNTN5 between sporadic AD and controls (p = 0.217. PrP(C significantly inversely correlated with BACE1 activity (rs = -0.358, p = 0.006, Aβ load (rs = -0.456, p = 0.001, soluble Aβ (rs = -0.283, p = 0.026 and insoluble Aβ (rs = -0.353, p = 0.007 and PrP(C also significantly inversely correlated with the stage of disease, as indicated by Braak tangle stage (rs = -0.377, p = 0.007. CNTN5 did not correlate with Aβ load (rs = 0.040, p = 0.393, soluble Aβ (rs = 0.113, p = 0.223 or insoluble Aβ (rs = 0.169, p = 0.125. PrP(C was also measured in frontal cortex samples from 9 Down's syndrome (DS and 8 age-matched control brains. In contrast to sporadic AD, there was no difference in PrP(C in the DS brains compared to controls (p = 0.625. These data are consistent with a role for PrP(C in regulating Aβ production and indicate that brain PrP(C level may be important in influencing the onset and progression of sporadic AD.

  18. Decreased dopamine activity predicts relapse in methamphetamine abusers

    Energy Technology Data Exchange (ETDEWEB)

    Wang G. J.; Wang, G.-J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

    2011-01-20

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

  19. Decreased dopamine activity predicts relapse in methamphetamine abusers

    International Nuclear Information System (INIS)

    Wang, G.J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

    2011-01-01

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and ( 11 C)raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

  20. Neuromolecular Imaging Shows Temporal Synchrony Patterns between Serotonin and Movement within Neuronal Motor Circuits in the Brain

    Directory of Open Access Journals (Sweden)

    Patricia A. Broderick

    2013-06-01

    Full Text Available The present discourse links the electrical and chemical properties of the brain with neurotransmitters and movement behaviors to further elucidate strategies to diagnose and treat brain disease. Neuromolecular imaging (NMI, based on electrochemical principles, is used to detect serotonin in nerve terminals (dorsal and ventral striata and somatodendrites (ventral tegmentum of reward/motor mesocorticolimbic and nigrostriatal brain circuits. Neuronal release of serotonin is detected at the same time and in the same animal, freely moving and unrestrained, while open-field behaviors are monitored via infrared photobeams. The purpose is to emphasize the unique ability of NMI and the BRODERICK PROBE® biosensors to empirically image a pattern of temporal synchrony, previously reported, for example, in Aplysia using central pattern generators (CPGs, serotonin and cerebral peptide-2. Temporal synchrony is reviewed within the context of the literature on central pattern generators, neurotransmitters and movement disorders. Specifically, temporal synchrony data are derived from studies on psychostimulant behavior with and without cocaine while at the same time and continuously, serotonin release in motor neurons within basal ganglia, is detected. The results show that temporal synchrony between the neurotransmitter, serotonin and natural movement occurs when the brain is NOT injured via, e.g., trauma, addictive drugs or psychiatric illness. In striking contrast, in the case of serotonin and cocaine-induced psychostimulant behavior, a different form of synchrony and also asynchrony can occur. Thus, the known dysfunctional movement behavior produced by cocaine may well be related to the loss of temporal synchrony, the loss of the ability to match serotonin in brain with motor activity. The empirical study of temporal synchrony patterns in humans and animals may be more relevant to the dynamics of motor circuits and movement behaviors than are studies of

  1. Neuromolecular Imaging Shows Temporal Synchrony Patterns between Serotonin and Movement within Neuronal Motor Circuits in the Brain.

    Science.gov (United States)

    Broderick, Patricia A

    2013-06-21

    The present discourse links the electrical and chemical properties of the brain with neurotransmitters and movement behaviors to further elucidate strategies to diagnose and treat brain disease. Neuromolecular imaging (NMI), based on electrochemical principles, is used to detect serotonin in nerve terminals (dorsal and ventral striata) and somatodendrites (ventral tegmentum) of reward/motor mesocorticolimbic and nigrostriatal brain circuits. Neuronal release of serotonin is detected at the same time and in the same animal, freely moving and unrestrained, while open-field behaviors are monitored via infrared photobeams. The purpose is to emphasize the unique ability of NMI and the BRODERICK PROBE® biosensors to empirically image a pattern of temporal synchrony, previously reported, for example, in Aplysia using central pattern generators (CPGs), serotonin and cerebral peptide-2. Temporal synchrony is reviewed within the context of the literature on central pattern generators, neurotransmitters and movement disorders. Specifically, temporal synchrony data are derived from studies on psychostimulant behavior with and without cocaine while at the same time and continuously, serotonin release in motor neurons within basal ganglia, is detected. The results show that temporal synchrony between the neurotransmitter, serotonin and natural movement occurs when the brain is NOT injured via, e.g., trauma, addictive drugs or psychiatric illness. In striking contrast, in the case of serotonin and cocaine-induced psychostimulant behavior, a different form of synchrony and also asynchrony can occur. Thus, the known dysfunctional movement behavior produced by cocaine may well be related to the loss of temporal synchrony, the loss of the ability to match serotonin in brain with motor activity. The empirical study of temporal synchrony patterns in humans and animals may be more relevant to the dynamics of motor circuits and movement behaviors than are studies of static parameters

  2. Excessive users of violent video games do not show emotional desensitization: an fMRI study.

    Science.gov (United States)

    Szycik, Gregor R; Mohammadi, Bahram; Hake, Maria; Kneer, Jonas; Samii, Amir; Münte, Thomas F; Te Wildt, Bert T

    2017-06-01

    Playing violent video games have been linked to long-term emotional desensitization. We hypothesized that desensitization effects in excessive users of violent video games should lead to decreased brain activations to highly salient emotional pictures in emotional sensitivity brain regions. Twenty-eight male adult subjects showing excessive long-term use of violent video games and age and education matched control participants were examined in two experiments using standardized emotional pictures of positive, negative and neutral valence. No group differences were revealed even at reduced statistical thresholds which speaks against desensitization of emotion sensitive brain regions as a result of excessive use of violent video games.

  3. Distraction decreases prefrontal oxygenation: A NIRS study.

    Science.gov (United States)

    Ozawa, Sachiyo; Hiraki, Kazuo

    2017-04-01

    When near-infrared spectroscopy (NIRS) is used to measure emotion-related cerebral blood flow (CBF) changes in the prefrontal cortex regions, the functional distinction of CBF changes is often difficult because NIRS is unable to measure neural activity in deeper brain regions that play major roles in emotional processing. The CBF changes could represent cognitive control of emotion and emotional responses to emotional materials. Supposing that emotion-related CBF changes in the prefrontal cortex regions during distraction are emotional responses, we examined whether oxygenated hemoglobin (oxyHb) decreases. Attention-demanding tasks cause blood flow decreases, and we thus compared the effects of visually paced tapping with different tempos, on distraction. The results showed that the oxyHb level induced by emotional stimulation decreased with fast-tempo tapping significantly more than slow-tempo tapping in ventral medial prefrontal cortex regions. Moreover, a Global-Local task following tapping showed significantly greater local-minus-global response time (RT) difference scores in the fast- and mid-tempo condition compared with those in the slow-tempo, suggesting an increased attentional focus, and decreased negative emotion. The overall findings indicate that oxyHb changes in a relatively long distraction task, as measured by NIRS, are associated with emotional responses, and oxyHb can be decreased by successfully performing attention-demanding distraction tasks. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Sequential observations of brain edema with proton magnetic resonance imaging and spectroscopy

    International Nuclear Information System (INIS)

    Kamada, Kyousuke

    1996-01-01

    The purpose of this study was to assess the relationship between morphological and metabolic changes in brain edema using proton magnetic resonance systems. The serial changes during the first 24 hours in the cold-injury trauma rat brain model were investigated by proton magnetic resonance imaging ( 1 H MRI) and high-resolution proton MR spectroscopy ( 1 H MRS). We also analyzed the efficacy of AVS 1,2-bis (nicotinamide)-propane which can scavenge free radicals to the edema in this experiment. The edema was developing extensively via the corpus callosum in ipsi- and contralateral hemispheres as shown by gradually increased signal intensity on 1 H MRI. 1 H MRS initially showed accumulation of acetate and lactate, and transient increasing of glutamine. After 24 hours, the increased glutamine decreased below the control, alanine increased, and N-acetyl aspartate decreased with the edema development. AVS-treatment significantly suppressed edema development, increases of lactate and alanine and decreases of N-acetyl aspartate. We suggest that the cold-induced lesion contains anaerobic glycolysis deterioration and results in severe brain tissue breakdown. AVS is proved valuable for the treatment of this edema lesion. Clinical 1 H MRS showed prolonged lactate elevation and significant decreases of other metabolites in human ischemic stroke edema. In peritumoral edema, decreased N-acetyl aspartate gradually improved, and slightly elevated lactate disappeared after tumor removal. 1 H MRS feasibly characterizes the ischemic and peritumoral edema and makes a quantitative analysis in human brain metabolism. We believe the combined 1 H MRI and MRS study is a practical method to monitor the brain conditions and will make it easy and possible to find new therapeutic agents to some brain disorders. (author)

  5. Yeast-2-Hybrid data file showing progranulin interactions in human fetal brain and bone marrow libraries.

    Science.gov (United States)

    Tegeder, Irmgard

    2016-12-01

    Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech). This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016) [1].

  6. Examination of human brain tumors in situ with image-localized H-1 MR spectroscopy

    International Nuclear Information System (INIS)

    Luyten, P.R.; Segebarth, C.; Baleriaux, D.; Den Hollander, J.A.

    1987-01-01

    Human brain tumors were examined in situ by combined imaging and H-1 MR spectroscopy at 1.5 T. Water-suppressed localized H-1 MR spectra obtained from the brains of normal volunteers show resonances from lactate, N-acetyl aspartate (NAA), creatine, and choline. Several patients suffering from different brain tumors were examined, showing spectral changes in the region of 0.5-1.5 ppm; spectral editing showed that these changes were not due to lactic acid, but to lipid signals. The NAA signal was decreased in the tumors as compared with normal brain. This study shows that H-1 MR spectroscopy can monitor submillimolar changes in chemical composition of human brain tumors in situ

  7. The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Frentzel Stefan

    2010-06-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD. In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD. Results Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels. Conclusions Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.

  8. Preliminary application of voxel-based morphometry technique on brain changes in neuromyelitis

    International Nuclear Information System (INIS)

    Xiao Hui; Ma Lin; Chen Ziqian; Lou Xin; Chen Zhiye

    2011-01-01

    Objective: To investigate the changes of brain volumes in neuromyelitis optica (NMO) patients using voxel-based morphometry (VBM) method, and preliminarily explore the pattern of cerebral anatomical impairment. Methods: Twenty-three clinically defined NMO patients and 15 gender and age matched healthy volunteers underwent 3-dimensional (3D) fast spoiled gradient echo (FSPGR) sequence scanning on 3.0 Tesla MR system. Raw data was processed and analyzed using statistical parametric mapping (SPM) 5. Whole brain volumes included grey matter volume (GMV), white matter volume (WMV), total intracranial volume (TIV), grey matter fraction (GMF), white matter fraction (WMF), brain tissue fraction (BTF) and regional brain volumes between the two groups were compared by independent samples t-test and an Pearson were performed to compare the regional brain volumes and the ages. Results: GMV of NMO group [(610.2±55.0) ml] was significantly decreased comparing to healthy control group [(657.2±36.3) ml] (t=-2.915, P<0.05). The age of NMO patients [(40±9) years old] showed negative correlation with GMF [(42.5±2.6) %] (r=-0.673, P<0.05). Regional brain volume analysis showed decreased GMV in left insula and bilateral posterior cingutates in NMO patients, while decreased WMV was found in left frontal and left parietal white matter. Conclusion: VBM could detect brain volume changes sensitively. Total grey matter volume in NMO patients was decreased comparing to HC group. Regional grey matter atrophy in NMO patients occurred in left insular and bilateral posterior cingutates, regional white matter atrophy occurred in left frontal and left parietal lobe. (authors)

  9. Brain Perfusion SPECT Imaging in Sturge - Weber Syndrome : Comparison with MR Imaging

    International Nuclear Information System (INIS)

    Ryu, Jin Sook; Choi, Yun Young; Moon, Dae Hyuk; Yang, Seoung Oh; Ko, Tae Sung; Yoo, Shi Joon; Lee, Hee Kyung

    1996-01-01

    The purpose of this study was evaluate the characteristic perfusion changes in patients with Sturge-Weber syndrome by comparison of the findings of brain MR images and perfusion SPECT images. 99m Tc-HMPAO or 99m Tc-ECD interictal brain SPECTs were performed on 5 pediatric patients with Struge-Weber syndrome within 2 weeks after MR imaging. Brain SPECTs of three patients without calcification showed diminished perfusion in the affected area on MR image. A 3 month-old patient without brain atrophy or calcification demonstrated paradoxical hyperperfusion in the affected hemisphere, and follow-up perfusion SPECT revealed decreased perfusion in the same area. The other patient with advanced calcified lesion and atrophy on MR image showed diffusely decreased perfusion in the affected hemisphere, but a focal area of increased perfusion was also noted in the ipsilateral temporal lobe on SPECT. In conclusion, brain perfusion of the affected area of Sturge-Weber syndrome patients was usually diminished, but early or advanced patients may show paradoxical diffuse or focal hyperperfusion in the affected hemisphere. Further studies are needed for better understanding of these perfusion changes and pathophysiology of Struge-Weber syndrome.

  10. Initial brain aging

    DEFF Research Database (Denmark)

    Thomsen, Kirsten; Yokota, Takashi; Hasan-Olive, Md Mahdi

    2018-01-01

    Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB(m/m)) and C57Bl/6 (WT......) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB(m/m) hippocampus, but not in CSB(m/m) cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased....... Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSB(m/m) compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event...

  11. Simvastatin decreases steroid production in the H295R cell line and decreases steroids and FSH in female rats

    DEFF Research Database (Denmark)

    Jensen, Anna Guldvang; Hansen, Cecilie Hurup; Weisser, Johan J

    2015-01-01

    .10-0.13μM for SV and from 0.019-0.055μM for SVA. In rats, SV decreased progestagens in ovaries, brain and plasma, and plasma FSH in the M (72.4% decrease) and H group (76.6% decrease). Because progestagens and gonadotropins are major players in fertility, administration of SV might exert negative effects...

  12. [A 53-year-old man with herpes encephalitis showing acceleration of improvement in higher brain function after general anesthesia with sevoflurane: a case report].

    Science.gov (United States)

    Togashi, Naohiko; Kaida, Kenichi; Hongo, Yu; Ogawa, Go; Ishikawa, Yukinobu; Takeda, Katsuhiko; Kamakura, Keiko

    2014-01-01

    We experienced a right-handed 53-year-old man who presented with disturbance of consciousness and fever. Herpes simplex encephalitis (HSE) was diagnosed based on the detection of herpes simplex virus DNA in the cerebrospinal fluid. The administration of acyclovir for 42 days improved his consciousness level. Drowsiness, fever and seizures reappeared 20 days after stopping acyclovir treatment (day 67) and he responded well to vidarabine and methylprednisolone pulse therapy. An assessment of aphasia on day 98 revealed transcortical sensory aphasia. Brain MRI showed lesion in the left temporal lobe, bilateral insular cortexes and bilateral frontal lobe. His higher brain dysfunction continued. On day 156, he underwent hip replacement arthroplasty under general anesthesia sevoflurane. His higher brain dysfunction rapidly improved thereafter. We concluded that the accelerated improvement in our patient's higher brain function was related to the protective effect of sevoflurane. Some reports also show the protective effects of sevoflurane in experimental allergic encephalomyelitis by inhibition of T cell activation. These protective and anti-inflammatory effects may explain the accelerated improvement in higher brain function after general anesthesia.

  13. 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.

  14. [Resting-state functional magnetic resonance study of brain function changes after TIPS operation in patients with liver cirrhosis].

    Science.gov (United States)

    Liu, C; Wang, H B; Yu, Y Q; Wang, M Q; Zhang, G B; Xu, L Y; Wu, J M

    2016-12-20

    Objective: To investigate the brain function changes in cirrhosis patients after transjugular intrahepatic portosystemic shunt (TIPS), resting-state functional MRI (rs-fMRI) performed and fractional amplitude of low frequency fluctuation (fALFF) was analyzed. Methods: From January 2014 to February 2016, a total of 96 cirrhotic patients from invasive technology department and infection department in the First Affiliated Hospital of Anhui Medical University were selected , the blood ammonia data of 96 cirrhotic patients with TIPS operation in four groups were collected after 1, 3, 6 and 12 month, and all subjects performed rs-fMRI scans. The rs-fMRI data processed with DPARSF and SPM12 softwares, whole-brain fALFF values were calculated, and One-Way analysis of variance , multiple comparison analysis and correlation analysis were performed. Results: There were brain regions with significant function changes in four groups patients with TIPS operation after 1, 3, 6 and 12 month, including bilateral superior temporal gyrus, right middle temportal gyrus , right hippocampus, right island of inferior frontal gyrus, left fusiform gyrus, left olfactory cortex, left orbital superior frontal gyrus (all P brain function areas increased in left olfactory cortex, left inferior temporal gyrus, left fusiform gyrus, left orbital middle frontal gyrus, left putamen, left cerebelum, and decreased in left lingual gyrus; patients in the 6-month follow-up showed that brain function areas increased in left middle temportal gyrus, right supramarginal gyrus, right temporal pole, right central operculum, and decreased in left top edge of angular gyrus, left postcentral gyrus; patients in the 12-month follow-up showed that brain function areas increased in right hippocampus, right middle cingulate gyrus, and decreased in right middle temportal gyrus.Compared with patients in the 3-month follow-up, patients in the 6-month follow-up showed that brain function areas increased in left superior

  15. Brain perfusion and cognitive function changes in hypertensive patients

    International Nuclear Information System (INIS)

    Efimova, I.Y.; Efimova, N.Y.; Triss, S.V.; Lishmanov, Y.B.

    2008-01-01

    The aim of our study was to estimate brain perfusion and cognitive function (CF) in patients with arterial hypertension (AH) before and after hypotensive therapy. The study included 15 patients (mean age, 53.0±5.7 years) with previously untreated or ineffectively treated essential hypertension of the second degree. All patients underwent brain single photon emission computed tomography (SPECT) scanning with 99m Tc-hexamethylpropylene amine oxime ( 99m Tc-HMPAO) and comprehensive neuropsychological testing before and after 24 weeks of hypotensive therapy (angiotensin-converting enzyme [ACE] inhibitor or diuretics). The brain perfusion was significantly lower (15-22%) in all regions of AH patients. These patients showed a 25% decrease in attention and psychomotor speed as well as a 14% decrease in mentation. Six months of hypotensive therapy led to an increase in brain perfusion by an average of 7-11% in all brain regions. After treatment these patients demonstrated an average 11-18% improvements in attention and psychomotor speed, as well as an average 10% improvement in abstract mentation. Marked signs of brain hypoperfusion and impaired CF: decrease in attention, slowing psychomotor speed and mentation was found in hypertensive patients even without focal neurological symptomatology. Twenty-four weeks of hypotensive treatment with ACE inhibitors or diuretics had a positive effect on cerebral perfusion and led to CF improvement. (author)

  16. Complex network analysis of resting-state fMRI of the brain.

    Science.gov (United States)

    Anwar, Abdul Rauf; Hashmy, Muhammad Yousaf; Imran, Bilal; Riaz, Muhammad Hussnain; Mehdi, Sabtain Muhammad Muntazir; Muthalib, Makii; Perrey, Stephane; Deuschl, Gunther; Groppa, Sergiu; Muthuraman, Muthuraman

    2016-08-01

    Due to the fact that the brain activity hardly ever diminishes in healthy individuals, analysis of resting state functionality of the brain seems pertinent. Various resting state networks are active inside the idle brain at any time. Based on various neuro-imaging studies, it is understood that various structurally distant regions of the brain could be functionally connected. Regions of the brain, that are functionally connected, during rest constitutes to the resting state network. In the present study, we employed the complex network measures to estimate the presence of community structures within a network. Such estimate is named as modularity. Instead of using a traditional correlation matrix, we used a coherence matrix taken from the causality measure between different nodes. Our results show that in prolonged resting state the modularity starts to decrease. This decrease was observed in all the resting state networks and on both sides of the brain. Our study highlights the usage of coherence matrix instead of correlation matrix for complex network analysis.

  17. The imaging diagnosis of diffuse brain swelling due to severe brain trauma

    International Nuclear Information System (INIS)

    Shen Jianqiang; Hu Jiawang

    2008-01-01

    Objective: To discuss the clinical and pathological characteristics and the imaging types of the diffuse brain swelling due to severe brain trauma. Methods: The clinical data and CT and MR images on 48 cases with diffuse brain swelling due to severe brain trauma were analyzed. Results: Among these 48 cases of the diffuse brain swelling due to severe brain trauma, 33 cases were complicated with brain contusions (including 12 cases brain diffuse axonal injury, 1 case infarct of the right basal ganglion), 31 cases were complicated with hematoma (epidural, subdural or intracerebral), 27 cases were complicated with skull base fracture, and 10 cases were complicated with subarachnoid hematoma. The CT and MR imaging of the diffuse brain swelling included as followed: (1) Symmetrically diffuse brain swelling in both cerebral hemispheres with cerebral ventricles decreased or disappeared, without median line shift. (2)Diffuse brain swelling in one side cerebral hemisphere with cerebral ventricles decreased or disappeared at same side, and median line shift to other side. (3) Subarachnoid hematoma or little subcortex intracerebral hematoma were complicated. (4) The CT value of the cerebral could be equal, lower or higher comparing with normal. Conclusion: The pathological reason of diffuse brain swelling was the brain vessel expanding resulting from hypothalamus and brainstem injured in severe brain trauma. There were four CT and MR imaging findings in diffuse brain swelling. The diffuse brain swelling without hematoma may be caused by ischemical reperfusion injury. (authors)

  18. Resting-state brain activity in adult males who stutter.

    Directory of Open Access Journals (Sweden)

    Yun Xuan

    Full Text Available Although developmental stuttering has been extensively studied with structural and task-based functional magnetic resonance imaging (fMRI, few studies have focused on resting-state brain activity in this disorder. We investigated resting-state brain activity of stuttering subjects by analyzing the amplitude of low-frequency fluctuation (ALFF, region of interest (ROI-based functional connectivity (FC and independent component analysis (ICA-based FC. Forty-four adult males with developmental stuttering and 46 age-matched fluent male controls were scanned using resting-state fMRI. ALFF, ROI-based FCs and ICA-based FCs were compared between male stuttering subjects and fluent controls in a voxel-wise manner. Compared with fluent controls, stuttering subjects showed increased ALFF in left brain areas related to speech motor and auditory functions and bilateral prefrontal cortices related to cognitive control. However, stuttering subjects showed decreased ALFF in the left posterior language reception area and bilateral non-speech motor areas. ROI-based FC analysis revealed decreased FC between the posterior language area involved in the perception and decoding of sensory information and anterior brain area involved in the initiation of speech motor function, as well as increased FC within anterior or posterior speech- and language-associated areas and between the prefrontal areas and default-mode network (DMN in stuttering subjects. ICA showed that stuttering subjects had decreased FC in the DMN and increased FC in the sensorimotor network. Our findings support the concept that stuttering subjects have deficits in multiple functional systems (motor, language, auditory and DMN and in the connections between them.

  19. Resting-State Brain Activity in Adult Males Who Stutter

    Science.gov (United States)

    Zhu, Chaozhe; Wang, Liang; Yan, Qian; Lin, Chunlan; Yu, Chunshui

    2012-01-01

    Although developmental stuttering has been extensively studied with structural and task-based functional magnetic resonance imaging (fMRI), few studies have focused on resting-state brain activity in this disorder. We investigated resting-state brain activity of stuttering subjects by analyzing the amplitude of low-frequency fluctuation (ALFF), region of interest (ROI)-based functional connectivity (FC) and independent component analysis (ICA)-based FC. Forty-four adult males with developmental stuttering and 46 age-matched fluent male controls were scanned using resting-state fMRI. ALFF, ROI-based FCs and ICA-based FCs were compared between male stuttering subjects and fluent controls in a voxel-wise manner. Compared with fluent controls, stuttering subjects showed increased ALFF in left brain areas related to speech motor and auditory functions and bilateral prefrontal cortices related to cognitive control. However, stuttering subjects showed decreased ALFF in the left posterior language reception area and bilateral non-speech motor areas. ROI-based FC analysis revealed decreased FC between the posterior language area involved in the perception and decoding of sensory information and anterior brain area involved in the initiation of speech motor function, as well as increased FC within anterior or posterior speech- and language-associated areas and between the prefrontal areas and default-mode network (DMN) in stuttering subjects. ICA showed that stuttering subjects had decreased FC in the DMN and increased FC in the sensorimotor network. Our findings support the concept that stuttering subjects have deficits in multiple functional systems (motor, language, auditory and DMN) and in the connections between them. PMID:22276215

  20. Yeast-2-Hybrid data file showing progranulin interactions in human fetal brain and bone marrow libraries

    Directory of Open Access Journals (Sweden)

    Irmgard Tegeder

    2016-12-01

    Full Text Available Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech. This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016 [1].

  1. Brain injury and altered brain growth in preterm infants: predictors and prognosis.

    Science.gov (United States)

    Kidokoro, Hiroyuki; Anderson, Peter J; Doyle, Lex W; Woodward, Lianne J; Neil, Jeffrey J; Inder, Terrie E

    2014-08-01

    To define the nature and frequency of brain injury and brain growth impairment in very preterm (VPT) infants by using MRI at term-equivalent age and to relate these findings to perinatal risk factors and 2-year neurodevelopmental outcomes. MRI scans at term-equivalent age from 3 VPT cohorts (n = 325) were reviewed. The severity of brain injury, including periventricular leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain growth was assessed by using measures of biparietal width (BPW) and interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed across all cohorts (n = 297) by using the Bayley Scales of Infant Development, Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and evaluation for cerebral palsy. Of 325 infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury. Severe brain injury was more common in infants with lower Apgar scores, necrotizing enterocolitis, inotropic support, and patent ductus arteriosus. Severe brain injury was associated with delayed cognitive and motor development and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic support, patent ductus arteriosus, necrotizing enterocolitis, prolonged parenteral nutrition, and oxygen at 36 weeks and was associated with delayed cognitive development. In contrast, increased interhemispheric distance was related to male gender, dexamethasone use, and severe brain injury. It was also associated with reduced cognitive development, independent of BPW. At term-equivalent age, VPT infants showed both brain injury and impaired brain growth on MRI. Severe brain injury and impaired brain growth patterns were independently associated with perinatal risk factors and delayed cognitive development. Copyright © 2014 by the American Academy of Pediatrics.

  2. Hemispheric lateralization of topological organization in structural brain networks.

    Science.gov (United States)

    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.

  3. Decreased neural precursor cell pool in NADPH oxidase 2-deficiency: From mouse brain to neural differentiation of patient derived iPSC

    Directory of Open Access Journals (Sweden)

    Zeynab Nayernia

    2017-10-01

    Full Text Available There is emerging evidence for the involvement of reactive oxygen species (ROS in the regulation of stem cells and cellular differentiation. Absence of the ROS-generating NADPH oxidase NOX2 in chronic granulomatous disease (CGD patients, predominantly manifests as immune deficiency, but has also been associated with decreased cognition. Here, we investigate the role of NOX enzymes in neuronal homeostasis in adult mouse brain and in neural cells derived from human induced pluripotent stem cells (iPSC. High levels of NOX2 were found in mouse adult neurogenic regions. In NOX2-deficient mice, neurogenic regions showed diminished redox modifications, as well as decrease in neuroprecursor numbers and in expression of genes involved in neural differentiation including NES, BDNF and OTX2. iPSC from healthy subjects and patients with CGD were used to study the role of NOX2 in human in vitro neuronal development. Expression of NOX2 was low in undifferentiated iPSC, upregulated upon neural induction, and disappeared during neuronal differentiation. In human neurospheres, NOX2 protein and ROS generation were polarized within the inner cell layer of rosette structures. NOX2 deficiency in CGD-iPSCs resulted in an abnormal neural induction in vitro, as revealed by a reduced expression of neuroprogenitor markers (NES, BDNF, OTX2, NRSF/REST, and a decreased generation of mature neurons. Vector-mediated NOX2 expression in NOX2-deficient iPSCs rescued neurogenesis. Taken together, our study provides novel evidence for a regulatory role of NOX2 during early stages of neurogenesis in mouse and human.

  4. Lycium barbarum Extracts Protect the Brain from Blood-Brain Barrier Disruption and Cerebral Edema in Experimental Stroke

    Science.gov (United States)

    Yang, Di; Li, Suk-Yee; Yeung, Chung-Man; Chang, Raymond Chuen-Chung; So, Kwok-Fai; Wong, David; Lo, Amy C. Y.

    2012-01-01

    Background and Purpose Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model. Methods C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO. Results LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains. Conclusions Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke. PMID:22438957

  5. Decreased calcineurin immunoreactivity in the postmortem brain of a patient with schizophrenia who had been prescribed the calcineurin inhibitor, tacrolimus, for leukemia

    Directory of Open Access Journals (Sweden)

    Wada A

    2016-07-01

    Full Text Available Akira Wada,1,2 Yasuto Kunii,1 Jyunya Matsumoto,1 Mizuki Hino,1 Atsuko Nagaoka,1 Shin-ichi Niwa,3 Hirooki Yabe1 1Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, 2Department of Neuropsychiatry, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, 3Department of Psychiatry, Aizu Medical Center, Fukushima Medical University, Aizuwakamatsu City, Fukushima, Japan Background: The calcineurin (CaN inhibitor, tacrolimus, is widely used in patients undergoing allogeneic organ transplantation and in those with certain allergic diseases. Recently, several reports have suggested that CaN is also associated with schizophrenia. However, little data are currently available on the direct effect of tacrolimus on the human brain.Case: A 23-year-old Japanese female experienced severe delusion of persecution, delusional mood, suspiciousness, aggression, and excitement. She visited our hospital and was diagnosed with schizophrenia. When she was 27 years old, she had severe general fatigue, persistent fever, systemic joint pain, gingival bleeding, and breathlessness and was diagnosed with acute myelomonocytic leukemia. Later she underwent bone marrow transplantation (BMT, she was administered methotrexate and cyclosporin A to prevent graft versus host disease (GVHD. Three weeks after BMT, she showed initial symptoms of GVHD and was prescribed tacrolimus instead of cyclosporin A. Seven months after BMT at the age of 31 years, she died of progression of GVHD. Pathological anatomy was examined after her death, including immunohistochemical analysis of her brain using anti-CaN antibodies. For comparison, we used our previous data from both a schizophrenia group and a healthy control group. No significant differences were observed in the percentage of CaN-immunoreactive neurons among the schizophrenia group, healthy control group, and the tacrolimus case (all P>0.5, analysis of covariance. Compared with the

  6. Decreased Left Putamen and Thalamus Volume Correlates with Delusions in First-Episode Schizophrenia Patients

    Directory of Open Access Journals (Sweden)

    Xiaojun Huang

    2017-11-01

    Full Text Available BackgroundDelusional thinking is one of the hallmark symptoms of schizophrenia. However, the underlying neural substrate for delusions in schizophrenia remains unknown. In an attempt to further our understanding of the neural basis of delusions, we explored gray matter deficits and their clinical associations in first-episode schizophrenia patients with and without delusions.MethodsTwenty-four first-episode schizophrenia patients with delusions and 18 without delusions as well as 26 healthy controls (HC underwent clinical assessment and whole-brain structural imaging which were acquired a 3.0 T scanner. Voxel-based morphometry was used to explore inter-group differences in gray matter volume using analysis of covariance, and Spearman correlation coefficients (rho between the Scale for the Assessment of Positive Symptoms (SAPS-delusion scores and mean regional brain volumes was obtained.ResultsPatients with delusions showed decreased brain gray matter volumes in the left putamen, thalamus, and caudate regions compared with HC. Patients with delusions also showed decreased regional volume in the left putamen and thalamus compared with patients without delusions. SAPS-delusion scores were negatively correlated with the gray matter volumes of the left putamen and thalamus.DiscussionLeft putamen and thalamus volume loss may be biological correlates of delusions in schizophrenia.

  7. Neural Mobilization Treatment Decreases Glial Cells and Brain-Derived Neurotrophic Factor Expression in the Central Nervous System in Rats with Neuropathic Pain Induced by CCI in Rats

    Directory of Open Access Journals (Sweden)

    Aline Carolina Giardini

    2017-01-01

    Full Text Available Background. Glial cells are implicated in the development of chronic pain and brain-derived neurotropic factor (BDNF released from activated microglia contributes to the nociceptive transmission. Neural mobilization (NM technique is a method clinically effective in reducing pain sensitivity. Here we examined the involvement of glial cells and BDNF expression in the thalamus and midbrain after NM treatment in rats with chronic constriction injury (CCI. CCI was induced and rats were subsequently submitted to 10 sessions of NM, every other day, beginning 14 days after CCI. Thalamus and midbrain were analyzed for glial fibrillary acidic protein (GFAP, microglial cell OX-42, and BDNF using Immunohistochemistry and Western blot assays. Results. Thalamus and midbrain of CCI group showed increases in GFAP, OX-42, and BDNF expression compared with control group and, in contrast, showed decreases in GFAP, OX-42, and BDNF after NM when compared with CCI group. The decreased immunoreactivity for GFAP, OX-42, and BDNF in ventral posterolateral nucleus in thalamus and the periaqueductal gray in midbrain was shown by immunohistochemistry. Conclusions. These findings may improve the knowledge about the involvement of astrocytes, microglia, and BDNF in the chronic pain and show that NM treatment, which alleviates neuropathic pain, affects glial cells and BDNF expression.

  8. Direct observation during surgery shows preservation of cerebral microcirculation in patients with traumatic brain injury

    NARCIS (Netherlands)

    Pérez-Bárcena, Jon; Romay, Eduardo; Llompart-Pou, Juan Antonio; Ibáñez, Javier; Brell, Marta; Llinás, Pedro; González, Elsa; Merenda, Amedeo; Ince, Can; Bullock, Ross

    2015-01-01

    To describe the alterations of the cortical microcirculation of the brain (blood flow and vessel density) in TBI patients who and compare them with a control group. Prospective and observational study in a third-level university hospital. Cortical microcirculation in the brain was directly observed

  9. Alterations in regional homogeneity of resting-state brain activity in internet gaming addicts

    Directory of Open Access Journals (Sweden)

    Dong Guangheng

    2012-08-01

    Full Text Available Abstract Backgrounds Internet gaming addiction (IGA, as a subtype of internet addiction disorder, is rapidly becoming a prevalent mental health concern around the world. The neurobiological underpinnings of IGA should be studied to unravel the potential heterogeneity of IGA. This study investigated the brain functions in IGA patients with resting-state fMRI. Methods Fifteen IGA subjects and fourteen healthy controls participated in this study. Regional homogeneity (ReHo measures were used to detect the abnormal functional integrations. Results Comparing to the healthy controls, IGA subjects show enhanced ReHo in brainstem, inferior parietal lobule, left posterior cerebellum, and left middle frontal gyrus. All of these regions are thought related with sensory-motor coordination. In addition, IGA subjects show decreased ReHo in temporal, occipital and parietal brain regions. These regions are thought responsible for visual and auditory functions. Conclusions Our results suggest that long-time online game playing enhanced the brain synchronization in sensory-motor coordination related brain regions and decreased the excitability in visual and auditory related brain regions.

  10. Yi-gan san restores behavioral alterations and a decrease of brain glutathione level in a mouse model of schizophrenia.

    Science.gov (United States)

    Makinodan, Manabu; Yamauchi, Takahira; Tatsumi, Kouko; Okuda, Hiroaki; Noriyama, Yoshinobu; Sadamatsu, Miyuki; Kishimoto, Toshifumi; Wanaka, Akio

    2009-01-01

    The traditional Chinese herbal medicine yi-gan san has been used to cure neuropsychological disorders. Schizophrenia can be one of the target diseases of yi-gan san. We aimed at evaluating the possible use of yi-gan san in improving the schizophrenic symptoms of an animal model. Yi-gan san or distilled water was administered to mice born from pregnant mice injected with polyinosinic-polycytidilic acid or phosphate buffered saline. The former is a model of schizophrenia based on the epidemiological data that maternal infection leads to psychotic disorders including schizophrenia in the offspring. Prepulse inhibition and sensitivity to methamphetamine in open field tests were analyzed and the total glutathione content of whole brains was measured. Yi-gan san reversed the decrease in prepulse inhibition, hypersensitivity to methamphetamine and cognitive deficits found in the model mice to the level of control mice. Total glutathione content in whole brains was reduced in the model mice but was restored to normal levels by yi-gan san treatment. These results suggest that yi-gan san may have ameliorating effects on the pathological symptoms of schizophrenia.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

    OpenAIRE

    Volkow, Nora D.; Wang, Gene-Jack; Tomasi, Dardo; Telang, Frank; Fowler, Joanna S.; Pradhan, Kith; Jayne, Millard; Logan, Jean; Goldstein, Rita Z.; Alia-Klein, Nelly; Wong, Christopher

    2010-01-01

    Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and...

  13. Tianeptine, olanzapine and fluoxetine show similar restoring effects on stress induced molecular changes in mice brain: An FT-IR study

    Science.gov (United States)

    Türker-Kaya, Sevgi; Mutlu, Oğuz; Çelikyurt, İpek K.; Akar, Furuzan; Ulak, Güner

    2016-05-01

    Chronic stress which can cause a variety of disorders and illness ranging from metabolic and cardiovascular to mental leads to alterations in content, structure and dynamics of biomolecules in brain. The determination of stress-induced changes along with the effects of antidepressant treatment on these parameters might bring about more effective therapeutic strategies. In the present study, we investigated unpredictable chronic mild stress (UCMS)-induced changes in biomolecules in mouse brain and the restoring effects of tianeptine (TIA), olanzapine (OLZ) and fluoxetine (FLX) on these variations, by Fourier transform infrared (FT-IR) spectroscopy. The results revealed that chronic stress causes different membrane packing and an increase in lipid peroxidation, membrane fluidity. A significant increment for lipid/protein, Cdbnd O/lipid, CH3/lipid, CH2/lipid, PO-2/lipid, COO-/lipid and RNA/protein ratios but a significant decrease for lipid/protein ratios were also obtained. Additionally, altered protein secondary structure components were estimated, such as increment in random coils and beta structures. The administration of TIA, OLZ and FLX drugs restored these stress-induced variations except for alterations in protein structure and RNA/protein ratio. This may suggest that these drugs have similar restoring effects on the consequences of stress activity in brain, in spite of the differences in their action mechanisms. All findings might have importance in understanding molecular mechanisms underlying chronic stress and contribute to studies aimed for drug development.

  14. Studies of aluminum in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Lipman, J.J.; Brill, A.B.; Som, P.; Jones, K.W.; Colowick, S.; Cholewa, M.

    1985-01-01

    The effects of high aluminum concentrations in rat brains were studied using /sup 14/C autoradiography to measure the uptake of /sup 14/C 2-deoxy-D-glucose (/sup 14/C-2DG) and microbeam proton-induced x-ray emission (microPIXE) with a 20-..mu..m resolution to measure concentrations of magnesium, aluminum, potassium, and calcium. The aluminum was introduced intracisternally in the form of aluminum tartrate (Al-T) while control animals were given sodium tartrate (Na-T). The /sup 14/C was administered intravenously. The animals receiving Al-T developed seizure disorders and had pathological changes that included cerebral cortical atrophy. The results showed that there was a decreased uptake of /sup 14/C-2DG in cortical regions in which increased aluminum levels were measured, i.e., there is a correlation between the aluminum in the rat brain and decreased brain glucose metabolism. A minimum detection limit of about 16 ppM (mass fraction) or 3 x 10/sup 9/ Al atoms was obtained for Al under the conditions employed. 14 refs., 4 figs., 1 tab.

  15. Studies of aluminum in rat brain

    International Nuclear Information System (INIS)

    Lipman, J.J.; Brill, A.B.; Som, P.; Jones, K.W.; Colowick, S.; Cholewa, M.

    1985-01-01

    The effects of high aluminum concentrations in rat brains were studied using 14 C autoradiography to measure the uptake of 14 C 2-deoxy-D-glucose ( 14 C-2DG) and microbeam proton-induced x-ray emission (microPIXE) with a 20-μm resolution to measure concentrations of magnesium, aluminum, potassium, and calcium. The aluminum was introduced intracisternally in the form of aluminum tartrate (Al-T) while control animals were given sodium tartrate (Na-T). The 14 C was administered intravenously. The animals receiving Al-T developed seizure disorders and had pathological changes that included cerebral cortical atrophy. The results showed that there was a decreased uptake of 14 C-2DG in cortical regions in which increased aluminum levels were measured, i.e., there is a correlation between the aluminum in the rat brain and decreased brain glucose metabolism. A minimum detection limit of about 16 ppM (mass fraction) or 3 x 10 9 Al atoms was obtained for Al under the conditions employed. 14 refs., 4 figs., 1 tab

  16. Administration of caffeine inhibited adenosine receptor agonist-induced decreases in motor performance, thermoregulation, and brain neurotransmitter release in exercising rats.

    Science.gov (United States)

    Zheng, Xinyan; Hasegawa, Hiroshi

    2016-01-01

    We examined the effects of an adenosine receptor agonist on caffeine-induced changes in thermoregulation, neurotransmitter release in the preoptic area and anterior hypothalamus, and endurance exercise performance in rats. One hour before the start of exercise, rats were intraperitoneally injected with either saline alone (SAL), 10 mg kg(-1) caffeine and saline (CAF), a non-selective adenosine receptor agonist (5'-N-ethylcarboxamidoadenosine [NECA]: 0.5 mg kg(-1)) and saline (NECA), or the combination of caffeine and NECA (CAF+NECA). Rats ran until fatigue on the treadmill with a 5% grade at a speed of 18 m min(-1) at 23 °C. Compared to the SAL group, the run time to fatigue (RTTF) was significantly increased by 52% following caffeine administration and significantly decreased by 65% following NECA injection (SAL: 91 ± 14.1 min; CAF: 137 ± 25.8 min; NECA: 31 ± 13.7 min; CAF+NECA: 85 ± 11.8 min; pcaffeine injection inhibited the NECA-induced decreases in the RTTF, Tcore, heat production, heat loss, and extracellular DA release. Neither caffeine nor NECA affected extracellular noradrenaline or serotonin release. These results support the findings of previous studies showing improved endurance performance and overrides in body limitations after caffeine administration, and imply that the ergogenic effects of caffeine may be associated with the adenosine receptor blockade-induced increases in brain DA release. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. 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

    not linearly correlated (r 2 =0.045, p>0.05). Global CBF was decreased, unchanged, or increased immediately after the WBI in the patients with brain metastasis. The patients with immediate WBI effect showed increase in global mean CBF, but without significant lengthening in survival compared with the patients without CBF increase. (author)

  18. Ob/ob mouse livers show decreased oxidative phosphorylation efficiencies and anaerobic capacities after cold ischemia.

    Directory of Open Access Journals (Sweden)

    Michael J J Chu

    Full Text Available BACKGROUND: Hepatic steatosis is a major risk factor for graft failure in liver transplantation. Hepatic steatosis shows a greater negative influence on graft function following prolonged cold ischaemia. As the impact of steatosis on hepatocyte metabolism during extended cold ischaemia is not well-described, we compared markers of metabolic capacity and mitochondrial function in steatotic and lean livers following clinically relevant durations of cold preservation. METHODS: Livers from 10-week old leptin-deficient obese (ob/ob, n = 9 and lean C57 mice (n = 9 were preserved in ice-cold University of Wisconsin solution. Liver mitochondrial function was then assessed using high resolution respirometry after 1.5, 3, 5, 8, 12, 16 and 24 hours of storage. Metabolic marker enzymes for anaerobiosis and mitochondrial mass were also measured in conjunction with non-bicarbonate tissue pH buffering capacity. RESULTS: Ob/ob and lean mice livers showed severe (>60% macrovesicular and mild (<30% microvesicular steatosis on Oil Red O staining, respectively. Ob/ob livers had lower baseline enzymatic complex I activity but similar adenosine triphosphate (ATP levels compared to lean livers. During cold storage, the respiratory control ratio and complex I-fueled phosphorylation deteriorated approximately twice as fast in ob/ob livers compared to lean livers. Ob/ob livers also demonstrated decreased ATP production capacities at all time-points analyzed compared to lean livers. Ob/ob liver baseline lactate dehydrogenase activities and intrinsic non-bicarbonate buffering capacities were depressed by 60% and 40%, respectively compared to lean livers. CONCLUSIONS: Steatotic livers have impaired baseline aerobic and anaerobic capacities compared to lean livers, and mitochondrial function indices decrease particularly from after 5 hours of cold preservation. These data provide a mechanistic basis for the clinical recommendation of shorter cold storage durations in

  19. Aquaporin-11 (AQP11 Expression in the Mouse Brain

    Directory of Open Access Journals (Sweden)

    Shin Koike

    2016-06-01

    Full Text Available Aquaporin-11 (AQP11 is an intracellular aquaporin expressed in various tissues, including brain tissues in mammals. While AQP11-deficient mice have developed fatal polycystic kidneys at one month old, the role of AQP11 in the brain was not well appreciated. In this study, we examined the AQP11 expression in the mouse brain and the brain phenotype of AQP11-deficient mice. AQP11 messenger ribonucleic acid (mRNA and protein were expressed in the brain, but much less than in the thymus and kidney. Immunostaining showed that AQP11 was localized at the epithelium of the choroid plexus and at the endothelium of the brain capillary, suggesting that AQP11 may be involved in water transport at the choroid plexus and blood-brain barrier (BBB in the brain. The expression of AQP4, another brain AQP expressed at the BBB, was decreased by half in AQP11-deficient mice, thereby suggesting the presence of the interaction between AQP11 and AQP4. The brain of AQP11-deficient mice, however, did not show any morphological abnormalities and the function of the BBB was intact. Our findings provide a novel insight into a water transport mechanism mediated by AQPs in the brain, which may lead to a new therapy for brain edema.

  20. Effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    WANG Qiong; LI Ai-lin; ZHI Da-shi; HUANG Hui-ling

    2007-01-01

    Objective:To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (STBI) using clinical microdialysis.Methods: Thirty-one patients with STBI ( GCS ≤8) were randomly divided into hypothermic group (Group A) and control group (Group B). Microdialysis catheters were inserted into the cerebral cortex of perilesional and normal brain tissue. All samples were analyzed using CMA microdialysis analyzer.Results: In comparison with the control group, lactate/glucose ratio ( L/G) , lactate/pyruvate ratio ( L/P) and glycerol (Gly) in perilensional tissue were significantly decreased; L/P in normal brain tissue was significantly decreased. In control group, L/G, L/P and Gly in perilensional tissue were higher than that in normal brain tissue. In the hypothermic group, L/P in perilensional tissue was higher than that in relative normal brain.Conclusions: Mild hypothermia protects brain tissues by decreasing L/G, L/P and Gly in perilensional tissue and L/P in "normal brain" tissues. The energy crisis and membrane phospholipid degradation in perilensional tissue are easier to happen after traumatic brain injury, and mild hypothermia protects brain better in perilensional tissue than in normal brain tissue.

  1. Incidence of Brain Atrophy and Decline in Mini-Mental State Examination Score After Whole-Brain Radiotherapy in Patients With Brain Metastases: A Prospective Study

    International Nuclear Information System (INIS)

    Shibamoto, Yuta; Baba, Fumiya; Oda, Kyota; Hayashi, Shinya; Kokubo, Masaki; Ishihara, Shun-Ichi; Itoh, Yoshiyuki; Ogino, Hiroyuki; Koizumi, Masahiko

    2008-01-01

    Purpose: To determine the incidence of brain atrophy and dementia after whole-brain radiotherapy (WBRT) in patients with brain metastases not undergoing surgery. Methods and Materials: Eligible patients underwent WBRT to 40 Gy in 20 fractions with or without a 10-Gy boost. Brain magnetic resonance imaging or computed tomography and Mini-Mental State Examination (MMSE) were performed before and soon after radiotherapy, every 3 months for 18 months, and every 6 months thereafter. Brain atrophy was evaluated by change in cerebrospinal fluid-cranial ratio (CCR), and the atrophy index was defined as postradiation CCR divided by preradiation CCR. Results: Of 101 patients (median age, 62 years) entering the study, 92 completed WBRT, and 45, 25, and 10 patients were assessable at 6, 12, and 18 months, respectively. Mean atrophy index was 1.24 ± 0.39 (SD) at 6 months and 1.32 ± 0.40 at 12 months, and 18% and 28% of the patients had an increase in the atrophy index by 30% or greater, respectively. No apparent decrease in mean MMSE score was observed after WBRT. Individually, MMSE scores decreased by four or more points in 11% at 6 months, 12% at 12 months, and 0% at 18 months. However, about half the decrease in MMSE scores was associated with a decrease in performance status caused by systemic disease progression. Conclusions: Brain atrophy developed in up to 30% of patients, but it was not necessarily accompanied by MMSE score decrease. Dementia after WBRT unaccompanied by tumor recurrence was infrequent

  2. Antenatal antioxidant treatment with melatonin to decrease newborn neurodevelopmental deficits and brain injury caused by fetal growth restriction.

    Science.gov (United States)

    Miller, Suzanne L; Yawno, Tamara; Alers, Nicole O; Castillo-Melendez, Margie; Supramaniam, Veena G; VanZyl, Niel; Sabaretnam, Tharani; Loose, Jan M; Drummond, Grant R; Walker, David W; Jenkin, Graham; Wallace, Euan M

    2014-04-01

    Fetal intrauterine growth restriction (IUGR) is a serious pregnancy complication associated with increased rates of perinatal morbidity and mortality, and ultimately with long-term neurodevelopmental impairments. No intervention currently exists that can improve the structure and function of the IUGR brain before birth. Here, we investigated whether maternal antenatal melatonin administration reduced brain injury in ovine IUGR. IUGR was induced in pregnant sheep at 0.7 gestation and a subset of ewes received melatonin via intravenous infusion until term. IUGR, IUGR + melatonin (IUGR + MLT) and control lambs were born naturally, neonatal behavioral assessment was used to examine neurological function and at 24 hr after birth the brain was collected for the examination of neuropathology. Compared to control lambs, IUGR lambs took significantly longer to achieve normal neonatal lamb behaviors, such as standing and suckling. IUGR brains showed widespread cellular and axonal lipid peroxidation, and white matter hypomyelination and axonal damage. Maternal melatonin administration ameliorated oxidative stress, normalized myelination and rescued axonopathy within IUGR lamb brains, and IUGR + MLT lambs demonstrated significant functional improvements including a reduced time taken to attach to and suckle at the udder after birth. Based on these observations, we began a pilot clinical trial of oral melatonin administration to women with an IUGR fetus. Maternal melatonin was not associated with adverse maternal or fetal effects and it significantly reduced oxidative stress, as evidenced by reduced malondialdehyde levels, in the IUGR + MLT placenta compared to IUGR alone. Melatonin should be considered for antenatal neuroprotective therapy in human IUGR. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. A preliminary DTI study showing no brain structural change associated with adolescent cannabis use

    Directory of Open Access Journals (Sweden)

    Brown Kyle

    2006-05-01

    Full Text Available Abstract Analyses were performed on brain MRI scans from individuals who were frequent cannabis users (N = 10; 9 males, 1 female, mean age 21.1 ± 2.9, range: 18–27 in adolescence and similar age and sex matched young adults who never used cannabis (N = 10; 9 males, 1 female, mean age of 23.0 ± 4.4, range: 17–30. Cerebral atrophy and white matter integrity were determined using diffusion tensor imaging (DTI to quantify the apparent diffusion coefficient (ADC and the fractional anisotropy (FA. Whole brain volumes, lateral ventricular volumes, and gray matter volumes of the amygdala-hippocampal complex, superior temporal gyrus, and entire temporal lobes (excluding the amygdala-hippocampal complex were also measured. While differences existed between groups, no pattern consistent with evidence of cerebral atrophy or loss of white matter integrity was detected. It is concluded that frequent cannabis use is unlikely to be neurotoxic to the normal developing adolescent brain.

  4. 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

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

    Science.gov (United States)

    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.

  6. 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)

    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.

  7. Miliary Tuberculosis with Concurrent Brain and Spinal Cord Involvement: A Case Report

    International Nuclear Information System (INIS)

    Sung, Chang Keun; Na, Hyoung Il; Yu, Hyeon; Byun, Jun Soo; Youn, Young Chul; Seo, Jae Seung; Kim, Gi Hyeon

    2008-01-01

    Central nervous system involvement by tuberculosis is rare, and intramedullary involvement is even more rare. A patient that developed intermittent amnesia during anti-tuberculous therapy underwent brain CT and MRI and spine MRI. The latter showed multiple small enhancing nodules in the brain and spinal cord. The patient was treated with anti-tuberculous medication and steroids under the suspected diagnosis of miliary tuberculosis. Follow-up CT showed decreased nodule size and number. We report a case of miliary tuberculosis in the brain and spinal cord and present a review of the literature related to similar cases

  8. Miliary Tuberculosis with Concurrent Brain and Spinal Cord Involvement: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Chang Keun; Na, Hyoung Il; Yu, Hyeon; Byun, Jun Soo; Youn, Young Chul; Seo, Jae Seung; Kim, Gi Hyeon [Chung-Ang University, Seoul (Korea, Republic of)

    2008-11-15

    Central nervous system involvement by tuberculosis is rare, and intramedullary involvement is even more rare. A patient that developed intermittent amnesia during anti-tuberculous therapy underwent brain CT and MRI and spine MRI. The latter showed multiple small enhancing nodules in the brain and spinal cord. The patient was treated with anti-tuberculous medication and steroids under the suspected diagnosis of miliary tuberculosis. Follow-up CT showed decreased nodule size and number. We report a case of miliary tuberculosis in the brain and spinal cord and present a review of the literature related to similar cases.

  9. Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme

    Science.gov (United States)

    Yui, Daishi; Nishida, Yoichiro; Nishina, Tomoko; Mogushi, Kaoru; Tajiri, Mio; Ishibashi, Satoru; Ajioka, Itsuki; Ishikawa, Kinya; Mizusawa, Hidehiro; Murayama, Shigeo; Yokota, Takanori

    2015-01-01

    Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD) model mice showed decreased insulin-degrading enzyme (IDE) levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa -/-) mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa -/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3); Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa -/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD. PMID:26637123

  10. Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme.

    Directory of Open Access Journals (Sweden)

    Daishi Yui

    Full Text Available Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD model mice showed decreased insulin-degrading enzyme (IDE levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa-/- mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa-/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3; Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa-/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD.

  11. Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex.

    Science.gov (United States)

    Kutsuna, Nobuo; Yamashita, Akiko; Eriguchi, Takashi; Oshima, Hideki; Suma, Takeshi; Sakatani, Kaoru; Yamamoto, Takamitsu; Yoshino, Atsuo; Katayama, Yoichi

    2014-01-01

    Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  12. FEMALE MICE ARE RESISTANT TO Fabp1 GENE ABLATION-INDUCED ALTERATIONS IN BRAIN ENDOCANNABINOID LEVELS

    Science.gov (United States)

    Martin, Gregory G.; Chung, Sarah; Landrock, Danilo; Landrock, Kerstin K.; Dangott, Lawrence J.; Peng, Xiaoxue; Kaczocha, Martin; Murphy, Eric J.; Kier, Ann B.; Schroeder, Friedhelm

    2017-01-01

    Although liver fatty acid binding protein (FABP1, L-FABP) is not detectable in brain, Fabp1 gene ablation (LKO) markedly increases endocannabinoids (EC) in brains of male mice. Since the brain EC system of females differs significantly from that of males, it was important to determine if LKO differently impacted the brain EC system. LKO did not alter brain levels of arachidonic acid (ARA)-containing ECs, i.e arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), but decreased non-ARA-containing N-acylethanolamides (OEA, PEA) and 2-oleoylglycerol (2-OG) that potentiate the actions of AEA and 2-AG. These changes in brain potentiating EC levels were not associated with: i) a net decrease in levels of brain membrane proteins associated with fatty acid uptake and EC synthesis; ii) a net increase in brain protein levels of cytosolic EC chaperones and enzymes in EC degradation; or iii) increased brain protein levels of EC receptors (CB1, TRVP1). Instead, the reduced or opposite responsiveness of female brain EC levels to loss of FABP1 (LKO) correlated with intrinsically lower FABP1 level in livers of WT females than males. These data show that female mouse brain endocannabinoid levels were unchanged (AEA, 2-AG) or decreased (OEA, PEA, 2-OG) by complete loss of FABP1 (LKO). PMID:27450559

  13. Longitudinal Changes in Total Brain Volume in Schizophrenia: Relation to Symptom Severity, Cognition and Antipsychotic Medication

    NARCIS (Netherlands)

    Veijola, J.; Guo, J.Y.; Moilanen, J.S.; Jaaskelainen, E.; Miettunen, J.; Kyllonen, M.; Haapea, M.; Huhtaniska, S.; Alaraisanen, A.; Maki, P.; Kiviniemi, V.; Nikkinen, J.; Starck, T.; Remes, J.J.; Tanskanen, P.; Tervonen, O.; Wink, A.M.; Kehagia, A.; Suckling, J.; Kobayashi, H.; Barnett, J.H.; Barnes, A.; Koponen, H.J.; Jones, P.B.; Isohanni, M.; Murray, G.K.

    2014-01-01

    Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population

  14. 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

  15. 99mTc-HMPAO Brain SPECT in Seizure Disorder: Comparison Brain SPECT, MRI / CT and EEG

    International Nuclear Information System (INIS)

    Yang, Hyung In; Im, Ju Hyuk; Choi, Chang Woon; Lee, Dong Soo; Chung, June Key; No, Jae Kyu; Lee, Myung Chul; Koh, Chang Soon

    1994-01-01

    We studied 115 patients with seizure who had been performed brain SPECT brain MRI of CT and EEG. To evaluate the pattern of brain SPECT in seizure patients 28 of them had secondary epilepsies, 87 had primary epilepsies. In primary epilepsies, 42 were generalized seizure and 45 were partial seizure. The causes of secondary epilepsies were congenital malformation, cerebromalacia, cerebral infarction ultiple sclerosis, AV-malformation. granuloma and etc, in order. In 28 secondary epilepsies, 25 of them, brain SPECT lesions was concordant with MRI or CT lesions. 3 were disconcordant. The brain SPECT findings of generalized seizure were normal in 22 patients, diffuse irregular decreased perfusion in 8, decreased in frontal cortex in 4. temporal in 5 and frontotemporal in 3. In 45 partial seizure, 19 brain SPECT were concordant with EEG (42.4%).

  16. Mental training affects distribution of limited brain resources.

    Directory of Open Access Journals (Sweden)

    Heleen A Slagter

    2007-06-01

    Full Text Available The information processing capacity of the human mind is limited, as is evidenced by the so-called "attentional-blink" deficit: When two targets (T1 and T2 embedded in a rapid stream of events are presented in close temporal proximity, the second target is often not seen. This deficit is believed to result from competition between the two targets for limited attentional resources. Here we show, using performance in an attentional-blink task and scalp-recorded brain potentials, that meditation, or mental training, affects the distribution of limited brain resources. Three months of intensive mental training resulted in a smaller attentional blink and reduced brain-resource allocation to the first target, as reflected by a smaller T1-elicited P3b, a brain-potential index of resource allocation. Furthermore, those individuals that showed the largest decrease in brain-resource allocation to T1 generally showed the greatest reduction in attentional-blink size. These observations provide novel support for the view that the ability to accurately identify T2 depends upon the efficient deployment of resources to T1. The results also demonstrate that mental training can result in increased control over the distribution of limited brain resources. Our study supports the idea that plasticity in brain and mental function exists throughout life and illustrates the usefulness of systematic mental training in the study of the human mind.

  17. Decreased Cerebellar-Orbitofrontal Connectivity Correlates with Stuttering Severity: Whole-Brain Functional and Structural Connectivity Associations with Persistent Developmental Stuttering.

    Science.gov (United States)

    Sitek, Kevin R; Cai, Shanqing; Beal, Deryk S; Perkell, Joseph S; Guenther, Frank H; Ghosh, Satrajit S

    2016-01-01

    Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex (OFC). Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and OFC may underlie successful compensatory mechanisms by more fluent stutterers.

  18. Decreased Cerebellar-Orbitofrontal Connectivity Correlates with Stuttering Severity: Whole-Brain Functional and Structural Connectivity Associations with Persistent Developmental Stuttering

    Science.gov (United States)

    Sitek, Kevin R.; Cai, Shanqing; Beal, Deryk S.; Perkell, Joseph S.; Guenther, Frank H.; Ghosh, Satrajit S.

    2016-01-01

    Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex (OFC). Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and OFC may underlie successful compensatory mechanisms by more fluent stutterers. PMID:27199712

  19. Yi-Gan San Restores Behavioral Alterations and a Decrease of Brain Glutathione Level in a Mouse Model of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Manabu Makinodan M.D.

    2009-01-01

    Full Text Available The traditional Chinese herbal medicine yi-gan san has been used to cure neuropsychological disorders. Schizophrenia can be one of the target diseases of yi-gan san. We aimed at evaluating the possible use of yi-gan san in improving the schizophrenic symptoms of an animal model. Yi-gan san or distilled water was administered to mice born from pregnant mice injected with polyinosinic-polycytidilic acid or phosphate buffered saline. The former is a model of schizophrenia based on the epidemiological data that maternal infection leads to psychotic disorders including schizophrenia in the offspring. Prepulse inhibition and sensitivity to methamphetamine in open field tests were analyzed and the total glutathione content of whole brains was measured. Yi-gan san reversed the decrease in prepulse inhibition, hypersensitivity to methamphetamine and cognitive deficits found in the model mice to the level of control mice. Total glutathione content in whole brains was reduced in the model mice but was restored to normal levels by yi-gan san treatment. These results suggest that yi-gan san may have ameliorating effects on the pathological symptoms of schizophrenia.

  20. Decreased cerebellar-orbitofrontal connectivity correlates with stuttering severity: Whole-brain functional and structural connectivity associations with persistent developmental stuttering

    Directory of Open Access Journals (Sweden)

    Kevin Richard Sitek

    2016-05-01

    Full Text Available Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here, we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex. Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and orbitofrontal cortex may underlie successful compensatory mechanisms by more fluent stutterers.

  1. Analysis of Biotinylated Generation 4 Poly(amidoamine (PAMAM Dendrimer Distribution in the Rat Brain and Toxicity in a Cellular Model of the Blood-Brain Barrier

    Directory of Open Access Journals (Sweden)

    Heather A. Bullen

    2013-09-01

    Full Text Available Dendrimers are highly customizable nanopolymers with qualities that make them ideal for drug delivery. The high binding affinity of biotin/avidin provides a useful approach to fluorescently label synthesized dendrimer-conjugates in cells and tissues. In addition, biotin may facilitate delivery of dendrimers through the blood-brain barrier (BBB via carrier-mediated endocytosis. The purpose of this research was to: (1 measure toxicity using lactate dehydrogenase (LDH assays of generation (G4 biotinylated and non-biotinylated poly(amidoamine (PAMAM dendrimers in a co-culture model of the BBB, (2 determine distribution of dendrimers in the rat brain, kidney, and liver following systemic administration of dendrimers, and (3 conduct atomic force microscopy (AFM on rat brain sections following systemic administration of dendrimers. LDH measurements showed that biotinylated dendrimers were toxic to cell co-culture after 48 h of treatment. Distribution studies showed evidence of biotinylated and non-biotinylated PAMAM dendrimers in brain. AFM studies showed evidence of dendrimers only in brain tissue of treated rats. These results indicate that biotinylation does not decrease toxicity associated with PAMAM dendrimers and that biotinylated PAMAM dendrimers distribute in the brain. Furthermore, this article provides evidence of nanoparticles in brain tissue following systemic administration of nanoparticles supported by both fluorescence microscopy and AFM.

  2. Regional Brain Activation during Meditation Shows Time and Practice Effects: An Exploratory FMRI Study

    Directory of Open Access Journals (Sweden)

    E. Baron Short

    2010-01-01

    Full Text Available Meditation involves attentional regulation and may lead to increased activity in brain regions associated with attention such as dorsal lateral prefrontal cortex (DLPFC and anterior cingulate cortex (ACC. Using functional magnetic resonance imaging, we examined whether DLPFC and ACC were activated during meditation. Subjects who meditate were recruited and scanned on a 3.0 Tesla scanner. Subjects meditated for four sessions of 12 min and performed four sessions of a 6 min control task. Individual and group t-maps were generated of overall meditation response versus control response and late meditation response versus early meditation response for each subject and time courses were plotted. For the overall group (n = 13, and using an overall brain analysis, there were no statistically significant regional activations of interest using conservative thresholds. A region of interest analysis of the entire group time courses of DLPFC and ACC were statistically more active throughout meditation in comparison to the control task. Moreover, dividing the cohort into short (n = 8 and long-term (n = 5 practitioners (>10 years revealed that the time courses of long-term practitioners had significantly more consistent and sustained activation in the DLPFC and the ACC during meditation versus control in comparison to short-term practitioners. The regional brain activations in the more practised subjects may correlate with better sustained attention and attentional error monitoring. In summary, brain regions associated with attention vary over the time of a meditation session and may differ between long- and short-term meditation practitioners.

  3. Cognitive benefit and cost of acute stress is differentially modulated by individual brain state.

    Science.gov (United States)

    Kohn, Nils; Hermans, Erno J; Fernández, Guillén

    2017-07-01

    Acute stress is associated with beneficial as well as detrimental effects on cognition in different individuals. However, it is not yet known how stress can have such opposing effects. Stroop-like tasks typically show this dissociation: stress diminishes speed, but improves accuracy. We investigated accuracy and speed during a stroop-like task of 120 healthy male subjects after an experimental stress induction or control condition in a randomized, counter-balanced cross-over design; we assessed brain-behavior associations and determined the influence of individual brain connectivity patterns on these associations, which may moderate the effect and help identify stress resilience factors. In the mean, stress was associated to increase in accuracy, but decrease in speed. Accuracy was associated to brain activation in a distributed set of brain regions overlapping with the executive control network (ECN) and speed to temporo-parietal activation. In line with a stress-related large-scale network reconfiguration, individuals showing an upregulation of the salience and down-regulation of the executive-control network under stress displayed increased speed, but decreased performance. In contrast, individuals who upregulate their ECN under stress show improved performance. Our results indicate that the individual large-scale brain network balance under acute stress moderates cognitive consequences of threat. © The Author (2017). Published by Oxford University Press.

  4. Subcortical heterotopia appearing as huge midline mass in the newborn brain.

    Science.gov (United States)

    Fukumura, Shinobu; Watanabe, Toshihide; Kimura, Sachiko; Ochi, Satoko; Yoshifuji, Kazuhisa; Tsutsumi, Hiroyuki

    2016-02-01

    We report the case of a 2-year-old boy who showed a huge midline mass in the brain at prenatal assessment. After birth, magnetic resonance imaging (MRI) revealed a conglomerate mass with an infolded microgyrus at the midline, which was suspected as a midline brain-in-brain malformation. MRI also showed incomplete cleavage of his frontal cortex and thalamus, consistent with lobar holoprosencephaly. The patient underwent an incisional biopsy of the mass on the second day of life. The mass consisted of normal central nervous tissue with gray and white matter, representing a heterotopic brain. The malformation was considered to be a subcortical heterotopia. With maturity, focal signal changes and decreased cerebral perfusion became clear on brain imaging, suggesting secondary glial degeneration. Coincident with these MRI abnormalities, the child developed psychomotor retardation and severe epilepsy focused on the side of the intracranial mass.

  5. Clinical applications of brain perfusion imaging with 99mTc-HM-PAO

    International Nuclear Information System (INIS)

    Lin Xiangtong

    1989-01-01

    200 patients with central nervous system diseases were studied with 99m Tc-HM-PAO and SPECT, including Parkinson's disease (PD) 47, Vascular headache 69, CVD 34, Epilepsy 26, Head truma 10, Brain tumor 5 and other 9 cases. Part of them have been compared with the results of MRI, X-CT and EEG. The positivity of SPECT in PD is 61.7% with decrease perfusion in local area of cerebram and basal ganglia and only 4 cases had lower perfusion in cerebellum; in headache is 46.4%, showing variable perfusion patterns; in CVD is 79.4% with decrease perfusion, luxury perfusion and the phenomenon of 'diaschsis'. In epilepsy, the abnormal foci mostly localize in temporal lobe and have close relation to the results of EEG. In brain tumor it also denotes decreased uptake of tracer. The clinicl singnificance of brain perfusion imaging with 99m Tc-HM-PAO was discussed

  6. Fresh Frozen Plasma Modulates Brain Gene Expression in a Swine Model of Traumatic Brain Injury and Shock

    DEFF Research Database (Denmark)

    Sillesen, Martin; Bambakidis, Ted; Dekker, Simone E

    2017-01-01

    BACKGROUND: Resuscitation with fresh frozen plasma (FFP) decreases brain lesion size and swelling in a swine model of traumatic brain injury and hemorrhagic shock. We hypothesized that brain gene expression profiles after traumatic brain injury and hemorrhagic shock would be modulated by FFP resu...

  7. Modeling Early Postnatal Brain Growth and Development with CT: Changes in the Brain Radiodensity Histogram from Birth to 2 Years.

    Science.gov (United States)

    Cauley, K A; Hu, Y; Och, J; Yorks, P J; Fielden, S W

    2018-04-01

    The majority of brain growth and development occur in the first 2 years of life. This study investigated these changes by analysis of the brain radiodensity histogram of head CT scans from the clinical population, 0-2 years of age. One hundred twenty consecutive head CTs with normal findings meeting the inclusion criteria from children from birth to 2 years were retrospectively identified from 3 different CT scan platforms. Histogram analysis was performed on brain-extracted images, and histogram mean, mode, full width at half maximum, skewness, kurtosis, and SD were correlated with subject age. The effects of scan platform were investigated. Normative curves were fitted by polynomial regression analysis. Average total brain volume was 360 cm 3 at birth, 948 cm 3 at 1 year, and 1072 cm 3 at 2 years. Total brain tissue density showed an 11% increase in mean density at 1 year and 19% at 2 years. Brain radiodensity histogram skewness was positive at birth, declining logarithmically in the first 200 days of life. The histogram kurtosis also decreased in the first 200 days to approach a normal distribution. Direct segmentation of CT images showed that changes in brain radiodensity histogram skewness correlated with, and can be explained by, a relative increase in gray matter volume and an increase in gray and white matter tissue density that occurs during this period of brain maturation. Normative metrics of the brain radiodensity histogram derived from routine clinical head CT images can be used to develop a model of normal brain development. © 2018 by American Journal of Neuroradiology.

  8. Task-related signal decrease on functional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Hara, Yoshie; Nakamura, Mitsugu; Tamaki, Norihiko; Tamura, Shogo; Kitamura, Junji

    2001-01-01

    An atypical pattern of signal change was identified on functional magnetic resonance (fMR) imaging in pathologic patients. Three normal volunteers and 34 patients with pathologic lesions near the primary motor cortex underwent fMR imaging with echo-planar imaging while performing a hand motor task. Signal intensities were evaluated with the z-score method, and the time course and changes of the signal intensity were calculated. Nine of the 34 patients with pathologic lesions displayed a significant task-related signal reduction in motor-related areas. They also presented a conventional task-related signal increase in other motor-related areas. The time courses of the increase and decrease were the inverse of each other. There was no significant difference between rates of signal increase and decrease. Our findings suggest that this atypical signal decrease is clinically significant, and that impaired vascular reactivity and altered oxygen metabolism could contribute to the task-related signal reduction. Brain areas showing such task-related signal decrease should be preserved at surgery. (author)

  9. Brains with sporadic Creutzfeldt-Jakob disease and copathology showed a prolonged end-stage of disease.

    Science.gov (United States)

    Miguelez-Rodriguez, Aitzol; Santos-Juanes, Jorge; Vicente-Etxenausia, Ikerne; Perez de Heredia-Goñi, Katty; Garcia, Beatriz; Quiros, Luis M; Lorente-Gea, Laura; Guerra-Merino, Isabel; Aguirre, Jose J; Fernandez-Vega, Ivan

    2018-05-01

    To investigate the expression of major proteins related to primary neurodegenerative diseases and their prognostic significance in brains with Creutzfeldt-Jakob disease (CJD). Thirty consecutive cases of confirmed CJD during the period 2010-2015 at Basque Brain bank were retrospectively reviewed. Moreover, major neurodegenerative-associated proteins (phosphorylated Tau, 4R tau, 3R tau, alpha-synuclein, TDP43, amyloid beta) were tested. Clinical data were reviewed. Cases were divided according to the presence or absence of copathology. Survival curves were also determined. Copathology was significantly associated with survival in brains with CJD (4.2±1.2 vs 9.2±1.9; P=0.019) and in brains with MM1/MV1 CJD (2.1±1.0 vs 6.7±2.8; P=0.012). Besides, the presence of more than one major neurodegenerative-associated protein was significantly associated with survival (4.2±1.2 vs 10.7±2.6; P=0.017). Thus, univariate analyses further pointed out variables significantly associated with better survival: copathology in CJD (HR=0.430; P=0.033); more than one neurodegenerative-associated protein in CJD (HR=0.369; P=0.036) and copathology in MM1/MV1 CJD (HR=0.525; P=0.032). The existence of copathology significantly prolongs survival in patients with rapidly progressive dementia due to CJD. The study of major neurodegenerative-associated proteins in brains with CJD could allow us to further understand the molecular mechanisms behind prion diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

    Science.gov (United States)

    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

  11. Murine cytomegalovirus infection of neural stem cells alters neurogenesis in the developing brain.

    Directory of Open Access Journals (Sweden)

    Manohar B Mutnal

    2011-01-01

    Full Text Available Congenital cytomegalovirus (CMV brain infection causes serious neuro-developmental sequelae including: mental retardation, cerebral palsy, and sensorineural hearing loss. But, the mechanisms of injury and pathogenesis to the fetal brain are not completely understood. The present study addresses potential pathogenic mechanisms by which this virus injures the CNS using a neonatal mouse model that mirrors congenital brain infection. This investigation focused on, analysis of cell types infected with mouse cytomegalovirus (MCMV and the pattern of injury to the developing brain.We used our MCMV infection model and a multi-color flow cytometry approach to quantify the effect of viral infection on the developing brain, identifying specific target cells and the consequent effect on neurogenesis. In this study, we show that neural stem cells (NSCs and neuronal precursor cells are the principal target cells for MCMV in the developing brain. In addition, viral infection was demonstrated to cause a loss of NSCs expressing CD133 and nestin. We also showed that infection of neonates leads to subsequent abnormal brain development as indicated by loss of CD24(hi cells that incorporated BrdU. This neonatal brain infection was also associated with altered expression of Oct4, a multipotency marker; as well as down regulation of the neurotrophins BDNF and NT3, which are essential to regulate the birth and differentiation of neurons during normal brain development. Finally, we report decreased expression of doublecortin, a marker to identify young neurons, following viral brain infection.MCMV brain infection of newborn mice causes significant loss of NSCs, decreased proliferation of neuronal precursor cells, and marked loss of young neurons.

  12. {sup 99m}Tc-HMPAO Brain SPECT in Seizure Disorder: Comparison Brain SPECT, MRI / CT and EEG

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hyung In [Kyunghee University Hospital, Seoul (Korea, Republic of); Im, Ju Hyuk; Choi, Chang Woon; Lee, Dong Soo; Chung, June Key; No, Jae Kyu; Lee, Myung Chul; Koh, Chang Soon [Seoul National University Hospital, Seoul (Korea, Republic of)

    1994-03-15

    We studied 115 patients with seizure who had been performed brain SPECT brain MRI of CT and EEG. To evaluate the pattern of brain SPECT in seizure patients 28 of them had secondary epilepsies, 87 had primary epilepsies. In primary epilepsies, 42 were generalized seizure and 45 were partial seizure. The causes of secondary epilepsies were congenital malformation, cerebromalacia, cerebral infarction ultiple sclerosis, AV-malformation. granuloma and etc, in order. In 28 secondary epilepsies, 25 of them, brain SPECT lesions was concordant with MRI or CT lesions. 3 were disconcordant. The brain SPECT findings of generalized seizure were normal in 22 patients, diffuse irregular decreased perfusion in 8, decreased in frontal cortex in 4. temporal in 5 and frontotemporal in 3. In 45 partial seizure, 19 brain SPECT were concordant with EEG (42.4%).

  13. Chronic unpredictable stress decreases expression of brain-derived neurotrophic factor (BDNF) in mouse ovaries: relationship to oocytes developmental potential.

    Science.gov (United States)

    Wu, Li-Min; Hu, Mei-Hong; Tong, Xian-Hong; Han, Hui; Shen, Ni; Jin, Ren-Tao; Wang, Wei; Zhou, Gui-Xiang; He, Guo-Ping; Liu, Yu-Sheng

    2012-01-01

    Brain-derived neurotropic factor (BDNF) was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chronic stress affects oocytes developments, nor whether it affects expression of BDNF in ovary. Mice were randomly assigned into control group, stressed group, BDNF-treated group and BDNF-treated stressed group. The chronic unpredictable mild stress model was used to produce psychosocial stress in mice, and the model was verified by open field test and hypothalamic-pituitary-adrenal (HPA) axis activity. The methods of immunohistochemistry and western blotting were used to detect BDNF protein level and distribution. The number of retrieved oocytes, oocyte maturation, embryo cleavage and the rates of blastocyst formation after parthenogenetic activation were evaluated. Chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn't affect the BDNF expression in primordial, primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and the rate of blastocyst formation, which was rescued by exogenous BDNF treatment. BDNF in mouse ovaries may be related to the decreased number of retrieved oocytes and impaired oocytes developmental potential induced by chronic unpredictable stress.

  14. Chronic unpredictable stress decreases expression of brain-derived neurotrophic factor (BDNF in mouse ovaries: relationship to oocytes developmental potential.

    Directory of Open Access Journals (Sweden)

    Li-Min Wu

    Full Text Available BACKGROUND: Brain-derived neurotropic factor (BDNF was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chronic stress affects oocytes developments, nor whether it affects expression of BDNF in ovary. METHODS: Mice were randomly assigned into control group, stressed group, BDNF-treated group and BDNF-treated stressed group. The chronic unpredictable mild stress model was used to produce psychosocial stress in mice, and the model was verified by open field test and hypothalamic-pituitary-adrenal (HPA axis activity. The methods of immunohistochemistry and western blotting were used to detect BDNF protein level and distribution. The number of retrieved oocytes, oocyte maturation, embryo cleavage and the rates of blastocyst formation after parthenogenetic activation were evaluated. RESULTS: Chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn't affect the BDNF expression in primordial, primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and the rate of blastocyst formation, which was rescued by exogenous BDNF treatment. CONCLUSION: BDNF in mouse ovaries may be related to the decreased number of retrieved oocytes and impaired oocytes developmental potential induced by chronic unpredictable stress.

  15. Manipulation of colony environment modulates honey bee aggression and brain gene expression.

    Science.gov (United States)

    Rittschof, C C; Robinson, G E

    2013-11-01

    The social environment plays an essential role in shaping behavior for most animals. Social effects on behavior are often linked to changes in brain gene expression. In the honey bee (Apis mellifera L.), social modulation of individual aggression allows colonies to adjust the intensity with which they defend their hive in response to predation threat. Previous research has showed social effects on both aggression and aggression-related brain gene expression in honey bees, caused by alarm pheromone and unknown factors related to colony genotype. For example, some bees from less aggressive genetic stock reared in colonies with genetic predispositions toward increased aggression show both increased aggression and more aggressive-like brain gene expression profiles. We tested the hypothesis that exposure to a colony environment influenced by high levels of predation threat results in increased aggression and aggressive-like gene expression patterns in individual bees. We assessed gene expression using four marker genes. Experimentally induced predation threats modified behavior, but the effect was opposite of our predictions: disturbed colonies showed decreased aggression. Disturbed colonies also decreased foraging activity, suggesting that they did not habituate to threats; other explanations for this finding are discussed. Bees in disturbed colonies also showed changes in brain gene expression, some of which paralleled behavioral findings. These results show that bee aggression and associated molecular processes are subject to complex social influences. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  16. ELECTROENCEPHALOGRAPHY SHOWING DYING BRAIN IN A PATIENT WITH ACUTE BACLOFEN POISONING

    Directory of Open Access Journals (Sweden)

    A. Y. Mikhaylov

    2017-01-01

    Full Text Available We report a case of acute baclofen poisoning in a 23-year-old female patient, who committed suicide, which led to the development of a deep coma. The electroencephalogram on the first day recorded the phenomenon of “burst suppression”, which was seen as a sign of a dying brain. Subsequent studies have shown positive changes of the electroencephalogram and regression of neurological symptoms. Thus, the phenomenon of “burst suppression” in the depression of consciousness to deep coma and given adequate treatment, can be reversible.

  17. Differential Temporal Evolution Patterns in Brain Temperature in Different Ischemic Tissues in a Monkey Model of Middle Cerebral Artery Occlusion

    Directory of Open Access Journals (Sweden)

    Zhihua Sun

    2012-01-01

    Full Text Available Brain temperature is elevated in acute ischemic stroke, especially in the ischemic penumbra (IP. We attempted to investigate the dynamic evolution of brain temperature in different ischemic regions in a monkey model of middle cerebral artery occlusion. The brain temperature of different ischemic regions was measured with proton magnetic resonance spectroscopy (1H MRS, and the evolution processes of brain temperature were compared among different ischemic regions. We found that the normal (baseline brain temperature of the monkey brain was 37.16°C. In the artery occlusion stage, the mean brain temperature of ischemic tissue was 1.16°C higher than the baseline; however, this increase was region dependent, with 1.72°C in the IP, 1.08°C in the infarct core, and 0.62°C in the oligemic region. After recanalization, the brain temperature of the infarct core showed a pattern of an initial decrease accompanied by a subsequent increase. However, the brain temperature of the IP and oligemic region showed a monotonously and slowly decreased pattern. Our study suggests that in vivo measurement of brain temperature could help to identify whether ischemic tissue survives.

  18. Dryland biological soil crust cyanobacteria show unexpected decreases in abundance under long-term elevated CO2

    Science.gov (United States)

    Steven, Blaire; Gallegos-Graves, La Verne; Yeager, Chris M.; Belnap, Jayne; Evans, R. David; Kuske, Cheryl R.

    2012-01-01

    Biological soil crusts (biocrusts) cover soil surfaces in many drylands globally. The impacts of 10 years of elevated atmospheric CO2 on the cyanobacteria in biocrusts of an arid shrubland were examined at a large manipulated experiment in Nevada, USA. Cyanobacteria-specific quantitative PCR surveys of cyanobacteria small-subunit (SSU) rRNA genes suggested a reduction in biocrust cyanobacterial biomass in the elevated CO2 treatment relative to the ambient controls. Additionally, SSU rRNA gene libraries and shotgun metagenomes showed reduced representation of cyanobacteria in the total microbial community. Taxonomic composition of the cyanobacteria was similar under ambient and elevated CO2 conditions, indicating the decline was manifest across multiple cyanobacterial lineages. Recruitment of cyanobacteria sequences from replicate shotgun metagenomes to cyanobacterial genomes representing major biocrust orders also suggested decreased abundance of cyanobacteria sequences across the majority of genomes tested. Functional assignment of cyanobacteria-related shotgun metagenome sequences indicated that four subsystem categories, three related to oxidative stress, were differentially abundant in relation to the elevated CO2 treatment. Taken together, these results suggest that elevated CO2 affected a generalized decrease in cyanobacteria in the biocrusts and may have favoured cyanobacteria with altered gene inventories for coping with oxidative stress.

  19. Proton MRS of the peritumoral brain.

    Science.gov (United States)

    Chernov, Mikhail F; Kubo, Osami; Hayashi, Motohiro; Izawa, Masahiro; Maruyama, Takashi; Usukura, Masao; Ono, Yuko; Hori, Tomokatsu; Takakura, Kintomo

    2005-02-15

    Long-echo (TR: 2000 ms, TE: 136 ms) proton MRS of the cerebral tissue in the vicinity to intracranial lesion was done in 15 patients, mainly with parenchymal brain tumors. Significant decrease of N-acetylaspartate (NAA) (Plactate (Plactate in the lesion (Plactate in the lesion compared to perilesional brain (Plactate in the lesion is associated with lower relative NAA content in the perilesional brain tissue, independently on the presence or absence of any other factor, including brain edema (Plactate diffused from the tumor, or other metabolites secreted by lactate-producing neoplasm, should be considered as important contributors to the neuronal dysfunction in the surrounding brain. Decrease of NAA in the vicinity to intracranial lesions may reflect neuronal alteration responsible for associated epilepsy.

  20. Clinical observations of the brain abscesses, especially on the computed tomographic brain scan findings

    International Nuclear Information System (INIS)

    Kitano, Masahiko; Kuroda, Ryotaro; Yamada, Yasufumi; Yorimae, Akira; Akai, Fumiharu; Watanabe, Masaru; Nakatani, Jiro; Ioku, Masahiko

    1988-01-01

    Fifteen cases with pyogenic brain abscess were experienced in our clinic during the last 7 years. The records of these patients were examined to evaluate the clinical stage and the result of several treatments. In 12 operative cases, diagnosis was made by fluid aspirated from the abscess. Bacteria were cultured from the fluid in 5 among these cases. In 3 other non-operative patients, diagnosis was based on computed tomographic (CT) brain scans and laboratory studies. Each volume of the brain abscess and surrounding brain edema was measured on serial CT scans to evaluate the clinical stage and the abscess evolution. In symptoms and signs, it has been thought that one of the factors contributing to mortality was the level of consciousness. In this study, the disturbance of consciousness did not correlate with the size of abscess, but with that of edema. The cases reported here were divided into 3 groups according to the volume of abscess and of edema on initial CT scans. The cases of group A had small surrounding edema ( 50 ml) and small abscess ( 25 ml). The group A had slight change in the clinical status and the size of edema, but the others had severe change. Three phase changes in edema size were seen in the group B regardless of therapeutic modalities ; showing almost constant increase in first 2 weeks, great decrease in second 2 weeks and moderate decrease following these 4 weeks. In the group C, however, these phases were seen only in early operation cases. (J.P.N.)

  1. Usefulness of dynamic magnetic resonance imaging in brain tumors

    International Nuclear Information System (INIS)

    Joo, Yang Gu; Suh, Soo Jhi; Zeon, Seok Kil; Woo, Sung Ku; Kim, Hong; Kim, Jung Sik; Lee, Sung Moon; Lee, Hee Jung; Takahashi, Mutsumasa

    1994-01-01

    To investigate the usefulness of dynamic MR imaging in the differential diagnosis of brain tumors. Dynamic MR imaging was performed in 43 patients with histopathologically proved brain tumors. Serial images were sequentially obtained every 30 seconds for 3-5 minutes with use of spin-echo technique(TR 200msec/TE 15msec) after rapid injection of Gd-DTPA in a dose of 0.1mmol/kg body weight. Dynamics of contrast enhancement of the brain tumors were analyzed visually and by the sequential contrast enhancement ratio(CER). On the dynamic MR imaging, contrast enhancement pattern of the gliomas showed gradual increase in signal intensity(SI) till 180 seconds and usually had a longer time to peak of the CER. The SI of metastatic brain tumors increased steeply till 30 seconds and then rapidly or gradually decreased and the tumors had a shorter time to peak of the CER. Meningiomas showed a rapid ascent in SI till 30 to 60 seconds and then made a plateau or slight descent of the CER. Lymphomas and germinomas showed relatively rapid increase of SI till 30 seconds and usually had a longer time peak of the CER. Dynamic MR imaging with Gd-DTPA may lead to further information about the brain tumors as the sequential contrast enhancement pattern and CER parameters seem to be helpful in discriminating among the brain tumors

  2. Increased radial glia quiescence, decreased reactivation upon injury and unaltered neuroblast behavior underlie decreased neurogenesis in the aging zebrafish telencephalon.

    Science.gov (United States)

    Edelmann, Kathrin; Glashauser, Lena; Sprungala, Susanne; Hesl, Birgit; Fritschle, Maike; Ninkovic, Jovica; Godinho, Leanne; Chapouton, Prisca

    2013-09-01

    The zebrafish has recently become a source of new data on the mechanisms of neural stem cell (NSC) maintenance and ongoing neurogenesis in adult brains. In this vertebrate, neurogenesis occurs at high levels in all ventricular regions of the brain, and brain injuries recover successfully, owing to the recruitment of radial glia, which function as NSCs. This new vertebrate model of adult neurogenesis is thus advancing our knowledge of the molecular cues in use for the activation of NSCs and fate of their progeny. Because the regenerative potential of somatic stem cells generally weakens with increasing age, it is important to assess the extent to which zebrafish NSC potential decreases or remains unaltered with age. We found that neurogenesis in the ventricular zone, in the olfactory bulb, and in a newly identified parenchymal zone of the telencephalon indeed declines as the fish ages and that oligodendrogenesis also declines. In the ventricular zone, the radial glial cell population remains largely unaltered morphologically but enters less frequently into the cell cycle and hence produces fewer neuroblasts. The neuroblasts themselves do not change their behavior with age and produce the same number of postmitotic neurons. Thus, decreased neurogenesis in the physiologically aging zebrafish brain is correlated with an increasing quiescence of radial glia. After injuries, radial glia in aged brains are reactivated, and the percentage of cell cycle entry is increased in the radial glia population. However, this reaction is far less pronounced than in younger animals, pointing to irreversible changes in aging zebrafish radial glia. Copyright © 2013 Wiley Periodicals, Inc.

  3. Boosting Memory by tDCS to Frontal or Parietal Brain Regions? A Study of the Enactment Effect Shows No Effects for Immediate and Delayed Recognition

    Directory of Open Access Journals (Sweden)

    Beat Meier

    2018-06-01

    Full Text Available Boosting memory with transcranial direct current stimulation (tDCS seems to be an elegant way to optimize learning. Here we tested whether tDCS to the left dorsolateral prefrontal cortex or to the left posterior parietal cortex would boost recognition memory in general and/or particularly for action phrases enacted at study. During study, 48 young adults either read or enacted simple action phrases. Memory for the action phrases was assessed after a retention interval of 45 min and again after 7-days to investigate the long-term consequences of brain stimulation. The results showed a robust enactment effect in both test sessions. Moreover, the decrease in performance was more pronounced for reading than for enacting the phrases at study. However, tDCS did not reveal any effect on subsequent recognition memory performance. We conclude that memory benefits of tDCS are not easily replicated. In contrast, enactment at study reliably boosts subsequent memory.

  4. Decreased hedonic responsiveness following chronic mild stress is not secondary to loss of body weight.

    Science.gov (United States)

    Willner, P; Moreau, J L; Nielsen, C K; Papp, M; Sluzewska, A

    1996-07-01

    Chronic exposure to mild unpredictable stress (CMS) has previously been found to decrease hedonic responsiveness, as measured by the consumption of palatable sweet solutions or sensitivity to brain stimulation reward. These effects are reversed by chronic treatment with antidepressant drugs, and the CMS procedure has been proposed as a relatively valid animal model of depression. It has recently been suggested that the behavioural effects of CMS may be secondary to loss of body weight. This article collates data from five laboratories using the CMS procedure. Data are presented from seven studies using five different rat strains, as well as CD1 mice. Three-week exposure to CMS significantly decreased sucrose consumption by Lister hooded, PVG hooded, Wistar, and Wistar WU rats, and by CD1 mice, and sensitivity to brain stimulation reward in Ibm:Ro Ro rats. Weight loss in different experiments varied between 0 and 10%. Hedonic sensitivity relative to body weight (e.g., mg sucrose/g body weight) decreased significantly in all experiments. Animals maintained on a restricted feeding regime lost weight but did not show decreases in sucrose intake. It is concluded that decreased hedonic sensitivity following chronic mild stress cannot be attributed to loss of body weight.

  5. Protease-resistant prions selectively decrease Shadoo protein.

    Directory of Open Access Journals (Sweden)

    Joel C Watts

    2011-11-01

    Full Text Available The central event in prion diseases is the conformational conversion of the cellular prion protein (PrP(C into PrP(Sc, a partially protease-resistant and infectious conformer. However, the mechanism by which PrP(Sc causes neuronal dysfunction remains poorly understood. Levels of Shadoo (Sho, a protein that resembles the flexibly disordered N-terminal domain of PrP(C, were found to be reduced in the brains of mice infected with the RML strain of prions [1], implying that Sho levels may reflect the presence of PrP(Sc in the brain. To test this hypothesis, we examined levels of Sho during prion infection using a variety of experimental systems. Sho protein levels were decreased in the brains of mice, hamsters, voles, and sheep infected with different natural and experimental prion strains. Furthermore, Sho levels were decreased in the brains of prion-infected, transgenic mice overexpressing Sho and in infected neuroblastoma cells. Time-course experiments revealed that Sho levels were inversely proportional to levels of protease-resistant PrP(Sc. Membrane anchoring and the N-terminal domain of PrP both influenced the inverse relationship between Sho and PrP(Sc. Although increased Sho levels had no discernible effect on prion replication in mice, we conclude that Sho is the first non-PrP marker specific for prion disease. Additional studies using this paradigm may provide insight into the cellular pathways and systems subverted by PrP(Sc during prion disease.

  6. Effect of naloxone hydrochloride on c-fos protein expression in brain and plasma beta-endorphin level in rats with diffuse brain injury and secondary brain insult

    Directory of Open Access Journals (Sweden)

    Jun-jie JING

    2012-09-01

    Full Text Available Objective To observe the changes of c-fos protein expression in brain and beta-endorphin (β-EP level in blood plasma in rats with diffuse brain injury (DBI and secondary brain insult (SBI after intraperitoneal injection of naloxone hydrochloride, and explore the role of c-fos andβ-EP in development of SBI in rats. Methods Seventy health male SD rats were enrolled in the present study and randomly divided into group A (intraperitoneally injected with 0.9% saline after DBI and SBI model was reproduced, group B (injected intraperitoneally with 1.0mg/kg naloxone hydrochloride after DBI and SBI model was reproduced, and group C (intraperitoneally injected with 1.0mg/kg naloxone hydrochloride after DBI and before SBI model was reproduced. The animals were sacrificed 3, 24 and 48 hours after injury, and the number of c-fos positive cells in brain and content of β-EP in blood plasma were determined by immunohistochemistry and radioimmunoassay respectively, the water content and number of injured neurons in brain tissue were measured by pathomorphological observation of the brain tissue. Results No significant difference was observed between group B and C for all the detection parameters. In group B and C, the water content in brain tissue at 3h and 24h was found to be decreased, while the number of injured neurons at 24h and 48h increased, number of c-fos positive cells in brain at 3h, 24h and 48h decreased, and content of β-EP in blood plasma at 3h and 24h decreased when compared with group A(P < 0.05. Conclusion Naloxone hydrochloride could decrease the c-fos expression in brain and β-EP level in blood plasma, alleviate the nerve injury, and protect neural function. The therapeutic effect of naloxone administered either after DBI and SBI or after DBI and before SBI was similar.

  7. Brain CT scan in acute carbon monoxide poisoning

    International Nuclear Information System (INIS)

    We, En-Huei

    1986-01-01

    The brain CT findings in 19 patients with acute carbon monoxide poisoning was analysed and the emphasis was placed on the relationship between CT findings and prognosis. Five had a normal manifestation in CT ; eight had the findings of ovoid or patchy low density area in globus pallidus, bilateral or unlateral, during the second day to fifth week after poisoning, and the low density areas were decreasing and blurring in edge in follow up and at last disappeared during 3 - 14 weeks in three cases of them ; nine showed the appearance of diffuse low density of white matter and of globus pallidus in some of them ; two had an appearance of brain atrophy. The pathology of CT findings mentioned above may be brain edema, necrosis, malacia and degeneration in gray matter and globus pallidus. The result suggested the cases with normal CT manifestation, cerebral edema and decreasing and disappearing low density area had a good prognosis, in contrary, the cases with persistant low density in globus pallidus had a poorer prognosis. (author)

  8. Decrease in early right alpha band phase synchronization and late gamma band oscillations in processing syntax in music.

    Science.gov (United States)

    Ruiz, María Herrojo; Koelsch, Stefan; Bhattacharya, Joydeep

    2009-04-01

    The present study investigated the neural correlates associated with the processing of music-syntactical irregularities as compared with regular syntactic structures in music. Previous studies reported an early ( approximately 200 ms) right anterior negative component (ERAN) by traditional event-related-potential analysis during music-syntactical irregularities, yet little is known about the underlying oscillatory and synchronization properties of brain responses which are supposed to play a crucial role in general cognition including music perception. First we showed that the ERAN was primarily represented by low frequency (music-syntactical irregularities as compared with music-syntactical regularities, were associated with (i) an early decrease in the alpha band (9-10 Hz) phase synchronization between right fronto-central and left temporal brain regions, and (ii) a late ( approximately 500 ms) decrease in gamma band (38-50 Hz) oscillations over fronto-central brain regions. These results indicate a weaker degree of long-range integration when the musical expectancy is violated. In summary, our results reveal neural mechanisms of music-syntactic processing that operate at different levels of cortical integration, ranging from early decrease in long-range alpha phase synchronization to late local gamma oscillations. 2008 Wiley-Liss, Inc.

  9. Role of hypotension in decreasing cerebral blood flow in porcine endotoxemia

    International Nuclear Information System (INIS)

    Miller, C.F.; Breslow, M.J.; Shapiro, R.M.; Traystman, R.J.

    1987-01-01

    The role of reduced arterial blood pressure (MAP) in decreasing cerebral blood flow (CBF) during endotoxemia was studied in pentobarbital-anesthetized pigs. Microspheres were used to measure regional CBF changes during MAP manipulations in animals with and without endotoxin. Endotoxin decreased MAP to 50 mmHg and decreased blood flow to the cortex and cerebellum without affecting cerebral cortical oxygen consumption (CMRo 2 ). Elevating MAP from 50 to 70 mmHg during endotoxemia with norepinephrine did not change cortical blood flow or CMRo 2 but increased cerebellar blood flow. Brain stem blood flow was not affected by endotoxin or norepinephrine. When MAP was decreased to 50 mmHg by hemorrhage without endotoxin, no change in blood flow to cortex, cerebellum, or brain stem was observed from base-line levels. These results suggest that decreased MAP below a lower limit for cerebral autoregulation does not account for the decreased CBF observed after endotoxin

  10. Meta-analysis of diffusion tensor imaging studies shows altered fractional anisotropy occurring in distinct brain areas in association with depression.

    LENUS (Irish Health Repository)

    Murphy, Melissa L

    2011-09-01

    Fractional anisotropy anomalies occurring in the white matter tracts in the brains of depressed patients may reflect microstructural changes underlying the pathophysiology of this disorder. We conducted a meta-analysis of fractional anisotropy abnormalities occurring in major depressive disorder using voxel-based diffusion tensor imaging studies. Using the Embase, PubMed and Google Scholar databases, 89 relevant data sets were identified, of which 7 (including 188 patients with major depressive disorder and 221 healthy controls) met our inclusion criteria. Authors were contacted to retrieve any additional data required. Coordinates were extracted from clusters of significant white matter fractional anisotropy differences between patients and controls. Relevant demographic, clinical and methodological variables were extracted from each study or obtained directly from authors. The meta-analysis was carried out using Signed Differential Mapping. Patients with depression showed decreased white matter fractional anisotropy values in the superior longitudinal fasciculus and increased fractional anisotropy values in the fronto-occipital fasciculus compared to controls. Using quartile and jackknife sensitivity analysis, we found that reduced fractional anisotropy in the left superior longitudinal fasciculus was very stable, with increases in the right fronto-occipital fasciculus driven by just one study. In conclusion, our meta-analysis revealed a significant reduction in fractional anisotropy values in the left superior longitudinal fasciculus, which may ultimately play an important role in the pathology of depression.

  11. Effect of ethanol on γ-aminobutyric acid in the brain

    International Nuclear Information System (INIS)

    Lassanova, M.; Tursky, T.; Homerova, D.

    1989-01-01

    The effect of acute and chronic ethanol administration on the level of γ-aminobutyric acid (GABA), glutamate, aspartate, and glutamine was investigated using 14 C-labelled compounds. The level of GABA rose after both acute and chronic ethanol administration. In chronic experiments also the levels of glutamate, aspartate and glutamine were increased. In acute experiments the incorporation from glucose into the studied amino acids (neuronal compartment) increased, while in chronic experiments a decreasing trend was observed. In the glial compartment the incorporation increased only into glutamate and glutamine in acute experiments, while in chronic experiments a decreased incorporation into glutamine was recorded. The activities of three enzymes were studied in seven parts of the brain after acute ethanol administration. The activity of glutamic acid decarboxylase increased in the hypothalamus and brain cortex and decreased in the medulla oblongata. The activity of GABA transaminase did not change and the activity of glutamine synthetase decreased only in the hippocampus. In accordance with several other studies, the presented results show that ethanol interferes with the GABA system in the brain. It is suggested that the primary effect of ethanol is exerted on the cell membranes with preference for the regions connected with the GABA system. (author). 3 figs., 6 tabs., 18 refs

  12. Brain lesion correlates of fatigue in individuals with traumatic brain injury.

    Science.gov (United States)

    Schönberger, Michael; Reutens, David; Beare, Richard; O'Sullivan, Richard; Rajaratnam, Shantha M W; Ponsford, Jennie

    2017-10-01

    The purpose of this study was to investigate the neurological correlates of both subjective fatigue as well as objective fatigability in individuals with traumatic brain injury (TBI). The study has a cross-sectional design. Participants (N = 53) with TBI (77% male, mean age at injury 38 years, mean time since injury 1.8 years) underwent a structural magnetic resonance imaging (MRI) scan and completed the Fatigue Severity Scale (FSS), while a subsample (N = 36) was also tested with a vigilance task. While subjective fatigue (FSS) was not related to measures of brain lesions, multilevel analyses showed that a change in the participants' decision time was significantly predicted by grey matter (GM) lesions in the right frontal lobe. The time-dependent development of the participants' error rate was predicted by total brain white matter (WM) lesion volumes, as well as right temporal GM and WM lesion volumes. These findings could be explained by decreased functional connectivity of attentional networks, which results in accelerated exhaustion during cognitive task performance. The disparate nature of objectively measurable fatigability on the one hand and the subjective experience of fatigue on the other needs further investigation.

  13. The effect of perinatal 60Co gamma radiation on brain weight in beagles

    International Nuclear Information System (INIS)

    Hamilton, B.F.; Benjamin, S.A.; Angleton, G.M.; Lee, A.C.

    1989-01-01

    Beagle dogs were given single, whole-body 60 Co gamma-radiation exposures at one of three prenatal (8, 28, or 55 days postcoitus) or three postnatal (2, 70, or 365 days postpartum) ages to evaluate the relative radiosensitivity of various stages of brain development. A total of 387 dogs received mean doses ranging from 0.16 to 3.83 Gy, and 120 dogs were sham-irradiated. Groups of dogs were sacrificed at preselected times from 70 days to 11 years of age. Brain weight decreased significantly with increasing dose in dogs irradiated at 28 or 55 days postcoitus or at 2 days postpartum. Irradiations at 28 days postcoitus were dramatically more effective in causing a reduction in brain weight than those at 55 days postcoitus or 2 days postpartum. Among dogs given 1.0 Gy or more and followed for up to 4 years, there was a radiation effect evident at all three sensitive exposure ages. Among dogs given lower doses and followed for up to 11 years, there was a significant decrease in brain weight in dogs given 0.80-0.88 Gy at 28 days postcoitus. All decreases in brain weight were present after normalization for radiation-induced reductions in skeletal (body) size. No specific morphologic changes were noted in the brains which showed the radiation-related reductions in size

  14. Modulation of brain glutamate dehydrogenase as a tool for controlling seizures

    Directory of Open Access Journals (Sweden)

    Rasgado Lourdes A. Vega

    2015-12-01

    Full Text Available Glutamate (Glu is a major excitatory neurotransmitter involved in epilepsy. Glu is synthesized by glutamate dehydrogenase (GDH, E.C. 1.4.1.3 and dysfunction of the enzymatic activity of GDH is associated with brain pathologies. The main goal of this work is to establish the role of GDH in the effects of antiepileptic drugs (AEDs such as valproate (VALP, diazepam (DIAZ and diphenylhydantoin (DPH and its repercussions on oxygen consumption. Oxidative deamination of Glu and reductive amination of aketoglutarate (αK in mice brain were investigated. Our results show that AEDs decrease GDH activity and oxygen consumption in vitro. In ex vivo experiments, AEDs increased GDH activity but decreased oxygen consumption during Glu oxidative deamination. VALP and DPH reversed the increase in reductive amination of αK caused by the chemoconvulsant pentylenetetrazol. These results suggest that AEDs act by modulating brain GDH activity, which in turn decreased oxygen consumption. GDH represents an important regulation point of neuronal excitability, and modulation of its activity represents a potential target for metabolic treatment of epilepsy and for the development of new AEDs.

  15. Effect of steroid on brain tumors and surround edemas : observation with regional cerebral blood volume (rCBV) maps of perfusion MRI

    International Nuclear Information System (INIS)

    Choi, Ju Youl; Sun, Joo Sung; Kim, Sun Yong; Kim, Ji Hyung; Suh, Jung Ho; Cho, Kyung Gi; Kim, Jang Sung

    2000-01-01

    To observe the hemodynamic change in brain tumors and peritumoral edemas after steroid treatment, and then investigate the clinical usefulness of perfusion MRI. We acquired conventional and perfusion MR images in 15 patients with various intracranial tumors (4 glioblastoma multiformes, 4 meningiomas, 3 metastatic tumors, 1 anaplastic ependymoma, 1 anaplastic astrocytoma, 1 hemangioblastoma, and 1 pilocytic astrocytoma). For perfusion MR imaging, a 1.5T unit employing the gradient-echo EPI technique was used, and further perfusion MR images were obtained 2-10 days after intravenous steroid therapy. After processing of the raw data, regional cerebral blood volume (rCBV) maps were reconstructed. The maps were visually evaluated by comparing relative perfusion in brain tumors and peritumoral edemas with that in contralateral white matter. Objective evaluations were performed by comparing the perfusion ratios of brain tumors and peritumoral edemas. Visual evaluations of rCBV maps, showed that in most brain tumors (67%, 10/15), perfusion was high before steroid treatment and showed in (80%, 12/15) decreased afterwards. Objective evaluation, showed that in all brain tumors, perfusion decreased. Visual evaluation of perfusion change in peritumoral edemas revealed change in only one case, but objective evaluation indicated that perfusion decreased significantly in all seven cases. rCBV maps acquired by perfusion MR imaging can provide hemodynamic information about brain tumors and peritumoral edemas. Such maps could prove helpful in the preoperative planning of brain tumor surgery and the monitoring of steroid effects during conservative treatment. (author)

  16. Pax6 interacts with Iba1 and shows age-associated alterations in brain of aging mice.

    Science.gov (United States)

    Maurya, Shashank Kumar; Mishra, Rajnikant

    2017-07-01

    The Pax6, a transcriptional regulator and multifunctional protein, has been found critical for neurogenesis, neuro-degeneration, mental retardation, neuroendocrine tumors, glioblastoma and astrocytomas. The age-associated alteration in the expression of Pax6 in neuron and glia has also been observed in the immunologically privileged brain. Therefore, it is presumed that Pax6 may modulate brain immunity by activation of microglia either directly interacting with genes or proteins of microglia or indirectly though inflammation associated with neurodegeneration. This report describes evaluation of expression, co-localization and interactions of Pax6 with Ionized binding protein1 (Iba1) in brain of aging mice by Immunohistochemistry, Chromatin Immuno-precipitation (ChIP) and Co-immunoprecipitation (Co-IP), respectively. The co-localization of Pax6 with Iba1 was observed in the cerebellum, cerebral cortex, hippocampus, midbrain and olfactory lobe. The Pax6 and Iba1 also interact physically. The age-dependent alteration in their expression and co-localization were also observed in mice. Results indicate Pax6-dependent activities of Iba1 in the remodelling of microglia during immunological surveillance of the brain. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. cAMP and forskolin decrease γ-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes

    International Nuclear Information System (INIS)

    Heuschneider, G.; Schwartz, R.D.

    1989-01-01

    The effects of the cyclic nucleotide cAMP on γ-aminobutyric acid-gated chloride channel function were investigated. The membrane-permeant cAMP analog N 6 , O 2' -dibutyryladenosine 3',5'-cyclic monophosphate inhibited muscimol-induced 36 Cl - uptake into rat cerebral cortical synaptoneurosomes in a concentration-dependent manner. The inhibition was due to a decrease in the maximal effect of muscimol, with no change in potency. Similar effects were observed with 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, 8-bromoadenosine 3',5'-cyclic monophosphate, and the phosphodiesterase inhibitor isobutylmethylxanthine. The effect of endogenous cAMP accumulation on the γ-aminobutyric acid-gated Cl - channel was studied with forskolin, an activator of adenylate cyclase. Under identical conditions, in the intact synaptoneurosomes, forskolin inhibited muscimol-induced 36 Cl - uptake and generated cAMP with similar potencies. Surprisingly, 1,9-dideoxyforskolin, which does not activate adenylate cyclase, also inhibited the muscimol response, suggesting that forskolin and its lipophilic derivatives may interact with the Cl - channel directly. The data suggest that γ-aminobutyric acid (GABA A ) receptor function in brain can be regulated by cAMP-dependent phosphorylation

  18. Brain core temperature of patients with mild traumatic brain injury as assessed by DWI-thermometry

    International Nuclear Information System (INIS)

    Tazoe, Jun; Yamada, Kei; Akazawa, Kentaro; Sakai, Koji; Mineura, Katsuyoshi

    2014-01-01

    The aim of this study was to assess the brain core temperature of patients with mild traumatic brain injury (mTBI) using a noninvasive temperature measurement technique based on the diffusion coefficient of the cerebrospinal fluid. This retrospective study used the data collected from April 2008 to June 2011. The patient group comprised 20 patients with a Glasgow Coma Scale score of 14 or 15 who underwent magnetic resonance imaging within 30 days after head trauma. The normal control group comprised 14 subjects who volunteered for a brain checkup (known in Japan as ''brain dock''). We compared lateral ventricular (LV) temperature between patient and control groups. Follow-up studies were performed for four patients. LV temperature measurements were successfully performed for both patients and controls. Mean (±standard deviation) measured LV temperature was 36.9 ± 1.5 C in patients, 38.7 ± 1.8 C in follow-ups, and 37.9 ± 1.2 C in controls, showing a significant difference between patients and controls (P = 0.017). However, no significant difference was evident between patients and follow-ups (P = 0.595) or between follow-ups and controls (P = 0.465). A reduction in brain core temperature was observed in patients with mTBI, possibly due to a global decrease in metabolism. (orig.)

  19. Structural whole-brain covariance of the anterior and posterior hippocampus: Associations with age and memory.

    Science.gov (United States)

    Nordin, Kristin; Persson, Jonas; Stening, Eva; Herlitz, Agneta; Larsson, Elna-Marie; Söderlund, Hedvig

    2018-02-01

    The hippocampus (HC) interacts with distributed brain regions to support memory and shows significant volume reductions in aging, but little is known about age effects on hippocampal whole-brain structural covariance. It is also unclear whether the anterior and posterior HC show similar or distinct patterns of whole-brain covariance and to what extent these are related to memory functions organized along the hippocampal longitudinal axis. Using the multivariate approach partial least squares, we assessed structural whole-brain covariance of the HC in addition to regional volume, in young, middle-aged and older adults (n = 221), and assessed associations with episodic and spatial memory. Based on findings of sex differences in both memory and brain aging, we further considered sex as a potential modulating factor of age effects. There were two main covariance patterns: one capturing common anterior and posterior covariance, and one differentiating the two regions by capturing anterior-specific covariance only. These patterns were differentially related to associative memory while unrelated to measures of single-item memory and spatial memory. Although patterns were qualitatively comparable across age groups, participants' expression of both patterns decreased with age, independently of sex. The results suggest that the organization of hippocampal structural whole-brain covariance remains stable across age, but that the integrity of these networks decreases as the brain undergoes age-related alterations. © 2017 Wiley Periodicals, Inc.

  20. Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and Kinetics in the Rat Brain.

    Science.gov (United States)

    Hsieh, Ya-Ju; Wu, Liang-Chih; Ke, Chien-Chih; Chang, Chi-Wei; Kuo, Jung-Wen; Huang, Wen-Sheng; Chen, Fu-Du; Yang, Bang-Hung; Tai, Hsiao-Ting; Chen, Sharon Chia-Ju; Liu, Ren-Shyan

    2018-02-01

    Ethanol (EtOH) intoxication inhibits glucose transport and decreases overall brain glucose metabolism; however, humans with long-term EtOH consumption were found to have a significant increase in [1- 11 C]-acetate uptake in the brain. The relationship between the cause and effect of [1- 11 C]-acetate kinetics and acute/chronic EtOH intoxication, however, is still unclear. [1- 11 C]-acetate positron emission tomography (PET) with dynamic measurement of K 1 and k 2 rate constants was used to investigate the changes in acetate metabolism in different brain regions of rats with acute or chronic EtOH intoxication. PET imaging demonstrated decreased [1- 11 C]-acetate uptake in rat brain with acute EtOH intoxication, but this increased with chronic EtOH intoxication. Tracer uptake rate constant K 1 and clearance rate constant k 2 were decreased in acutely intoxicated rats. No significant change was noted in K 1 and k 2 in chronic EtOH intoxication, although 6 of 7 brain regions showed slightly higher k 2 than baseline. These results indicate that acute EtOH intoxication accelerated acetate transport and metabolism in the rat brain, whereas chronic EtOH intoxication status showed no significant effect. In vivo PET study confirmed the modulatory role of EtOH, administered acutely or chronically, in [1- 11 C]-acetate kinetics and metabolism in the rat brain. Acute EtOH intoxication may inhibit the transport and metabolism of acetate in the brain, whereas chronic EtOH exposure may lead to the adaptation of the rat brain to EtOH in acetate utilization. [1- 11 C]-acetate PET imaging is a feasible approach to study the effect of EtOH on acetate metabolism in rat brain. Copyright © 2017 by the Research Society on Alcoholism.

  1. Nuclear Receptor TLX Regulates Cell Cycle Progression in Neural Stem Cells of the Developing Brain

    OpenAIRE

    Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

    2007-01-01

    TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal ...

  2. Functional connectivity of the rodent brain using optical imaging

    Science.gov (United States)

    Guevara Codina, Edgar

    The aim of this thesis is to apply functional connectivity in a variety of animal models, using several optical imaging modalities. Even at rest, the brain shows high metabolic activity: the correlation in slow spontaneous fluctuations identifies remotely connected areas of the brain; hence the term "functional connectivity". Ongoing changes in spontaneous activity may provide insight into the neural processing that takes most of the brain metabolic activity, and so may provide a vast source of disease related changes. Brain hemodynamics may be modified during disease and affect resting-state activity. The thesis aims to better understand these changes in functional connectivity due to disease, using functional optical imaging. The optical imaging techniques explored in the first two contributions of this thesis are Optical Imaging of Intrinsic Signals and Laser Speckle Contrast Imaging, together they can estimate the metabolic rate of oxygen consumption, that closely parallels neural activity. They both have adequate spatial and temporal resolution and are well adapted to image the convexity of the mouse cortex. In the last article, a depth-sensitive modality called photoacoustic tomography was used in the newborn rat. Optical coherence tomography and laminar optical tomography were also part of the array of imaging techniques developed and applied in other collaborations. The first article of this work shows the changes in functional connectivity in an acute murine model of epileptiform activity. Homologous correlations are both increased and decreased with a small dependence on seizure duration. These changes suggest a potential decoupling between the hemodynamic parameters in resting-state networks, underlining the importance to investigate epileptic networks with several independent hemodynamic measures. The second study examines a novel murine model of arterial stiffness: the unilateral calcification of the right carotid. Seed-based connectivity analysis

  3. A Right Brain/Left Brain Model of Acting.

    Science.gov (United States)

    Bowlen, Clark

    Using current right brain/left brain research, this paper develops a model that explains acting's underlying quality--the actor is both himself and the character. Part 1 presents (1) the background of the right brain/left brain theory, (2) studies showing that propositional communication is a left hemisphere function while affective communication…

  4. Network-dependent modulation of brain activity during sleep.

    Science.gov (United States)

    Watanabe, Takamitsu; Kan, Shigeyuki; Koike, Takahiko; Misaki, Masaya; Konishi, Seiki; Miyauchi, Satoru; Miyahsita, Yasushi; Masuda, Naoki

    2014-09-01

    Brain activity dynamically changes even during sleep. A line of neuroimaging studies has reported changes in functional connectivity and regional activity across different sleep stages such as slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. However, it remains unclear whether and how the large-scale network activity of human brains changes within a given sleep stage. Here, we investigated modulation of network activity within sleep stages by applying the pairwise maximum entropy model to brain activity obtained by functional magnetic resonance imaging from sleeping healthy subjects. We found that the brain activity of individual brain regions and functional interactions between pairs of regions significantly increased in the default-mode network during SWS and decreased during REM sleep. In contrast, the network activity of the fronto-parietal and sensory-motor networks showed the opposite pattern. Furthermore, in the three networks, the amount of the activity changes throughout REM sleep was negatively correlated with that throughout SWS. The present findings suggest that the brain activity is dynamically modulated even in a sleep stage and that the pattern of modulation depends on the type of the large-scale brain networks. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Clinical applications of brain perfusion imaging with sup 99m Tc-HM-PAO

    Energy Technology Data Exchange (ETDEWEB)

    Xiangtong, Lin [Shanghai Medical Univ. (China). Huashan Hospital; and others

    1989-11-01

    200 patients with central nervous system diseases were studied with {sup 99m}Tc-HM-PAO and SPECT, including Parkinson's disease (PD) 47, Vascular headache 69, CVD 34, Epilepsy 26, Head truma 10, Brain tumor 5 and other 9 cases. Part of them have been compared with the results of MRI, X-CT and EEG. The positivity of SPECT in PD is 61.7% with decrease perfusion in local area of cerebram and basal ganglia and only 4 cases had lower perfusion in cerebellum; in headache is 46.4%, showing variable perfusion patterns; in CVD is 79.4% with decrease perfusion, luxury perfusion and the phenomenon of 'diaschsis'. In epilepsy, the abnormal foci mostly localize in temporal lobe and have close relation to the results of EEG. In brain tumor it also denotes decreased uptake of tracer. The clinicl singnificance of brain perfusion imaging with {sup 99m}Tc-HM-PAO was discussed.

  6. Cognitive benefit and cost of acute stress is differentially modulated by individual brain state

    Science.gov (United States)

    Hermans, Erno J.; Fernández, Guillén

    2017-01-01

    Abstract Acute stress is associated with beneficial as well as detrimental effects on cognition in different individuals. However, it is not yet known how stress can have such opposing effects. Stroop-like tasks typically show this dissociation: stress diminishes speed, but improves accuracy. We investigated accuracy and speed during a stroop-like task of 120 healthy male subjects after an experimental stress induction or control condition in a randomized, counter-balanced cross-over design; we assessed brain–behavior associations and determined the influence of individual brain connectivity patterns on these associations, which may moderate the effect and help identify stress resilience factors. In the mean, stress was associated to increase in accuracy, but decrease in speed. Accuracy was associated to brain activation in a distributed set of brain regions overlapping with the executive control network (ECN) and speed to temporo-parietal activation. In line with a stress-related large-scale network reconfiguration, individuals showing an upregulation of the salience and down-regulation of the executive-control network under stress displayed increased speed, but decreased performance. In contrast, individuals who upregulate their ECN under stress show improved performance. Our results indicate that the individual large-scale brain network balance under acute stress moderates cognitive consequences of threat. PMID:28402480

  7. Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier.

    Science.gov (United States)

    Couch, Jessica A; Yu, Y Joy; Zhang, Yin; Tarrant, Jacqueline M; Fuji, Reina N; Meilandt, William J; Solanoy, Hilda; Tong, Raymond K; Hoyte, Kwame; Luk, Wilman; Lu, Yanmei; Gadkar, Kapil; Prabhu, Saileta; Ordonia, Benjamin A; Nguyen, Quyen; Lin, Yuwen; Lin, Zhonghua; Balazs, Mercedesz; Scearce-Levie, Kimberly; Ernst, James A; Dennis, Mark S; Watts, Ryan J

    2013-05-01

    Bispecific antibodies using the transferrin receptor (TfR) have shown promise for boosting antibody uptake in brain. Nevertheless, there are limited data on the therapeutic properties including safety liabilities that will enable successful development of TfR-based therapeutics. We evaluate TfR/BACE1 bispecific antibody variants in mouse and show that reducing TfR binding affinity improves not only brain uptake but also peripheral exposure and the safety profile of these antibodies. We identify and seek to address liabilities of targeting TfR with antibodies, namely, acute clinical signs and decreased circulating reticulocytes observed after dosing. By eliminating Fc effector function, we ameliorated the acute clinical signs and partially rescued a reduction in reticulocytes. Furthermore, we show that complement mediates a residual decrease in reticulocytes observed after Fc effector function is eliminated. These data raise important safety concerns and potential mitigation strategies for the development of TfR-based therapies that are designed to cross the blood-brain barrier.

  8. Citric acid effects on brain and liver oxidative stress in lipopolysaccharide-treated mice.

    Science.gov (United States)

    Abdel-Salam, Omar M E; Youness, Eman R; Mohammed, Nadia A; Morsy, Safaa M Youssef; Omara, Enayat A; Sleem, Amany A

    2014-05-01

    Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-α) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-α, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

  9. Effect of maternal excessive sodium intake on postnatal brain development in rat offspring.

    Science.gov (United States)

    Shin, Jung-a; Ahn, Young-mo; Lee, Hye-ah; Park, Hyesook; Kim, Young-ju; Lee, Hwa-young

    2015-04-01

    Postnatal brain development is affected by the in utero environment. Modern people usually have a high sodium intake. The aim of this study was to investigate the effect of sodium hyperingestion during pregnancy on the postnatal brain development of rat offspring. The sodium-overloaded rats received 1.8% NaCl in their drinking water for 7 days during the last week of gestation. Their body weight, urine, and blood levels of sodium and other parameters were measured. Some rats were sacrificed at pregnancy day 22 and the weight and length of the placenta and foetus were measured. The cerebral cortex and hippocampus were obtained from their offspring at postnatal day 1 and at postnatal weeks 1, 2, 4, and 8. Western blot analyses were conducted with brain tissue lysates. The sodium-overloaded animals had decreased weight gain in the last week of gestation as well as decreased food intake, increased water intake, urine volume, urine sodium, and serum sodium. There were no differences in placental weight and length. The foetuses of sodium-overloaded rats showed decreased body weight and size, and this difference was maintained postnatally for 2 weeks. In the cerebral cortex and hippocampus of the offspring, the protein levels of myelin basic protein, calmodulin/calcium-dependent protein kinase II, and brain-derived neurotrophic factor were decreased or aberrantly expressed. The present data suggest that increased sodium intake during pregnancy affects the brain development of the offspring.

  10. Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment

    Directory of Open Access Journals (Sweden)

    Donna H. Murrell

    2016-06-01

    Full Text Available INTRODUCTION: The incidence of brain metastasis due to breast cancer is increasing, and prognosis is poor. Treatment is challenging because the blood-brain barrier (BBB limits efficacy of systemic therapies. In this work, we develop a clinically relevant whole brain radiotherapy (WBRT plan to investigate the impact of radiation on brain metastasis development and BBB permeability in a murine model. We hypothesize that radiotherapy will decrease tumor burden and increase tumor permeability, which could offer a mechanism to increase drug uptake in brain metastases. METHODS: Contrast-enhanced magnetic resonance imaging (MRI and high-resolution anatomical MRI were used to evaluate BBB integrity associated with brain metastases due to breast cancer in the MDA-MB-231-BR-HER2 model during their natural development. Novel image-guided microirradiation technology was employed to develop WBRT treatment plans and to investigate if this altered brain metastatic growth or permeability. Histology and immunohistochemistry were performed on whole brain slices corresponding with MRI to validate and further investigate radiological findings. RESULTS: Herein, we show successful implementation of microirradiation technology that can deliver WBRT to small animals. We further report that WBRT following diagnosis of brain metastasis can mitigate, but not eliminate, tumor growth in the MDA-MB-231-BR-HER2 model. Moreover, radiotherapy did not impact BBB permeability associated with metastases. CONCLUSIONS: Clinically relevant WBRT is not curative when delivered after MRI-detectable tumors have developed in this model. A dose of 20 Gy in 2 fractions was not sufficient to increase tumor permeability such that it could be used as a method to increase systemic drug uptake in brain metastasis.

  11. Role of decreased Plasma Tryptophan in memory deficits observed in Type-I diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, S.; Tabassum, S.; Haider, S. [University of Karachi (Pakistan). Dept. of Biochemistry

    2013-01-15

    Objective: To investigate the relationship between plasma tryptophan and the occurrence of memory dysfunctions in male and female type 1 diabetics. Methods: The case-control study was conducted at two urban healthcare facilities in Karachi from January to June 2009, and comprised 100 diabetic subjects of among whom were 50 men and 50 women. The controls were also similar in number and gender. A questionnaire was used to evaluate the memory impairment in the subjects. Plasma tryptophan was determined by high performance liquid chromatography with ultra-violet method. Students t-test was used to analyse tryptophan data. Results: There was considerable memory impairment in the cases (n=40) compared to the controls (n=5). Results also showed a significant (p<0.01) decrease in plasma tryptophan levels in both male and female diabetic patients. Conclusions: Diabetic subjects exhibited occurrence of memory impairment with concomitant decline in plasma tryptophan levels. The findings indicate that decreased brain uptake of tryptophan and lowered brain 5-hydroxytryptamine levels may be responsible for the memory deficits seen in diabetics. (author)

  12. Role of decreased Plasma Tryptophan in memory deficits observed in Type-I diabetes

    International Nuclear Information System (INIS)

    Ahmad, S.; Tabassum, S.; Haider, S.

    2013-01-01

    Objective: To investigate the relationship between plasma tryptophan and the occurrence of memory dysfunctions in male and female type 1 diabetics. Methods: The case-control study was conducted at two urban healthcare facilities in Karachi from January to June 2009, and comprised 100 diabetic subjects of among whom were 50 men and 50 women. The controls were also similar in number and gender. A questionnaire was used to evaluate the memory impairment in the subjects. Plasma tryptophan was determined by high performance liquid chromatography with ultra-violet method. Students t-test was used to analyse tryptophan data. Results: There was considerable memory impairment in the cases (n=40) compared to the controls (n=5). Results also showed a significant (p<0.01) decrease in plasma tryptophan levels in both male and female diabetic patients. Conclusions: Diabetic subjects exhibited occurrence of memory impairment with concomitant decline in plasma tryptophan levels. The findings indicate that decreased brain uptake of tryptophan and lowered brain 5-hydroxytryptamine levels may be responsible for the memory deficits seen in diabetics. (author)

  13. Brain imaging with 123I-IMP-SPECT in migraine between attacks

    International Nuclear Information System (INIS)

    Schlake, H.P.; Boettger, I.G.G.; Grotemeyer, K.H.; Husstedt, I.W.

    1989-01-01

    123 I-IMP-SPECT brain imaging was performed in patients with classic migraine (n = 5) and migraine accompagnee (n = 18) during the headache-free interval. A regional reduction of tracer uptake into brain was observed in all patients with migraine accompagnee, while in patients with classic migraine only one case showed an area of decreased activity. The most marked alteration was found in a patient with persisting neurological symptoms (complicated migraine). In most cases the areas of decreased tracer uptake corresponded to headache localization as well as to topography of neurologic symptoms during migraine attacks. It may be concluded that migraine attacks occur in connection with exacerbations of preexisting changes of cerebral autoregulation due to endogenous or exogenous factors

  14. 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

  15. Functional brain imaging to investigate the higher brain dysfunction induced by diffuse brain injury

    International Nuclear Information System (INIS)

    Nariai, Tadashi; Inaji, Motoki; Ohno, Kikuo; Hiura, Mikio; Ishii, Kenji; Hosoda, Chihiro

    2011-01-01

    Higher brain dysfunction is the major problem of patients who recover from neurotrauma the prevents them from returning to their previous social life. Many such patients do not have focal brain damage detected with morphological imaging. We focused on studying the focal brain dysfunction that can be detected only with functional imaging with positron emission tomography (PET) in relation to the score of various cognition batteries. Patients who complain of higher brain dysfunction without apparent morphological cortical damage were recruited for this study. Thirteen patients with diffuse axonal injury (DAI) or cerebral concussion was included. They underwent a PET study to image glucose metabolism by 18 F-fluorodeoxyglucose (FDG), and central benodiazepine receptor (cBZD-R) (marker of neuronal body) by 11 C-flumazenil, together with cognition measurement by WAIS-R, WMS-R, and WCST etc. PET data were compared with age matched normal controls using statistical parametric mapping (SPM)2. DAI patients had a significant decrease in glucose matabolism and cBZD-R distribution in the cingulated cortex than normal controls. Patients diagnosed with concussion because of shorter consciousness disturbance also had abnormal FDG uptake and cBZD-R distribution. Cognition test scores were variable among patients. Degree of decreased glucose metabolism and cBZD-R distribution in the dominant hemishphere corresponded well to the severity of cognitive disturbance. PET molecular imaging was useful to depict focal cortical dysfunction of neurotrauma patients even when morphological change was not apparent. This method may be promising to clarify the pathophysiology of higher brain dysfunction of patients with diffuse axonal injury or chronic traumatic encephalopathy. (author)

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  17. Altered resting state brain networks in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Martin Göttlich

    Full Text Available Parkinson's disease (PD is a neurodegenerative disorder affecting dopaminergic neurons in the substantia nigra leading to dysfunctional cortico-striato-thalamic-cortical loops. In addition to the characteristic motor symptoms, PD patients often show cognitive impairments, affective changes and other non-motor symptoms, suggesting system-wide effects on brain function. Here, we used functional magnetic resonance imaging and graph-theory based analysis methods to investigate altered whole-brain intrinsic functional connectivity in PD patients (n = 37 compared to healthy controls (n = 20. Global network properties indicated less efficient processing in PD. Analysis of brain network modules pointed to increased connectivity within the sensorimotor network, but decreased interaction of the visual network with other brain modules. We found lower connectivity mainly between the cuneus and the ventral caudate, medial orbitofrontal cortex and the temporal lobe. To identify regions of altered connectivity, we mapped the degree of intrinsic functional connectivity both on ROI- and on voxel-level across the brain. Compared to healthy controls, PD patients showed lower connectedness in the medial and middle orbitofrontal cortex. The degree of connectivity was also decreased in the occipital lobe (cuneus and calcarine, but increased in the superior parietal cortex, posterior cingulate gyrus, supramarginal gyrus and supplementary motor area. Our results on global network and module properties indicated that PD manifests as a disconnection syndrome. This was most apparent in the visual network module. The higher connectedness within the sensorimotor module in PD patients may be related to compensation mechanism in order to overcome the functional deficit of the striato-cortical motor loops or to loss of mutual inhibition between brain networks. Abnormal connectivity in the visual network may be related to adaptation and compensation processes as a consequence

  18. 99mTc-bicisate reliably images CBF in chronic brain diseases but fails to show reflow hyperemia in subacute stroke

    DEFF Research Database (Denmark)

    Lassen, N A; Sperling, B

    1994-01-01

    of 115 cases were collected, and of these 105 were considered technically adequate, comprising 18 normal subjects, 18 senile dementia, eight epilepsy, one brain tumor, eight chronic head trauma, and 52 stroke cases. As expected, bicisate gave better spatial resolution than Xe. Agreement between...... the results of the two methods was noted in 98 cases, but not in the remaining 7, all belonging to the stroke group. These seven all suffered from a subacute stroke (11-23 days after onset), and the disagreement in all cases consisted of bicisate showing low count rate in the area of the infarct and Xe...... a normal or elevated flow (luxury perfusion) as sign of spontaneous thrombolysis with reperfusion; in fact, these seven cases comprised all the reperfusion cases in the series. The results validate bicisate as a tracer of CBF in normal humans and in chronic brain diseases. Only in a subgroup of subacute...

  19. Reduction of the cholesterol sensor SCAP in the brains of mice causes impaired synaptic transmission and altered cognitive function.

    Directory of Open Access Journals (Sweden)

    Ryo Suzuki

    Full Text Available The sterol sensor SCAP is a key regulator of SREBP-2, the major transcription factor controlling cholesterol synthesis. Recently, we showed that there is a global down-regulation of cholesterol synthetic genes, as well as SREBP-2, in the brains of diabetic mice, leading to a reduction of cholesterol synthesis. We now show that in mouse models of type 1 and type 2 diabetes, this is, in part, the result of a decrease of SCAP. Homozygous disruption of the Scap gene in the brains of mice causes perinatal lethality associated with microcephaly and gliosis. Mice with haploinsufficiency of Scap in the brain show a 60% reduction of SCAP protein and ~30% reduction in brain cholesterol synthesis, similar to what is observed in diabetic mice. This results in impaired synaptic transmission, as measured by decreased paired pulse facilitation and long-term potentiation, and is associated with behavioral and cognitive changes. Thus, reduction of SCAP and the consequent suppression of cholesterol synthesis in the brain may play an important role in the increased rates of cognitive decline and Alzheimer disease observed in diabetic states.

  20. Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain.

    Science.gov (United States)

    Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

    2008-01-01

    TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

  1. Oxygen--a limiting factor for brain recovery.

    Science.gov (United States)

    Hadanny, Amir; Efrati, Shai

    2015-09-01

    Effective brain metabolism is highly dependent on a narrow therapeutic window of oxygen. In major insults to the brain (e.g., intracerebral hemorrhage), a slight decrease in oxygen supply, as occurs in a hypobaric environment at high altitude, has devastating effects on the injured brain tissue. Conversely, increasing brain oxygenation, by the use of hyperbaric oxygen therapy, can improve brain metabolism and its dependent regenerative processes.

  2. Oxygen - a limiting factor for brain recovery

    OpenAIRE

    Hadanny, Amir; Efrati, Shai

    2015-01-01

    Effective brain metabolism is highly dependent on a narrow therapeutic window of oxygen. In major insults to the brain (e.g., intracerebral hemorrhage), a slight decrease in oxygen supply, as occurs in a hypobaric environment at high altitude, has devastating effects on the injured brain tissue. Conversely, increasing brain oxygenation, by the use of hyperbaric oxygen therapy, can improve brain metabolism and its dependent regenerative processes.

  3. Inhibition of Brain Swelling after Ischemia-Reperfusion by β-Adrenergic Antagonists: Correlation with Increased K+ and Decreased Ca2+ Concentrations in Extracellular Fluid

    Directory of Open Access Journals (Sweden)

    Dan Song

    2014-01-01

    Full Text Available Infarct size and brain edema following ischemia/reperfusion are reduced by inhibitors of the Na+, K+, 2Cl−, and water cotransporter NKCC1 and by β1-adrenoceptor antagonists. NKCC1 is a secondary active transporter, mainly localized in astrocytes, driven by transmembrane Na+/K+ gradients generated by the Na+,K+-ATPase. The astrocytic Na+,K+-ATPase is stimulated by small increases in extracellular K+ concentration and by the β-adrenergic agonist isoproterenol. Larger K+ increases, as occurring during ischemia, also stimulate NKCC1, creating cell swelling. This study showed no edema after 3 hr medial cerebral artery occlusion but pronounced edema after 8 hr reperfusion. The edema was abolished by inhibitors of specifically β1-adrenergic pathways, indicating failure of K+-mediated, but not β1-adrenoceptor-mediated, stimulation of Na+,K+-ATPase/NKCC1 transport during reoxygenation. Ninety percent reduction of extracellular Ca2+ concentration occurs in ischemia. Ca2+ omission abolished K+ uptake in normoxic cultures of astrocytes after addition of 5 mM KCl. A large decrease in ouabain potency on K+ uptake in cultured astrocytes was also demonstrated in Ca2+-depleted media, and endogenous ouabains are needed for astrocytic K+ uptake. Thus, among the ionic changes induced by ischemia, the decrease in extracellular Ca2+ causes failure of the high-K+-stimulated Na+,K+-ATPase/NKCC1 ion/water uptake, making β1-adrenergic activation the only stimulus and its inhibition effective against edema.

  4. Decreased NAA in gray matter is correlated with decreased availability of acetate in white matter in postmortem multiple sclerosis cortex.

    Science.gov (United States)

    Li, S; Clements, R; Sulak, M; Gregory, R; Freeman, E; McDonough, J

    2013-11-01

    Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system (CNS) which leads to progressive neurological disability. Our previous studies have demonstrated mitochondrial involvement in MS cortical pathology and others have documented decreased levels of the neuronal mitochondrial metabolite N-acetyl aspartate (NAA) in the MS brain. While NAA is synthesized in neurons, it is broken down in oligodendrocytes into aspartate and acetate. The resulting acetate is incorporated into myelin lipids, linking neuronal mitochondrial function to oligodendrocyte-mediated elaboration of myelin lipids in the CNS. In the present study we show that treating human SH-SY5Y neuroblastoma cells with the electron transport chain inhibitor antimycin A decreased levels of NAA as measured by HPLC. To better understand the significance of the relationship between mitochondrial function and levels of NAA and its breakdown product acetate on MS pathology we then quantitated the levels of NAA and acetate in MS and control postmortem tissue blocks. Regardless of lesion status, we observed that levels of NAA were decreased 25 and 32 % in gray matter from parietal and motor cortex in MS, respectively, compared to controls. Acetate levels in adjacent white matter mirrored these decreases as evidenced by the 36 and 45 % reduction in acetate obtained from parietal and motor cortices. These data suggest a novel mechanism whereby mitochondrial dysfunction and reduced NAA levels in neurons may result in compromised myelination by oligodendrocytes due to decreased availability of acetate necessary for the synthesis of myelin lipids.

  5. Age-related brain atrophy and mental deterioration - a study with computed tomography

    International Nuclear Information System (INIS)

    Ito, M.; Hatazawa, J.; Yamaura, H.; Matsuzawa, T.

    1981-01-01

    The relation of brain atrophy measured with computed tomography (CT) to mental deterioration on living people was studied. A newly improved technique for quantitative measurement of brain atrophy was developed. The pixels inside the head slices were divided into three parts; brain skull, and cerebrospinal fluid according to their CT number. The volume of brain, CSF, and cranial cavity were calculated by counting the number of pixels of each tissue. Results from 130 normal brains showed that the CSF volume was constant at about 16 ml through 20-39 years old. After 40 years the mean CSF volume increased drastically and reached 71 ml in the seventies. The volume of the brain was standardized for comparison between different-sized heads (brain volume index: BVI). The mean BVI decreased with statistical significance after 40 years of age. Mental function of these persons were evaluated using Hasegawa's dementia rating scale for the elderly. Progression of brain atrophy accompanied loss of mental activities (p<0.01). (author)

  6. Testosterone supplementation restores vasopressin innervation in the senescent rat brain

    NARCIS (Netherlands)

    Goudsmit, E.; Fliers, E.; Swaab, D. F.

    1988-01-01

    The vasopressin (AVP) innervation in the male rat brain is decreased in senescence. This decrease is particularly pronounced in brain regions where AVP fiber density is dependent on plasma levels of sex steroids. Since plasma testosterone levels decrease progressively with age in the rat, the

  7. Patients with Chronic Visceral Pain Show Sex-Related Alterations in Intrinsic Oscillations of the Resting Brain

    Science.gov (United States)

    Hong, Jui-Yang; Kilpatrick, Lisa A.; Labus, Jennifer; Gupta, Arpana; Jiang, Zhiguo; Ashe-McNalley, Cody; Stains, Jean; Heendeniya, Nuwanthi; Ebrat, Bahar; Smith, Suzanne; Tillisch, Kirsten; Naliboff, Bruce

    2013-01-01

    Abnormal responses of the brain to delivered and expected aversive gut stimuli have been implicated in the pathophysiology of irritable bowel syndrome (IBS), a visceral pain syndrome occurring more commonly in women. Task-free resting-state functional magnetic resonance imaging (fMRI) can provide information about the dynamics of brain activity that may be involved in altered processing and/or modulation of visceral afferent signals. Fractional amplitude of low-frequency fluctuation is a measure of the power spectrum intensity of spontaneous brain oscillations. This approach was used here to identify differences in the resting-state activity of the human brain in IBS subjects compared with healthy controls (HCs) and to identify the role of sex-related differences. We found that both the female HCs and female IBS subjects had a frequency power distribution skewed toward high frequency to a greater extent in the amygdala and hippocampus compared with male subjects. In addition, female IBS subjects had a frequency power distribution skewed toward high frequency in the insula and toward low frequency in the sensorimotor cortex to a greater extent than male IBS subjects. Correlations were observed between resting-state blood oxygen level-dependent signal dynamics and some clinical symptom measures (e.g., abdominal discomfort). These findings provide the first insight into sex-related differences in IBS subjects compared with HCs using resting-state fMRI. PMID:23864686

  8. Hypothalamus-Related Resting Brain Network Underlying Short-Term Acupuncture Treatment in Primary Hypertension

    Directory of Open Access Journals (Sweden)

    Hongyan Chen

    2013-01-01

    Full Text Available The present study attempted to explore modulated hypothalamus-seeded resting brain network underlying the cardiovascular system in primary hypertensive patients after short-term acupuncture treatment. Thirty right-handed patients (14 male were divided randomly into acupuncture and control groups. The acupuncture group received a continuous five-day acupuncture treatment and undertook three resting-state fMRI scans and 24-hour ambulatory blood pressure monitoring (ABPM as well as SF-36 questionnaires before, after, and one month after acupuncture treatment. The control group undertook fMRI scans and 24-hour ABPM. For verum acupuncture, average blood pressure (BP and heart rate (HR decreased after treatment but showed no statistical differences. There were no significant differences in BP and HR between the acupuncture and control groups. Notably, SF-36 indicated that bodily pain (P = 0.005 decreased and vitality (P = 0.036 increased after acupuncture compared to the baseline. The hypothalamus-related brain network showed increased functional connectivity with the medulla, brainstem, cerebellum, limbic system, thalamus, and frontal lobes. In conclusion, short-term acupuncture did not decrease BP significantly but appeared to improve body pain and vitality. Acupuncture may regulate the cardiovascular system through a complicated brain network from the cortical level, the hypothalamus, and the brainstem.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-07-01

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

  10. Aluminium and Gamma Irradiation Induced Oxidative Damage in Brain Tissue of Male Rats - Protective Role of Ferulic Acid

    International Nuclear Information System (INIS)

    Mansour, S.Z.; Hanafi, N.; Noaman, E.

    2011-01-01

    The current study was carried out to investigate the potential role of ferulic acid (FA) against Aluminium chloride (AlCl 3 ), γ- radiation either alone or combination induced oxidative stress in brain tissue of Wistar rats. The period of the experiment was eight weeks. Animals were administrated by aluminium chloride at a dose of 8.5 mg/kg/day and exposed to a single dose (4 Gy) of γ-radiation. FA was administered orally (50 mg/Kg body weight)/day. Histopathological observations and myeloid protein distribution were recorded in brain tissue. Induction of oxidative stress was recorded after all exposures. Brain tissue of AlCl 3 and γ- irradiation treatments either alone or combined revealed many altered changes and myeloid protein distribution. Also a decrease in serotonin concentration was recorded. An increase in Malonaldialdahyde (MDA) and acetylcholinesterase activity and percentage of saturated fatty acids in plasma and brain tissue was recorded. Reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) in blood and brain showed a significant decrease. Treatment of AlCl 3 loaded animals by FA showed simple atrophy as shrunken morphology saw in amyotrophic lateral sclerosis and a decrease in myeloid protein deposition. FA treatment of AlCl 3 loaded or irradiated animals represented a significant increase in serotonin concentration and ameliorated affects on oxidative stress markers, acetylcholinesterase activity and percentage of saturated fatty acids in plasma and brain tissue. In conclusion FA has a role in reducing the oxidative stress of AlCl 3 and γ- irradiation on brain tissue of rats

  11. Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation

    Science.gov (United States)

    Reno, Candace M.; Puente, Erwin C.; Sheng, Zhenyu; Daphna-Iken, Dorit; Bree, Adam J.; Routh, Vanessa H.; Kahn, Barbara B.

    2017-01-01

    GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose. PMID:27797912

  12. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms.

    Science.gov (United States)

    Carhart-Harris, Robin L; Roseman, Leor; Bolstridge, Mark; Demetriou, Lysia; Pannekoek, J Nienke; Wall, Matthew B; Tanner, Mark; Kaelen, Mendel; McGonigle, John; Murphy, Kevin; Leech, Robert; Curran, H Valerie; Nutt, David J

    2017-10-13

    Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other 'psychedelics' yet were related to clinical outcomes. A 'reset' therapeutic mechanism is proposed.

  13. Meta-analysis of diffusion tensor imaging (DTI) studies shows altered fractional anisotropy occurring in distinct brain areas in association with depression

    LENUS (Irish Health Repository)

    Murphy, Melissa L

    2011-09-27

    Abstract Fractional anisotropy anomalies occurring in the white matter tracts in the brains of depressed patients may reflect microstructural changes underlying the pathophysiology of this disorder. We conducted a meta-analysis of fractional anisotropy abnormalities occurring in major depressive disorder using voxel-based diffusion tensor imaging studies. Using the Embase, PubMed and Google Scholar databases, 89 relevant data sets were identified, of which 7 (including 188 patients with major depressive disorder and 221 healthy controls) met our inclusion criteria. Authors were contacted to retrieve any additional data required. Coordinates were extracted from clusters of significant white matter fractional anisotropy differences between patients and controls. Relevant demographic, clinical and methodological variables were extracted from each study or obtained directly from authors. The meta-analysis was carried out using Signed Differential Mapping. Patients with depression showed decreased white matter fractional anisotropy values in the superior longitudinal fasciculus and increased fractional anisotropy values in the fronto-occipital fasciculus compared to controls. Using quartile and jackknife sensitivity analysis, we found that reduced fractional anisotropy in the left superior longitudinal fasciculus was very stable, with increases in the right fronto-occipital fasciculus driven by just one study. In conclusion, our meta-analysis revealed a significant reduction in fractional anisotropy values in the left superior longitudinal fasciculus, which may ultimately play an important role in the pathology of depression.

  14. Decreased lymphocyte dopamine transporter in romantic lovers.

    Science.gov (United States)

    Marazziti, Donatella; Baroni, Stefano; Giannaccini, Gino; Piccinni, Armando; Mucci, Federico; Catena-Dell'Osso, Mario; Rutigliano, Grazia; Massimetti, Gabriele; Dell'Osso, Liliana

    2017-06-01

    The role of dopamine (DA) in romantic love is suggested by different evidence and is supported by the findings of some brain imaging studies. The DA transporter (DAT) is a key structure in regulating the concentration of the neurotransmitter in the synaptic cleft. Given the presence of DAT in blood cells, the present study aimed to explore it in resting lymphocytes of 30 healthy subjects of both sexes in the early stage of romantic love (no longer than 6 months), as compared with 30 subjects involved in a long-lasting relationship. All subjects had no physical or psychiatric illness. The DAT was measured by means of the [3H]-WIN 35,428 binding and the [3H]-DA reuptake to resting lymphocytes membranes. Romantic love was assessed by a specific questionnaire developed by us. The results showed that the subjects in the early phase of romantic love had a global alteration of the lymphocyte DAT involving both a decreased number of proteins (Bmax) and a reduced functionality (Vmax). Taken together, these findings would indicate the presence of increased levels of DA in romantic love that, if paralleled by similar concentrations in the brain, would explain some peculiar features of this human feeling.

  15. Mass Spectrometry Imaging Shows Cocaine and Methylphenidate Have Opposite Effects on Major Lipids in Drosophila Brain.

    Science.gov (United States)

    Philipsen, Mai H; Phan, Nhu T N; Fletcher, John S; Malmberg, Per; Ewing, Andrew G

    2018-03-20

    Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to study the effects of cocaine versus methylphenidate administration on both the localization and abundance of lipids in Drosophila melanogaster brain. A J105 ToF-SIMS with a 40 keV gas cluster primary ion source enabled us to probe molecular ions of biomolecules on the fly with a spatial resolution of ∼3 μm, giving us unique insights into the effect of these drugs on molecular lipids in the nervous system. Significant changes in phospholipid composition were observed in the central brain for both. Principal components image analysis revealed that changes occurred mainly for phosphatidylcholines, phosphatidylethanolamines, and phosphatidylinositols. When the lipid changes caused by cocaine were compared with those induced by methylphenidate, it was shown that these drugs exert opposite effects on the brain lipid structure. We speculate that this might relate to the molecular mechanism of cognition and memory.

  16. Brain core temperature of patients with mild traumatic brain injury as assessed by DWI-thermometry

    Energy Technology Data Exchange (ETDEWEB)

    Tazoe, Jun; Yamada, Kei; Akazawa, Kentaro [Kyoto Prefectural University of Medicine, Department of Radiology, Graduate School of Medical Science, Kyoto City, Kyoto (Japan); Sakai, Koji [Kyoto University, Department of Human Health Science, Graduate School of Medicine, Kyoto (Japan); Mineura, Katsuyoshi [Kyoto Prefectural University of Medicine, Department of Neurosurgery, Graduate School of Medical Science, Kyoto City, Kyoto (Japan)

    2014-10-15

    The aim of this study was to assess the brain core temperature of patients with mild traumatic brain injury (mTBI) using a noninvasive temperature measurement technique based on the diffusion coefficient of the cerebrospinal fluid. This retrospective study used the data collected from April 2008 to June 2011. The patient group comprised 20 patients with a Glasgow Coma Scale score of 14 or 15 who underwent magnetic resonance imaging within 30 days after head trauma. The normal control group comprised 14 subjects who volunteered for a brain checkup (known in Japan as ''brain dock''). We compared lateral ventricular (LV) temperature between patient and control groups. Follow-up studies were performed for four patients. LV temperature measurements were successfully performed for both patients and controls. Mean (±standard deviation) measured LV temperature was 36.9 ± 1.5 C in patients, 38.7 ± 1.8 C in follow-ups, and 37.9 ± 1.2 C in controls, showing a significant difference between patients and controls (P = 0.017). However, no significant difference was evident between patients and follow-ups (P = 0.595) or between follow-ups and controls (P = 0.465). A reduction in brain core temperature was observed in patients with mTBI, possibly due to a global decrease in metabolism. (orig.)

  17. Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

    Directory of Open Access Journals (Sweden)

    Najmeh Kabiri

    2016-09-01

    Full Text Available The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99. Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly higher than the Sham group, although right hemispheres in all of the treated groups illustrated higher brain water content than the left ones. Brain anti-oxidant capacity elevated in the ischemic rats treated with Kombucha and in the Sham group. Brain and plasma malondialdehyde concentrations significantly decreased in both of the ischemic groups injected with Kombucha. The findings suggest that Kombucha tea could be useful for the prevention of cerebral damage.

  18. Brain MRI screening showing evidences of early central nervous system involvement in patients with systemic sclerosis.

    Science.gov (United States)

    Mohammed, Reem Hamdy A; Sabry, Yousriah Y; Nasef, Amr A

    2011-05-01

    Systemic sclerosis is a multisystem autoimmune collagen disease where structural and functional abnormalities of small blood vessels prevail. Transient ischemic attacks, ischemic stroke, and hemorrhage have been reported as primary consequence of vascular central nervous system affection in systemic sclerosis. Magnetic resonance imaging is considered to be the most sensitive diagnostic technique for detecting symptomatic and asymptomatic lesions in the brain in cases of multifocal diseases. The objective of this study is to detect subclinical as well as clinically manifest cerebral vasculopathy in patients with systemic sclerosis using magnetic resonance imaging. As much as 30 female patients with systemic sclerosis aged 27-61 years old, with disease duration of 1-9 years and with no history of other systemic disease or cerebrovascular accidents, were enrolled. Age-matched female control group of 30 clinically normal subjects, underwent brain magnetic resonance examination. Central nervous system (CNS) involvement in the form of white matter hyperintense foci of variable sizes were found in significantly abundant forms in systemic sclerosis patients on magnetic resonance evaluation than in age-related control group, signifying a form of CNS vasculopathy. Such foci showed significant correlation to clinical features of organic CNS lesion including headaches, fainting attacks and organic depression as well as to the severity of peripheral vascular disease with insignificant correlation with disease duration. In conclusion, subclinical as well as clinically manifest CNS ischemic vasculopathy is not uncommon in systemic sclerosis patients and magnetic resonance imaging is considered a sensitive noninvasive screening tool for early detection of CNS involvement in patients with systemic sclerosis.

  19. Soft-food diet induces oxidative stress in the rat brain.

    Science.gov (United States)

    Yoshino, Fumihiko; Yoshida, Ayaka; Hori, Norio; Ono, Yumie; Kimoto, Katsuhiko; Onozuka, Minoru; Lee, Masaichi Chang-il

    2012-02-02

    Decreased dopamine (DA) release in the hippocampus may be caused by dysfunctional mastication, although the mechanisms involved remain unclear. The present study examined the effects of soft- and hard-food diets on oxidative stress in the brain, and the relationship between these effects and hippocampal DA levels. The present study showed that DA release in the hippocampus was decreased in rats fed a soft-food diet. Electron spin resonance studies using the nitroxyl spin probe 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl directly demonstrated a high level of oxidative stress in the rat brain due to soft-food diet feeding. In addition, we confirmed that DA directly react with reactive oxygen species such as hydroxyl radical and superoxide. These observations suggest that soft-food diet feeding enhances oxidative stress, which leads to oxidation and a decrease in the release of DA in the hippocampus of rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis.

    Science.gov (United States)

    Saldana, Sandra M; Lee, Heng-Huan; Lowery, Frank J; Khotskaya, Yekaterina B; Xia, Weiya; Zhang, Chenyu; Chang, Shih-Shin; Chou, Chao-Kai; Steeg, Patricia S; Yu, Dihua; Hung, Mien-Chie

    2013-01-01

    Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.

  1. Decrease in endogenous brain allopregnanolone induces autism spectrum disorder (ASD)-like behavior in mice: A novel animal model of ASD.

    Science.gov (United States)

    Ebihara, Ken; Fujiwara, Hironori; Awale, Suresh; Dibwe, Dya Fita; Araki, Ryota; Yabe, Takeshi; Matsumoto, Kinzo

    2017-09-15

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder with core symptoms of social impairments and restrictive repetitive behaviors. Recent evidence has implicated a dysfunction in the GABAergic system in the pathophysiology of ASD. We investigated the role of endogenous allopregnanolone (ALLO), a neurosteroidal positive allosteric modulator of GABA A receptors, in the regulation of ASD-like behavior in male mice using SKF105111 (SKF), an inhibitor of type I and type II 5α-reductase, a rate-limiting enzyme of ALLO biosynthesis. SKF impaired sociability-related performance, as analyzed by three different tests; i.e., the 3-chamber test and social interaction in the open field and resident-intruder tests, without affecting olfactory function elucidated by the buried food test. SKF also induced repetitive grooming behavior without affecting anxiety-like behavior. SKF had no effect on short-term spatial working memory or long-term fear memory, but enhanced latent learning ability in male mice. SKF-induced ASD-like behavior in male mice was abolished by the systemic administration of ALLO (1mg/kg, i.p.) and methylphenidate (MPH: 2.5mg/kg, i.p.), a dopamine transporter inhibitor. The effects of SKF on brain ALLO contents in male mice were reversed by ALLO, but not MPH. On the other hand, SKF failed to induce ASD-like behavior or a decline in brain ALLO contents in female mice. These results suggest that ALLO regulates episodes of ASD-like behavior by positively modulating the function of GABA A receptors linked to the dopaminergic system. Moreover, a sex-dependently induced decrease in brain ALLO contents may provide an animal model to study the main features of ASD. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Progressive and widespread brain damage in ALS: MRI voxel-based morphometry and diffusion tensor imaging study.

    Science.gov (United States)

    Senda, Joe; Kato, Shigenori; Kaga, Tomotsugu; Ito, Mizuki; Atsuta, Naoki; Nakamura, Tomohiko; Watanabe, Hirohisa; Tanaka, Fumiaki; Naganawa, Shinji; Sobue, Gen

    2011-01-01

    We investigated 17 patients with sporadic amyotrophic lateral sclerosis (ALS) using voxel-based morphometry (VBM) and voxel-based analysis of diffusion tensor images (DTI) at baseline and after a six-month follow-up. Compared with 17 healthy controls, ALS patients at baseline showed only minimal white matter volume decreases in the inferior frontal gyrus but marked decreases in the gray matter of several regions, especially in the bilateral paracentral lobule of the premotor cortex. DTI revealed reduced fractional anisotropy in the bilateral corticospinal tracts, insula, ventrolateral premotor cortex, and parietal cortex. Increased mean diffusivity was noted bilaterally in the motor cortex, ventrolateral premotor cortex, insula, hippocampal formation, and temporal gyrus. At the six-month follow-up, ALS patients showed widespread volume decreases in gray matter, and DTI abnormalities extended mainly into the bilateral frontal lobes, while volume changes in the white matter remained minimal but more distinct. Our combined VBM and DTI techniques revealed extra-corticospinal tract neuronal degeneration mainly in the frontotemporal lobe of ALS patients. In particular, follow-up examinations in these patients showed that whole-brain DTI changes occurred predominantly in the regions of brain atrophy. These objective analyses can be used to assess the disease condition of the ALS brain.

  3. 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.)

  4. Interleukin 6 modulates acetylcholinesterase activity of brain neurons; Effet de l`interleukine 6 sur l`activite de l`acetylcholinesterase des neurones centraux

    Energy Technology Data Exchange (ETDEWEB)

    Clarencon, D.; Multon, E.; Galonnier, M.; Estrade, M.; Fournier, C.; Mathieu, J.; Mestries, J.C.; Testylier, G.; Fatome, M.

    1995-12-31

    Classically, radiation injuries results in a peripheral inflammatory process, and we have previously observed an early systemic interleukin 6 (IL-6) release following whole-body irradiation. Besides, we have demonstrated an early decrease of rat or primate brain acetylcholinesterase (AChE) activity a gamma exposure. The object of the present study is to find possible IL-6 systemic effects on the brain AChE activity. We show that, though intravenous (i.v.) or intra-cerebro-ventricular (ICV) injection of IL-6 can induce a drop in rat brain AChE activity, this cytokine induces only a slight decrease of the AChE release in cultured brain cells. (author). 3 refs.

  5. Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation.

    Science.gov (United States)

    Grimm, Marcus O W; Thiel, Andrea; Lauer, Anna A; Winkler, Jakob; Lehmann, Johannes; Regner, Liesa; Nelke, Christopher; Janitschke, Daniel; Benoist, Céline; Streidenberger, Olga; Stötzel, Hannah; Endres, Kristina; Herr, Christian; Beisswenger, Christoph; Grimm, Heike S; Bals, Robert; Lammert, Frank; Hartmann, Tobias

    2017-12-19

    Alzheimer's disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol) on AD-relevant mechanisms. D₂ and D₃ analogues decreased Aβ-production and increased Aβ-degradation in neuroblastoma cells or vitamin D deficient mouse brains. Effects were mediated by affecting the Aβ-producing enzymes BACE1 and γ-secretase. A reduced secretase activity was accompanied by a decreased BACE1 protein level and nicastrin expression, an essential component of the γ-secretase. Vitamin D and analogues decreased β-secretase activity, not only in mouse brains with mild vitamin D hypovitaminosis, but also in non-deficient mouse brains. Our results further strengthen the link between AD and vitamin D, suggesting that supplementation of vitamin D or vitamin D analogues might have beneficial effects in AD prevention.

  6. Brain networks during free viewing of complex erotic movie: new insights on psychogenic erectile dysfunction.

    Directory of Open Access Journals (Sweden)

    Nicoletta Cera

    Full Text Available Psychogenic erectile dysfunction (ED is defined as a male sexual dysfunction characterized by a persistent or recurrent inability to attain adequate penile erection due predominantly or exclusively to psychological or interpersonal factors. Previous fMRI studies were based on the common occurrence in the male sexual behaviour represented by the sexual arousal and penile erection related to viewing of erotic movies. However, there is no experimental evidence of altered brain networks in psychogenic ED patients (EDp. Some studies showed that fMRI activity collected during non sexual movie viewing can be analyzed in a reliable manner with independent component analysis (ICA and that the resulting brain networks are consistent with previous resting state neuroimaging studies. In the present study, we investigated the modification of the brain networks in EDp compared to healthy controls (HC, using whole-brain fMRI during free viewing of an erotic video clip. Sixteen EDp and nineteen HC were recruited after RigiScan evaluation, psychiatric, and general medical evaluations. The performed ICA showed that visual network (VN, default-mode network (DMN, fronto-parietal network (FPN and salience network (SN were spatially consistent across EDp and HC. However, between-group differences in functional connectivity were observed in the DMN and in the SN. In the DMN, EDp showed decreased connectivity values in the inferior parietal lobes, posterior cingulate cortex and medial prefrontal cortex, whereas in the SN decreased and increased connectivity was observed in the right insula and in the anterior cingulate cortex respectively. The decreased levels of intrinsic functional connectivity principally involved the subsystem of DMN relevant for the self relevant mental simulation that concerns remembering of past experiences, thinking to the future and conceiving the viewpoint of the other's actions. Moreover, the between group differences in the SN nodes

  7. Brain networks during free viewing of complex erotic movie: new insights on psychogenic erectile dysfunction.

    Science.gov (United States)

    Cera, Nicoletta; Di Pierro, Ezio Domenico; Ferretti, Antonio; Tartaro, Armando; Romani, Gian Luca; Perrucci, Mauro Gianni

    2014-01-01

    Psychogenic erectile dysfunction (ED) is defined as a male sexual dysfunction characterized by a persistent or recurrent inability to attain adequate penile erection due predominantly or exclusively to psychological or interpersonal factors. Previous fMRI studies were based on the common occurrence in the male sexual behaviour represented by the sexual arousal and penile erection related to viewing of erotic movies. However, there is no experimental evidence of altered brain networks in psychogenic ED patients (EDp). Some studies showed that fMRI activity collected during non sexual movie viewing can be analyzed in a reliable manner with independent component analysis (ICA) and that the resulting brain networks are consistent with previous resting state neuroimaging studies. In the present study, we investigated the modification of the brain networks in EDp compared to healthy controls (HC), using whole-brain fMRI during free viewing of an erotic video clip. Sixteen EDp and nineteen HC were recruited after RigiScan evaluation, psychiatric, and general medical evaluations. The performed ICA showed that visual network (VN), default-mode network (DMN), fronto-parietal network (FPN) and salience network (SN) were spatially consistent across EDp and HC. However, between-group differences in functional connectivity were observed in the DMN and in the SN. In the DMN, EDp showed decreased connectivity values in the inferior parietal lobes, posterior cingulate cortex and medial prefrontal cortex, whereas in the SN decreased and increased connectivity was observed in the right insula and in the anterior cingulate cortex respectively. The decreased levels of intrinsic functional connectivity principally involved the subsystem of DMN relevant for the self relevant mental simulation that concerns remembering of past experiences, thinking to the future and conceiving the viewpoint of the other's actions. Moreover, the between group differences in the SN nodes suggested a

  8. Patients with severe acquired brain injury show increased arousal in tilt-table training

    DEFF Research Database (Denmark)

    Riberholt, Christian G; Thorlund, Jonas Bloch; Mehlsen, Jesper

    2013-01-01

    Patients with severe acquired brain injury (ABI) are often mobilised using a tilt-table. Complications such as orthostatic intolerance have been reported. The primary objective of this study was to investigate if using a tilt-table was feasible for mobilising patients with severe ABI admitted...... for sub-acute rehabilitation. We also investigated change in arousal, treatment duration before termination due to orthostatic reactions and change in muscle tone....

  9. Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation.

    Science.gov (United States)

    Reno, Candace M; Puente, Erwin C; Sheng, Zhenyu; Daphna-Iken, Dorit; Bree, Adam J; Routh, Vanessa H; Kahn, Barbara B; Fisher, Simon J

    2017-03-01

    GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose. © 2017 by the American Diabetes Association.

  10. Alpha-MSH decreases core and brain temperature during global cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Spulber, S.; Moldovan, Mihai; Oprica, M.

    2005-01-01

    -vessel occlusion forebrain ischemia on core temperature (CT) and brain temperature (BT), respectively. After 10 min cerebral ischemia, BT was lower in alpha-MSH- than in saline-injected animals. After 10 min reperfusion, both CT and BT were lower than the corresponding pre-ischemic levels after injection of alpha...

  11. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    International Nuclear Information System (INIS)

    Schindler, Matthew K.; Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-01-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals

  12. Differentiating the Influences of Aging and Adiposity on Brain Weights, Levels of Serum and Brain Cytokines, Gastrointestinal Hormones, and Amyloid Precursor Protein.

    Science.gov (United States)

    Banks, William A; Abrass, Christine K; Hansen, Kim M

    2016-01-01

    Aging and obesity exert important effects on disease. Differentiating these effects is difficult, however, because weight gain often accompanies aging. Here, we used a nested design of aged, calorically restricted, and refed rats to measure changes in brain and blood levels of cytokines and gastrointestinal hormones, brain amyloid precursor protein levels, and brain and body weights. By comparing groups and using path analysis, we found divergent influences of chronological aging versus body weight, our main findings being (i) changes in whole brain weight and serum macrophage colony-stimulating factor levels correlated better with body weight than with chronological aging, (ii) a decrease in brain cytokines and brain plasminogen activator inhibitor levels correlated better with chronological aging than with body weight, (iii) serum erythropoietin levels were influenced by both body weight and aging, (iv) serum plasminogen activator inhibitor, serum cytokines, and brain tumor necrosis factor were not influenced by aging or body weight, and (v) brain amyloid precursor protein more closely related to body weight and serum levels of gastrointestinal hormones than to brain weight, chronological aging, or cytokines. These findings show that although aging and body weight interact, their influences are distinct not only among various cytokines and hormones but also between the central nervous system and the peripheral tissue compartments. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

  13. Tyrosine kinase inhibitors show different anti-brain metastases efficacy in NSCLC: A direct comparative analysis of icotinib, gefitinib, and erlotinib in a nude mouse model.

    Science.gov (United States)

    Tan, Jianlong; Li, Min; Zhong, Wen; Hu, Chengping; Gu, Qihua; Xie, Yali

    2017-11-17

    Brain metastasis is an increasing problem in non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs), including gefitinib, erlotinib, and icotinib, are reported to be effective in patients with brain metastases. However, direct comparative studies of the pharmacokinetics and efficacy of these three drugs in treating brain metastases are lacking. In the present investigation, we found that gefitinib penetrated the blood-tumor barrier and was distributed to brain metastases more effectively than erlotinib or icotinib in a nude mouse model. The 1-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 9.82±1.03%, 4.83±0.25%, and 2.62±0.21%, respectively. The 2-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 15.11±2.00%, 5.73±1.31%, and 2.69±0.31%, respectively. Gefitinib exhibited the strongest antitumor activity ( p gefitinib vs. erlotinib =0.005; p gefitinib vs. icotinib =0.002). Notably, erlotinib exhibited a better treatment efficacy than icotinib ( p =0.037). Consistently, immunohistochemical data showed that TKIs differentially inhibit the proliferation of metastatical tumor cells. Gefitinib and erlotinib markedly inhibited the proliferation of tumor cells, while there were more ki-67-positive tumor cells in the icotinib group. Additionally, gefitinib inhibited the phosphorylation of EGFR better than the other drugs, whereas pEGFR expression levels in erlotinib groups were lower than levels in the icotinib group ( p gefitinib vs. erlotinib =0.995; p gefitinib vs. icotinib =0.028; p erlotinib vs. icotinib =0.042).Altogether, our findings suggest that gefitinib and erlotinib can inhibit the growth of PC-9-luc brain tumors. Gefitinib demonstrated better antitumor activity and penetration rate in brain metastases than erlotinib or icotinib.

  14. SPM analysis of brain perfusion SPECT and F-18 FDG PET in the Korean autosomal dominant nocturnal frontal lobe epilepsy family

    International Nuclear Information System (INIS)

    Won, Kyoung Sook; Zeon, Seok Kil

    2004-01-01

    This study attempted to investigate the specific pattern of brain perfusion and glucose metabolism in the Korean autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) family. Using Tc-99m ECD brain perfusion SPECT. we assessed brain perfusion in 6 patients at interictal period and 5 patients at ictal period. Interictal F-18 FDG PET was performed on 6 affected family members. The scans were statistically analyzed by using statistical parametric mapping (SPM99). The data of the affected family members were compared to those of the control subjects. Interictal F-18 FDG PET SPM group analysis showed decreased glucose metabolism over the left middle and superior frontal gyri and the left central regions including the anterior parietal lobe. There was a less pronounced decrease in glucose uptake in the right anterior superior frontal gyrus. Interictal brain perfusion SPECT SPM group analysis showed similar pattern of decreased perfusion compared to those of interictal F-18 FDG PET. Ictal brain perfusion SPECT SPM group analysis revealed increased perfusion over the left pre-and postcentral gyri and less pronounced increased perfusion in the right postcentral gyrus. lnterictal F -18 PET and brain perfusion SPECT SPM group analysis suggest that major abnormalities of ADNFLE family are in the left frontal lobe. These findings may be helpful to elucidate the pathophysiological mechanism of this rare disease entity

  15. SPM analysis of brain perfusion SPECT and F-18 FDG PET in the Korean autosomal dominant nocturnal frontal lobe epilepsy family

    Energy Technology Data Exchange (ETDEWEB)

    Won, Kyoung Sook; Zeon, Seok Kil [Keimyung University Dongsan Medical Center, Daegu (Korea, Republic of)

    2004-07-01

    This study attempted to investigate the specific pattern of brain perfusion and glucose metabolism in the Korean autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) family. Using Tc-99m ECD brain perfusion SPECT. we assessed brain perfusion in 6 patients at interictal period and 5 patients at ictal period. Interictal F-18 FDG PET was performed on 6 affected family members. The scans were statistically analyzed by using statistical parametric mapping (SPM99). The data of the affected family members were compared to those of the control subjects. Interictal F-18 FDG PET SPM group analysis showed decreased glucose metabolism over the left middle and superior frontal gyri and the left central regions including the anterior parietal lobe. There was a less pronounced decrease in glucose uptake in the right anterior superior frontal gyrus. Interictal brain perfusion SPECT SPM group analysis showed similar pattern of decreased perfusion compared to those of interictal F-18 FDG PET. Ictal brain perfusion SPECT SPM group analysis revealed increased perfusion over the left pre-and postcentral gyri and less pronounced increased perfusion in the right postcentral gyrus. lnterictal F -18 PET and brain perfusion SPECT SPM group analysis suggest that major abnormalities of ADNFLE family are in the left frontal lobe. These findings may be helpful to elucidate the pathophysiological mechanism of this rare disease entity.

  16. Altered Function and Expression of ABC Transporters at the Blood–Brain Barrier and Increased Brain Distribution of Phenobarbital in Acute Liver Failure Mice

    Directory of Open Access Journals (Sweden)

    Li Liu

    2018-03-01

    Full Text Available This study investigated alterations in the function and expression of P-glycoprotein (P-GP, breast cancer resistance protein (BCRP, and multidrug resistance-associated protein 2 (MRP2 at the blood–brain barrier (BBB of acute liver failure (ALF mice and its clinical significance. ALF mice were developed using intraperitoneal injection of thioacetamide. P-GP, BCRP, and MRP2 functions were determined by measuring the ratios of brain-to-plasma concentration of rhodamine 123, prazosin, and dinitrophenyl-S-glutathione, respectively. The mRNA and proteins expression levels of P-GP, BCRP, and MRP2 were evaluated with quantitative real-time PCR and western blot, respectively. MDCK-MDR1 and HCMEC/D3 cells were used to document the effects of the abnormally altered components in serum of ALF mice on the function and expression of P-GP. The clinical significance of alteration in P-GP function and expression was investigated by determining the distribution of the P-GP substrate phenobarbital (60 mg/kg, intravenous administration in the brain and loss of righting reflex (LORR induced by the drug (100 mg/kg. The results showed that ALF significantly downregulated the function and expression of both P-GP and BCRP, but increased the function and expression of MRP2 in the brain of mice. Cell study showed that increased chenodeoxycholic acid may be a reason behind the downregulated P-GP function and expression. Compared with control mice, ALF mice showed a significantly higher brain concentration of phenobarbital and higher brain-to-plasma concentration ratios. In accordance, ALF mice showed a significantly larger duration of LORR and shorter latency time of LORR by phenobarbital, inferring the enhanced pharmacological effect of phenobarbital on the central nervous system (CNS. In conclusion, the function and expression of P-GP and BCRP decreased, while the function and expression of MRP2 increased in the brain of ALF mice. The attenuated function and expression

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  19. Brain shrinking in chronic alcoholism: CT follow-up study in 65 patients

    Energy Technology Data Exchange (ETDEWEB)

    Schroth, G.; Remmes, U.; Schupmann, A.

    1985-04-01

    CT follow-up studies were done in 65 alcoholics before an inpatient treatment and after a period with confirmed abstinence of 5 weeks duration. The scans were rated 'blind' by linear measurement of well defined distances. An improvement (Significant reduction of brain 'atrophy') was found in 33 patients (50.8%), 5 patients (7,7%) showed a trend towards progression of brain 'atrophy'. The possibility of recovery tends to be significantly greater in younger subjects. These findings and the results of recent MR follow-up studies are consistent with decreased free water during alcohol intoxication and an increase in brain water during alcohol withdrawal.

  20. The Effect of Naloxone on Plasma ET-1 and CGRP Levels in Patients with Traumatic Brain Injury

    International Nuclear Information System (INIS)

    Zhang Chunyin; Guang Ming; Cai Liang; Chen Boxun; Gan Xilun

    2009-01-01

    To investigate the effect of naloxone on the changes of plasma ET-1 and CGRP levels in patients with traumatic brain injury, ninety patients with traumatic brain injury were randomly divided into naloxone treated group and conventionally treated group (both n=45). The plasma levels of ET-1 and CGRP in both groups before and after treatment and in 30 healthy controls were measured by RIA. The results showed that the plasma levels of ET-1 were significantly increased in the patient before treatment and decreased markedly after treatment in both groups. The magnitude of decrease of the plasma ET-1 levels in the naloxone treated group was significantly higher than that in the conventionally treated group (P<0.01). The plasma levels of CGRP were significantly decreased in the patients before treatment and increased markedly after treatment in both groups. The magnitude of increase of the plasma CGRP levels in the naloxone treated group was significantly higher than that in the conventionally treated group (P<0.01). The plasma ET-1 levels in patients with traumatic brain injury was remarkably increased and markedly decreased after treatment with naloxone. The plasma CGRP levels in patients with traumatic brain injury was remarkably decreased and markedly increased after treatment with naloxone. Naloxone has a favorable effect on patient with traumatic brain injury, it may protect the neural cells and improve their living quality. (authors)

  1. Delayed decrease in hemispheric cerebral blood flow during Wada test demonstrated by 99mTc-HMPAO single photon emission computer tomography

    International Nuclear Information System (INIS)

    Ryding, E.; Sjoeholm, H.; Skeidsvoll, H.; Elmqvist, D.

    1989-01-01

    We describe how brain regions with a flow (and metabolism) decrease can be visualized after an injection of short-acting barbiturate in one of the internal carotid arteries during a Wada test. An intravenous administration of 99mTc-HMPAO was used to mark the relative flow distribution. The 99mTc-HMPAO distribution in the brain was recorded three-dimensionally about 1 h later, by means of a single photon emission computer tomograph. We show that the timing of the intravenous 99mTc-HMPAO administration during the Wada test is important for the visualization of the low-flow regions. The administration of the tracer substance should be delayed at least 30 s after the first signs of the barbiturate effect. The rCBF decrease in the barbiturate-injected cerebral hemisphere was associated with a simultaneous decrease in the contralateral, pharmacologically not directly affected, cerebellar hemisphere (crossed cerebellar diaschisis). (author)

  2. Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice.

    Science.gov (United States)

    Wu, Gang; Liu, Xiu-Xiu; Lu, Nan-Nan; Liu, Qi-Bing; Tian, Yun; Ye, Wei-Feng; Jiang, Guo-Jun; Tao, Rong-Rong; Han, Feng; Lu, Ying-Mei

    2017-06-01

    The receptor tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile. In this study, we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. Here, we show that the endothelial cell-specific deletion of ErbB4 induces decreased exploratory behavior in adult mice. However, the water maze task for spatial memory and the memory reconsolidation test reveal no changes; additionally, we observe no impairment in CaMKII phosphorylation in Cdh5Cre;ErbB4 f/f mice, which indicates that the endothelial ErbB4 deficit leads to decreased exploratory activity rather than direct memory deficits. Furthermore, decreased brain metabolism, which was measured using micro-positron emission tomography, is observed in the Cdh5Cre;ErbB4 f/f mice. Consistently, the immunoblot data demonstrate the downregulation of brain Glut1, phospho-ULK1 (Ser555), and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively, our findings suggest that endothelial ErbB4 plays a critical role in regulating brain function, at least in part, through maintaining normal brain energy homeostasis. Targeting ErbB4 or the modulation of endothelial ErbB4 signaling may represent a rational pharmacological approach to treat neurological disorders. © 2017 John Wiley & Sons Ltd.

  3. Patterns of accentuated grey-white differentiation on diffusion-weighted imaging or the apparent diffusion coefficient maps in comatose survivors after global brain injury

    International Nuclear Information System (INIS)

    Kim, E.; Sohn, C.-H.; Chang, K.-H.; Chang, H.-W.; Lee, D.H.

    2011-01-01

    Aim: To determine what disease entities show accentuated grey-white differentiation of the cerebral hemisphere on diffusion-weighted images (DWI) or apparent diffusion coefficient (ADC) maps, and whether there is a correlation between the different patterns and the cause of the brain injury. Methods and materials: The DWI and ADC maps of 19 patients with global brain injury were reviewed and evaluated to investigate whether there was a correlation between the different patterns seen on the DWI and ADC maps and the cause of global brain injury. The ADC values were measured for quantitative analysis. Results: There were three different patterns of ADC decrease: a predominant ADC decrease in only the cerebral cortex (n = 8; pattern I); an ADC decrease in both the cerebral cortex and white matter (WM) and a predominant decrease in the WM (n = 9; pattern II); and a predominant ADC decrease in only the WM (n = 3; pattern III). Conclusion: Pattern I is cerebral cortical injury, suggesting cortical laminar necrosis in hypoxic brain injury. Pattern II is cerebral cortical and WM injury, frequently seen in brain death, while pattern 3 is mainly WM injury, especially found in hypoglycaemic brain injury. It is likely that pattern I is decorticate injury and pattern II is decerebrate injury in hypoxic ischaemic encephalopathy.Patterns I and II are found in severe hypoxic brain injury, and pattern II is frequently shown in brain death, whereas pattern III was found in severe hypoglycaemic injury.

  4. Self-Reported Cognitive Outcomes in Patients With Brain Metastases Before and After Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Ansa Maer [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany); Scherwath, Angela [Department of Medical Psychology, University Medical Centre Hamburg-Eppendorf, Hamburg (Germany); Ernst, Gundula [Department of Medical Psychology, Medical School Hannover, Hannover (Germany); Lanfermann, Heinrich [Institute for Neuroradiology, Medical School Hannover, Hannover (Germany); Bremer, Michael [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany); Steinmann, Diana, E-mail: steinmann.diana@mh-hannover.de [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany)

    2013-11-15

    Purpose: Patients with brain metastases may experience treatment-related cognitive deficits. In this study, we prospectively assessed the self-reported cognitive abilities of patients with brain metastases from any solid primary cancer before and after irradiation of the brain. Methods and Materials: The treatment group (TG) consisted of adult patients (n=50) with brain metastases who received whole or partial irradiation of the brain without having received prior radiation therapy (RT). The control group (CG) consisted of breast cancer patients (n=27) without cranial involvement who were treated with adjuvant RT. Patients were recruited between May 2008 and December 2010. Self-reported cognitive abilities were acquired before RT and 6 weeks, 3 months, and 6 months after irradiation. The information regarding the neurocognitive status was collected by use of the German questionnaires for self-perceived deficits in attention (FEDA) and subjectively experienced everyday memory performance (FEAG). Results: The baseline data showed a high proportion of self-perceived neurocognitive deficits in both groups. A comparison between the TG and the CG regarding the course of self-reported outcomes after RT showed significant between-group differences for the FEDA scales 2 and 3: fatigue and retardation of daily living activities (P=.002) and decrease in motivation (P=.032) with an increase of attention deficits in the TG, but not in the CG. There was a trend towards significance in FEDA scale 1: distractibility and retardation of mental processes (P=.059) between the TG and the CG. The FEAG assessment presented no significant differences. An additional subgroup analysis within the TG was carried out. FEDA scale 3 showed significant differences in the time-related progress between patients with whole-brain RT and those receiving hypofractionated stereotactic RT (P=.025), with less decrease in motivation in the latter group. Conclusion: Self-reported attention declined in

  5. Self-Reported Cognitive Outcomes in Patients With Brain Metastases Before and After Radiation Therapy

    International Nuclear Information System (INIS)

    Cole, Ansa Maer; Scherwath, Angela; Ernst, Gundula; Lanfermann, Heinrich; Bremer, Michael; Steinmann, Diana

    2013-01-01

    Purpose: Patients with brain metastases may experience treatment-related cognitive deficits. In this study, we prospectively assessed the self-reported cognitive abilities of patients with brain metastases from any solid primary cancer before and after irradiation of the brain. Methods and Materials: The treatment group (TG) consisted of adult patients (n=50) with brain metastases who received whole or partial irradiation of the brain without having received prior radiation therapy (RT). The control group (CG) consisted of breast cancer patients (n=27) without cranial involvement who were treated with adjuvant RT. Patients were recruited between May 2008 and December 2010. Self-reported cognitive abilities were acquired before RT and 6 weeks, 3 months, and 6 months after irradiation. The information regarding the neurocognitive status was collected by use of the German questionnaires for self-perceived deficits in attention (FEDA) and subjectively experienced everyday memory performance (FEAG). Results: The baseline data showed a high proportion of self-perceived neurocognitive deficits in both groups. A comparison between the TG and the CG regarding the course of self-reported outcomes after RT showed significant between-group differences for the FEDA scales 2 and 3: fatigue and retardation of daily living activities (P=.002) and decrease in motivation (P=.032) with an increase of attention deficits in the TG, but not in the CG. There was a trend towards significance in FEDA scale 1: distractibility and retardation of mental processes (P=.059) between the TG and the CG. The FEAG assessment presented no significant differences. An additional subgroup analysis within the TG was carried out. FEDA scale 3 showed significant differences in the time-related progress between patients with whole-brain RT and those receiving hypofractionated stereotactic RT (P=.025), with less decrease in motivation in the latter group. Conclusion: Self-reported attention declined in

  6. Brains of verbal memory specialists show anatomical differences in language, memory and visual systems.

    Science.gov (United States)

    Hartzell, James F; Davis, Ben; Melcher, David; Miceli, Gabriele; Jovicich, Jorge; Nath, Tanmay; Singh, Nandini Chatterjee; Hasson, Uri

    2016-05-01

    We studied a group of verbal memory specialists to determine whether intensive oral text memory is associated with structural features of hippocampal and lateral-temporal regions implicated in language processing. Professional Vedic Sanskrit Pandits in India train from childhood for around 10years in an ancient, formalized tradition of oral Sanskrit text memorization and recitation, mastering the exact pronunciation and invariant content of multiple 40,000-100,000 word oral texts. We conducted structural analysis of gray matter density, cortical thickness, local gyrification, and white matter structure, relative to matched controls. We found massive gray matter density and cortical thickness increases in Pandit brains in language, memory and visual systems, including i) bilateral lateral temporal cortices and ii) the anterior cingulate cortex and the hippocampus, regions associated with long and short-term memory. Differences in hippocampal morphometry matched those previously documented for expert spatial navigators and individuals with good verbal working memory. The findings provide unique insight into the brain organization implementing formalized oral knowledge systems. Copyright © 2015. Published by Elsevier Inc.

  7. Dynamics of myelin content decrease in the rat stroke model

    Science.gov (United States)

    Kisel, A.; Khodanovich, M.; Atochin, D.; Mustafina, L.; Yarnykh, V.

    2017-08-01

    The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures.

  8. Decreased nuclear β-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3β conditional transgenic mice

    OpenAIRE

    Lucas, José J.; Hernández, Félix; Gómez-Ramos, Pilar; Morán, María A.; Hen, René; Avila, Jesús

    2001-01-01

    Glycogen synthase kinase-3β (GSK-3β) has been postulated to mediate Alzheimer’s disease tau hyperphosphorylation, β-amyloid-induced neurotoxicity and presenilin-1 mutation pathogenic effects. By using the tet-regulated system we have produced conditional transgenic mice overexpressing GSK-3β in the brain during adulthood while avoiding perinatal lethality due to embryonic transgene expression. These mice show decreased levels of nuclear β-catenin and hyperphosphorylation of tau in hippocampal...

  9. Effects of propranolol and clonidine on brain edema, blood-brain barrier permeability, and endothelial glycocalyx disruption after fluid percussion brain injury in the rat

    DEFF Research Database (Denmark)

    Genét, Gustav Folmer; Bentzer, Peter; Hansen, Morten Bagge

    2018-01-01

    clonidine would decrease brain edema, blood-brain barrier permeability, and glycocalyx disruption at 24 hours after trauma. METHODS: We subjected 53 adult male Sprague-Dawley rats to lateral fluid percussion brain injury and randomized infusion with propranolol (n = 16), propranolol + clonidine (n = 16......), vehicle (n = 16), or sham (n = 5) for 24 hours. Primary outcome was brain water content at 24 hours. Secondary outcomes were blood-brain barrier permeability and plasma levels of syndecan-1 (glycocalyx disruption), cell damage (histone-complexed DNA fragments), epinephrine, norepinephrine, and animal.......555). We found no effect of propranolol and propranolol/clonidine on blood-brain barrier permeability and animal motor scores. Unexpectedly, propranolol and propranolol/clonidine caused an increase in epinephrine and syndecan-1 levels. CONCLUSION: This study does not provide any support for unselective...

  10. On the same wavelength: predictable language enhances speaker-listener brain-to-brain synchrony in posterior superior temporal gyrus.

    Science.gov (United States)

    Dikker, Suzanne; Silbert, Lauren J; Hasson, Uri; Zevin, Jason D

    2014-04-30

    Recent research has shown that the degree to which speakers and listeners exhibit similar brain activity patterns during human linguistic interaction is correlated with communicative success. Here, we used an intersubject correlation approach in fMRI to test the hypothesis that a listener's ability to predict a speaker's utterance increases such neural coupling between speakers and listeners. Nine subjects listened to recordings of a speaker describing visual scenes that varied in the degree to which they permitted specific linguistic predictions. In line with our hypothesis, the temporal profile of listeners' brain activity was significantly more synchronous with the speaker's brain activity for highly predictive contexts in left posterior superior temporal gyrus (pSTG), an area previously associated with predictive auditory language processing. In this region, predictability differentially affected the temporal profiles of brain responses in the speaker and listeners respectively, in turn affecting correlated activity between the two: whereas pSTG activation increased with predictability in the speaker, listeners' pSTG activity instead decreased for more predictable sentences. Listeners additionally showed stronger BOLD responses for predictive images before sentence onset, suggesting that highly predictable contexts lead comprehenders to preactivate predicted words.

  11. Radiotherapy for pediatric brain stem tumors

    International Nuclear Information System (INIS)

    Shcherbenko, O.I.; Parkhomenko, R.A.; Govorina, E.V.; Zelinskaya, N.I.; Ardatova, G.V.; Nechaeva, V.N.

    2000-01-01

    The immediate and short-term results of gamma therapy of brain stem tumors in 24 children were evaluated. All the patients were able to sustain treatment due to adjuvant support with dehydrating and hormonal drugs, and beneficial clinical effect was recorded in 80%. However, magnetic resonance tomography showed no decrease in tumor size. Tumor growth relapsed 3-8 months after radiotherapy. Although total dose ranged 60-72 Gy in 19 patients, there was no clinical evidence of radiation injury [ru

  12. Vitamin D and Its Analogues Decrease Amyloid-β (Aβ Formation and Increase Aβ-Degradation

    Directory of Open Access Journals (Sweden)

    Marcus O. W. Grimm

    2017-12-01

    Full Text Available Alzheimer’s disease (AD is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ, as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol on AD-relevant mechanisms. D2 and D3 analogues decreased Aβ-production and increased Aβ-degradation in neuroblastoma cells or vitamin D deficient mouse brains. Effects were mediated by affecting the Aβ-producing enzymes BACE1 and γ-secretase. A reduced secretase activity was accompanied by a decreased BACE1 protein level and nicastrin expression, an essential component of the γ-secretase. Vitamin D and analogues decreased β-secretase activity, not only in mouse brains with mild vitamin D hypovitaminosis, but also in non-deficient mouse brains. Our results further strengthen the link between AD and vitamin D, suggesting that supplementation of vitamin D or vitamin D analogues might have beneficial effects in AD prevention.

  13. 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.

  14. 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.

  15. Abnormal hemodynamic response to forepaw stimulation in rat brain after cocaine injection

    Science.gov (United States)

    Chen, Wei; Park, Kicheon; Choi, Jeonghun; Pan, Yingtian; Du, Congwu

    2015-03-01

    Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine's effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.

  16. Brain connectivity study of brain tumor patients using MR-PET data: preliminary results

    International Nuclear Information System (INIS)

    Mendes, Ana Carina; Ribeiro, Andre Santos; Oros-Peusquens, Ana Maria; Langen, Karl Josef; Shah, Jon; Ferreira, Hugo Alexandre

    2015-01-01

    Brain activity results from anatomical and functional connections that can be disrupted or altered due to trauma or lesion. This work presents a first approach on the study of whole-brain connectivity of brain tumor patients using the Multimodal Imaging Brain Connectivity (MIBCA) toolbox. Two patients with glioblastoma lesions located in the left hemisphere (one in the motor cortex and the other in the temporal lobe) underwent simultaneous MRI and dynamic PET scans using a 3T MRI scanner with a BrainPET insert. The following data was acquired: T1-w MPRAGE (1x1x1mm 3 ), DTI (dir=30, b=0,800s/mm2, 2x2x2mm 3 ), and dynamic 18F-FET PET. The MIBCA toolbox was used to automatically pre-process MRI-PET data and to derive imaging and connectivity metrics from the multimodal data. Computed metrics included: cortical thickness from T1-w data; mean diffusivity (MD), fractional anisotropy (FA), node degree, clustering coefficient and pairwise ROI fibre tracking (structural connectivity) from DTI data; and standardized uptake value (SUV) from PET data. For all the metrics, the differences between left and right hemispherical structures were obtained, followed by a 25% threshold (except for SUV thresholded at 15%). Data was visualized in a connectogram, and both structural connectivity and metrics were studied in regions surrounding lesions. Preliminary results showed increased SUV values in regions surrounding the tumor for both patients. Patients also showed changes in structural connectivity involving these regions and also other more spatially distant regions such as the putamen and the pallidum, including decreased number of fibers between the subcortical structures themselves and with frontal regions. These findings suggest that the presence of a tumor may alter both local and more distant structural connections. Presently, a larger patient sample is being studied along with the inclusion of a control group to test the consistency of the findings.

  17. Brain connectivity study of brain tumor patients using MR-PET data: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Ana Carina [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon (Portugal); Ribeiro, Andre Santos [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon (Portugal); Centre for Neuropsychopharmacology, Division of Brain Sciences, Department of Medicine, Imperial College London, London (United Kingdom); Oros-Peusquens, Ana Maria; Langen, Karl Josef; Shah, Jon [Institute of Neuroscience and Medicine - 4, Forschungszentrum Juelich (Germany); Ferreira, Hugo Alexandre [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon (Portugal)

    2015-05-18

    Brain activity results from anatomical and functional connections that can be disrupted or altered due to trauma or lesion. This work presents a first approach on the study of whole-brain connectivity of brain tumor patients using the Multimodal Imaging Brain Connectivity (MIBCA) toolbox. Two patients with glioblastoma lesions located in the left hemisphere (one in the motor cortex and the other in the temporal lobe) underwent simultaneous MRI and dynamic PET scans using a 3T MRI scanner with a BrainPET insert. The following data was acquired: T1-w MPRAGE (1x1x1mm{sup 3}), DTI (dir=30, b=0,800s/mm2, 2x2x2mm{sup 3}), and dynamic 18F-FET PET. The MIBCA toolbox was used to automatically pre-process MRI-PET data and to derive imaging and connectivity metrics from the multimodal data. Computed metrics included: cortical thickness from T1-w data; mean diffusivity (MD), fractional anisotropy (FA), node degree, clustering coefficient and pairwise ROI fibre tracking (structural connectivity) from DTI data; and standardized uptake value (SUV) from PET data. For all the metrics, the differences between left and right hemispherical structures were obtained, followed by a 25% threshold (except for SUV thresholded at 15%). Data was visualized in a connectogram, and both structural connectivity and metrics were studied in regions surrounding lesions. Preliminary results showed increased SUV values in regions surrounding the tumor for both patients. Patients also showed changes in structural connectivity involving these regions and also other more spatially distant regions such as the putamen and the pallidum, including decreased number of fibers between the subcortical structures themselves and with frontal regions. These findings suggest that the presence of a tumor may alter both local and more distant structural connections. Presently, a larger patient sample is being studied along with the inclusion of a control group to test the consistency of the findings.

  18. Pharmacologic resuscitation for hemorrhagic shock combined with traumatic brain injury

    DEFF Research Database (Denmark)

    Jin, Guang; Duggan, Michael; Imam, Ayesha

    2012-01-01

    [Hex]) after traumatic brain injury (TBI) decreases brain swelling, without affecting size of the lesion. This study was performed to determine whether addition of VPA to Hex would decrease the lesion size in a clinically relevant large animal model of TBI + HS....

  19. Decreased expression of thyroid receptor-associated protein 220 in temporal lobe tissue of patients with refractory epilepsy

    International Nuclear Information System (INIS)

    Li Jinmei; Wang Xuefeng; Xi Zhiqin; Gong Yun; Liu Fengying; Sun Jijun; Wu Yuan; Luan Guoming; Wang Yuping; Li Yunlin; Zhang Jianguo; Lu Yong; Li Hongwei

    2006-01-01

    Purpose: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. Methods: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. Results: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in the temporal cortex of the patients with epilepsy. Conclusions: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures

  20. Reconstructing the ups and downs of primate brain evolution: implications for adaptive hypotheses and Homo floresiensis

    Directory of Open Access Journals (Sweden)

    Barton Robert A

    2010-01-01

    Full Text Available Abstract Background Brain size is a key adaptive trait. It is often assumed that increasing brain size was a general evolutionary trend in primates, yet recent fossil discoveries have documented brain size decreases in some lineages, raising the question of how general a trend there was for brains to increase in mass over evolutionary time. We present the first systematic phylogenetic analysis designed to answer this question. Results We performed ancestral state reconstructions of three traits (absolute brain mass, absolute body mass, relative brain mass using 37 extant and 23 extinct primate species and three approaches to ancestral state reconstruction: parsimony, maximum likelihood and Bayesian Markov-chain Monte Carlo. Both absolute and relative brain mass generally increased over evolutionary time, but body mass did not. Nevertheless both absolute and relative brain mass decreased along several branches. Applying these results to the contentious case of Homo floresiensis, we find a number of scenarios under which the proposed evolution of Homo floresiensis' small brain appears to be consistent with patterns observed along other lineages, dependent on body mass and phylogenetic position. Conclusions Our results confirm that brain expansion began early in primate evolution and show that increases occurred in all major clades. Only in terms of an increase in absolute mass does the human lineage appear particularly striking, with both the rate of proportional change in mass and relative brain size having episodes of greater expansion elsewhere on the primate phylogeny. However, decreases in brain mass also occurred along branches in all major clades, and we conclude that, while selection has acted to enlarge primate brains, in some lineages this trend has been reversed. Further analyses of the phylogenetic position of Homo floresiensis and better body mass estimates are required to confirm the plausibility of the evolution of its small brain

  1. Cocaine users with comorbid Cluster B personality disorders show dysfunctional brain activation and connectivity in the emotional regulation networks during negative emotion maintenance and reappraisal.

    Science.gov (United States)

    Albein-Urios, Natalia; Verdejo-Román, Juan; Soriano-Mas, Carles; Asensio, Samuel; Martínez-González, José Miguel; Verdejo-García, Antonio

    2013-12-01

    Cocaine dependence often co-occurs with Cluster B personality disorders. Since both disorders are characterized by emotion regulation deficits, we predicted that cocaine comorbid patients would exhibit dysfunctional patterns of brain activation and connectivity during reappraisal of negative emotions. We recruited 18 cocaine users with comorbid Cluster B personality disorders, 17 cocaine users without comorbidities and 21 controls to be scanned using functional magnetic resonance imaging (fMRI) during performance on a reappraisal task in which they had to maintain or suppress the emotions induced by negative affective stimuli. We followed region of interest (ROI) and whole-brain approaches to investigate brain activations and connectivity associated with negative emotion experience and reappraisal. Results showed that cocaine users with comorbid personality disorders had reduced activation of the subgenual anterior cingulate cortex during negative emotion maintenance and increased activation of the lateral orbitofrontal cortex and the amygdala during reappraisal. Amygdala activation correlated with impulsivity and antisocial beliefs in the comorbid group. Connectivity analyses showed that in the cocaine comorbid group the subgenual cingulate was less efficiently connected with the amygdala and the fusiform gyri and more efficiently connected with the anterior insula during maintenance, whereas during reappraisal the left orbitofrontal cortex was more efficiently connected with the amygdala and the right orbitofrontal cortex was less efficiently connected with the dorsal striatum. We conclude that cocaine users with comorbid Cluster B personality disorders have distinctive patterns of brain activation and connectivity during maintenance and reappraisal of negative emotions, which correlate with impulsivity and dysfunctional beliefs. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  2. Brain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation.

    Science.gov (United States)

    Pardo, Beatriz; Rodrigues, Tiago B; Contreras, Laura; Garzón, Miguel; Llorente-Folch, Irene; Kobayashi, Keiko; Saheki, Takeyori; Cerdan, Sebastian; Satrústegui, Jorgina

    2011-01-01

    The glutamate-glutamine cycle faces a drain of glutamate by oxidation, which is balanced by the anaplerotic synthesis of glutamate and glutamine in astrocytes. De novo synthesis of glutamate by astrocytes requires an amino group whose origin is unknown. The deficiency in Aralar/AGC1, the main mitochondrial carrier for aspartate-glutamate expressed in brain, results in a drastic fall in brain glutamine production but a modest decrease in brain glutamate levels, which is not due to decreases in neuronal or synaptosomal glutamate content. In vivo (13)C nuclear magnetic resonance labeling with (13)C(2)acetate or (1-(13)C) glucose showed that the drop in brain glutamine is due to a failure in glial glutamate synthesis. Aralar deficiency induces a decrease in aspartate content, an increase in lactate production, and lactate-to-pyruvate ratio in cultured neurons but not in cultured astrocytes, indicating that Aralar is only functional in neurons. We find that aspartate, but not other amino acids, increases glutamate synthesis in both control and aralar-deficient astrocytes, mainly by serving as amino donor. These findings suggest the existence of a neuron-to-astrocyte aspartate transcellular pathway required for astrocyte glutamate synthesis and subsequent glutamine formation. This pathway may provide a mechanism to transfer neuronal-born redox equivalents to mitochondria in astrocytes.

  3. Technetium-99m-ECD SPECT in antiphospholipid antibody syndrome: a drastic improvement in brain perfusion by antiplatelet therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tokumaru, Sunao; Yoshikai, Tomonori; Uchino, Akira; Kudo, Sho [Dept. of Radiology, Saga Medical School (Japan); Matsui, Makoto; Kuroda, Yasuo [Dept. of Neurology, Saga Medical School (Japan)

    2001-12-01

    We present a case of antiphospholipid antibody syndrome (APS) with repeated transient ischemic attacks (TIAs). Magnetic resonance imaging showed multiple cerebral infarcts and ischemic changes in the cerebral white matter. Cerebral angiographies showed no abnormalities. Technetium-99m-ethyl cysteinate dimer (Tc-99m-ECD) brain SPECT showed multiple decreased perfusion areas, which were more extensive than the lesions demonstrated on MRI. After treatment with an antiplatelet agent, the patient subsequently recovered from the TIAs. Although no interval changes were observed by MRI after therapy, follow-up Tc-99m-ECD SPECT revealed a marked improvement in brain perfusion. This is the first imaging report of remarkable post-therapy improvement in brain perfusion in APS cases. (orig.)

  4. Technetium-99m-ECD SPECT in antiphospholipid antibody syndrome: a drastic improvement in brain perfusion by antiplatelet therapy

    International Nuclear Information System (INIS)

    Tokumaru, Sunao; Yoshikai, Tomonori; Uchino, Akira; Kudo, Sho; Matsui, Makoto; Kuroda, Yasuo

    2001-01-01

    We present a case of antiphospholipid antibody syndrome (APS) with repeated transient ischemic attacks (TIAs). Magnetic resonance imaging showed multiple cerebral infarcts and ischemic changes in the cerebral white matter. Cerebral angiographies showed no abnormalities. Technetium-99m-ethyl cysteinate dimer (Tc-99m-ECD) brain SPECT showed multiple decreased perfusion areas, which were more extensive than the lesions demonstrated on MRI. After treatment with an antiplatelet agent, the patient subsequently recovered from the TIAs. Although no interval changes were observed by MRI after therapy, follow-up Tc-99m-ECD SPECT revealed a marked improvement in brain perfusion. This is the first imaging report of remarkable post-therapy improvement in brain perfusion in APS cases. (orig.)

  5. Smaller Brains and Optic Lobes in Reproductive Workers of the Ant Harpegnathos

    Science.gov (United States)

    Gronenberg, Wulfila; Liebig, Jürgen

    Most animals show long-term modifications of their behavior which often reflect an adaptation to seasonal variations (e.g., hibernation) or result from changes in the animal's internal state (e.g., estrous cycle or sexual maturity). Such modifications may substantially affect the nervous system [1, 2]. A particularly striking behavioral change can occur in workers of the ant Harpegnathos. A few young workers in the colony may become reproductives and are thus confined to their dark nest chambers, whereas most workers spend their lives as foragers, employing acute vision when hunting prey. This behavioral difference coincides with a marked decrease in brain volume and with an even stronger reduction in the large visual brain centers. Instead of maintaining superfluous brain functions, these ants reduce brain matter which is expensive to support.

  6. Air pollutant sulfur dioxide-induced alterations on the levels of lipids, lipid peroxidation and lipase activity in various regions of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Haider, S S; Hasan, M; Khan, N H

    1982-07-01

    The exposure of rats to SO/sub 2/ (10 p.p.m.) for one hour daily for 30 days caused depletion of total lipids in all brain areas. The contents of phospholipid were elevated in cerebellum and brain stem, but were depleted in cerebral hemisphere. Cholesterol levels showed an increase in various brain regions. On the other hand, gangliosides were increased in cerebellum and brain stem, but were decreased in cerebral hemisphere. Interestingly, cholesterol/phospholipid ratio was increased in different regions of the brain. Lipase activity was elevated in cerebral hemisphere. Lipid peroxidation showed marked increment in whole brain and in all the brain areas studied. The results suggest that SO/sub 2/-exposure induces degradation of lipids. Interestingly, the lipid contents are affected differentially in the various parts of the brain.

  7. Cerebral blood flow of the non-affected brain in patients with malignant brain tumors as studied by SPECT

    International Nuclear Information System (INIS)

    Araki, Yuzo; Imao, Yukinori; Hirata, Toshifumi; Ando, Takashi; Sakai, Noboru; Yamada, Hiroshi

    1990-01-01

    In 40 patients (age range, 20-69 years) receiving radiation and chemotherapy for brain tumors, the mean cerebral blood flow (mCBF) in the non-affected area has been examined by single photon emission CT (SPECT) with Xe-133. Forty volunteers (age range, 25-82 years) served as controls. Although mCBF during external irradiation was transiently increased, it was significantly decreased at 3 months after beginning of external irradiation compared with that in the control group. Factors responsible for the decrease in mCBF were radiation doses, lesion volume, the degree of cerebral atrophy, and age; this was more pronounced when chemotherapy such as ACNU was combined with radiation. A decreased mCBF was independent of intraoperative radiation combined with external radiation and either local or whole brain irradiation. SPECT with Xe-133 was useful in determining minute changes in cerebral blood flow that precedes parenchymal brain damage. (N.K.)

  8. Effect of brain-derived neurotrophic factor on the formation of psycho-vegetative syndrome with brain injury

    Directory of Open Access Journals (Sweden)

    Selyanina N.V.

    2016-09-01

    Full Text Available Aim: to determine the role of brain-derived neurotrophic factor in the formation and forecasting of psycho-vegetative syndrome in patients with cerebral mild to moderate injury. Material and Methods. There have been 150 patients with contusion of the brain, examined. Indicators of neurological, psycho-vegetative status, quantitative content of brain-derived neurotrophic factor (BDNF and nerve growth factor (NGF in the serum were studied. Results. At patients with brain contusion neurological, psycho-vegetative disturbances and decrease neurotrophic factors are determined. It was found to depend of the content of BDNF and psycho-vegetative indicators. Conclusion. The level of brain-derived neurotrophic factor serum (less than 300 pg/ml is a predictor of psycho-vegetative syndrome in the long term of the brain injury.

  9. College Binge Drinking Associated with Decreased Frontal Activation to Negative Emotional Distractors during Inhibitory Control

    Directory of Open Access Journals (Sweden)

    Julia E. Cohen-Gilbert

    2017-09-01

    Full Text Available The transition to college is associated with an increase in heavy episodic alcohol use, or binge drinking, during a time when the prefrontal cortex and prefrontal-limbic circuitry continue to mature. Traits associated with this immaturity, including impulsivity in emotional contexts, may contribute to risky and heavy episodic alcohol consumption. The current study used blood oxygen level dependent (BOLD multiband functional magnetic resonance imaging (fMRI to assess brain activation during a task that required participants to ignore background images with positive, negative, or neutral emotional valence while performing an inhibitory control task (Go-NoGo. Subjects were 23 college freshmen (seven male, 18–20 years who engaged in a range of drinking behavior (past 3 months’ binge episodes range = 0–19, mean = 4.6, total drinks consumed range = 0–104, mean = 32.0. Brain activation on inhibitory trials (NoGo was contrasted between negative and neutral conditions and between positive and neutral conditions using non-parametric testing (5000 permutations and cluster-based thresholding (z = 2.3, p ≤ 0.05 corrected. Results showed that a higher recent incidence of binge drinking was significantly associated with decreased activation of dorsolateral prefrontal cortex (DLPFC, dorsomedial prefrontal cortex (DMPFC, and anterior cingulate cortex (ACC, brain regions strongly implicated in executive functioning, during negative relative to neutral inhibitory trials. No significant associations between binge drinking and brain activation were observed for positive relative to neutral images. While task performance was not significantly associated with binge drinking in this sample, subjects with heavier recent binge drinking showed decreased recruitment of executive control regions under negative versus neutral distractor conditions. These findings suggest that in young adults with heavier recent binge drinking, processing of negative emotional

  10. Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognition in urban children.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Cross, Janet V; Engle, Randall; Aragón-Flores, Mariana; Gómez-Garza, Gilberto; Jewells, Valerie; Medina-Cortina, Humberto; Solorio, Edelmira; Chao, Chih-Kai; Zhu, Hongtu; Mukherjee, Partha S; Ferreira-Azevedo, Lara; Torres-Jardón, Ricardo; D'Angiulli, Amedeo

    2013-01-01

    Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA) children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-β diffuse plaques (compared to 0% in low pollution control children). We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1) and/or inflammatory mediators in MCMA children. Thirty gram of dark cocoa with 680 mg of total flavonols were given daily for 10.11 ± 3.4 days (range 9-24 days) to 18 children (10.55 years, SD = 1.45; 11F/7M). Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p = 0.0002). Fifteen children (83%) showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter (PM) and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer's and Parkinson's diseases.

  11. Irradiation of rat brain reduces P-glycoprotein expression and function

    NARCIS (Netherlands)

    Bart, J.; Nagengast, W. B.; Coppes, R. P.; Wegman, T. D.; van der Graaf, W. T. A.; Groen, H. J. M.; Vaalburg, W.; de Vries, E. G. E.; Hendrikse, N. H.

    2007-01-01

    The blood - brain barrier ( BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P- glycoprotein ( P- gp), expressed on brain capillary endothelial cells, is part of the BBB. P- gp expression on capillary endothelium decreases 5 days after brain

  12. Regional amino acid transport into brain during diabetes: Effect of plasma amino acids

    International Nuclear Information System (INIS)

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

    1987-01-01

    Transport of phenylalanine and lysine into the brain was measured in 4-wk streptozotocin-diabetic rats to assess the effect on the neutral and basic amino acid transport systems at the blood-brain barrier. Amino acid concentrations in plasma and brain were also measured. Regional permeability-times-surface area (PS) products and influx were determined using a continuous infusion method and quantitative autoradiography. The PS of phenylalanine was decreased by an average of 40% throughout the entire brain. Influx was depressed by 35%. The PS of lysine was increased by an average of 44%, but the influx was decreased by 27%. Several plasma neutral amino acids (branched chain) were increased, whereas all basic amino acids were decreased. Brain tryptophan, phenylalanine, tyrosine, methionine, and lysine contents were markedly decreased. The transport changes were almost entirely accounted for by the alterations in the concentrations of the plasma amino acids that compete for the neutral and basic amino acid carriers. The reduced influx could be responsible for the low brain content of some essential amino acids, with possibly deleterious consequences for brain functions

  13. Hydrolysis of cytectrene marked by the technetium 99m by acetylcholinesterase in the rat brain and confirmation of fixing the cytectrene on brain receptors

    International Nuclear Information System (INIS)

    Mejri, N.; Barhoumi, M.C.; Mekni, A.; Coulais, Y.; Amri, M.; Masmoudi, O.; Saidi, M

    2008-01-01

    Alzheimer's disease is a degenerative neurological disorder that causes progressive and irreversible loss of mental functions. It is the most common form of dementia and is characterized by a decrease in serotonergic neurons that carry the 5HT1A receptors. We showed that the use of cytectrene for the quantitative measurement of the activity of the Acetylcholinesterase in the brain depends on the rate of hydrolysis and the enzymatic specificity. The results showed that the cytectrene can be used as a substrate for a precise and quantitative determination of the activity of this enzyme. We have made hippocampal and cortical neuron cultures in the brain from young rats. After the differentiation of these neurons, some cell cultures are incubated with 8 OH DPAT, a receptor 5HT1A agonist of the serotonin, which are located on the surface of neurons. The neurons are then incubated with a molecule marked with radioactive technetium 99m Tc. These neurons are crushed and radioactivity is read. The results show that for growing neurons in the hippocampus, we have levels of radioactivity cells treated with agonist, below the level of radioactivity of cells treated with the radioactive molecules. The cortical neurons show the same level of radioactivity in the cells treated with agonist for cells treated only with the molecule marked. Our results show a decrease of fixing the molecule marked on 5HT1A receptor neurons in the hippocampus compared to neurons in the cortex. This work will enable us to prove the decrease of neurons in neuronal diseases and to make the diagnosis of these diseases. (author)

  14. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    2010-07-01

    Full Text Available Dopamine (phasic release is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function was measured with PET and (18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg. The Cocaine-cues video increased craving to the same extent with placebo (68% and with methylphenidate (64%. In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005 in left limbic regions (insula, orbitofrontal, accumbens and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005, amygdala, striatum and middle insula (p<0.05. This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes, which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

  15. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers

    International Nuclear Information System (INIS)

    Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Telang, F.; Fowler, J.S.; Pradhan, K.; Jayne, M.; Logan, J.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2010-01-01

    Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 18 FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

  16. The development of brain network architecture.

    Science.gov (United States)

    Wierenga, Lara M; van den Heuvel, Martijn P; van Dijk, Sarai; Rijks, Yvonne; de Reus, Marcel A; Durston, Sarah

    2016-02-01

    Brain connectivity shows protracted development throughout childhood and adolescence, and, as such, the topology of brain networks changes during this period. The complexity of these changes with development is reflected by regional differences in maturation. This study explored age-related changes in network topology and regional developmental patterns during childhood and adolescence. We acquired two sets of Diffusion Weighted Imaging-scans and anatomical T1-weighted scans. The first dataset included 85 typically developing individuals (53 males; 32 females), aged between 7 and 23 years and was acquired on a Philips Achieva 1.5 Tesla scanner. A second dataset (N = 38) was acquired on a different (but identical) 1.5 T scanner and was used for independent replication of our results. We reconstructed whole brain networks using tractography. We operationalized fiber tract development as changes in mean diffusivity and radial diffusivity with age. Most fibers showed maturational changes in mean and radial diffusivity values throughout childhood and adolescence, likely reflecting increasing white matter integrity. The largest age-related changes were observed in association fibers within and between the frontal and parietal lobes. Furthermore, there was a simultaneous age-related decrease in average path length (P maturational model where connections between unimodal regions strengthen in childhood, followed by connections from these unimodal regions to association regions, while adolescence is characterized by the strengthening of connections between association regions within the frontal and parietal cortex. Hum Brain Mapp 37:717-729, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  17. 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.

  18. Serial changes in metabolism and histology in the cold-injury trauma rat brain model. Proton magnetic resonance imaging and spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Kamada, Kyousuke; Houkin, Kiyohiro; Hida, Kazutoshi; Iwasaki, Yoshinobu; Abe, Hiroshi [Hokkaido Univ., Sapporo (Japan). School of Medicine

    1995-01-01

    The serial changes in metabolism and histology during the first 24 hours in the cold-injury trauma rat brain model were investigated by proton magnetic resonance (MR) imaging and high-resolution proton MR spectroscopy. Edema developed extensively via the corpus callosum in the ipsi- and contralateral hemispheres during observation as shown by gradually increased signal intensity on proton MR images. Proton MR spectroscopy showed increased levels of acetate (Ace), lactate (Lac), and glutamine (Glmi) 1 hour after lesion formation. The elevated Glmi level slightly decreased, the level of alanine (Ala) increased substantially, and that of N-acetyl-aspartate (NAA) decreased markedly after 24 hours. Increased Lac, Ace, and Ala might reflect anaerobic glycolysis associated with mitochondrial dysfunction, while decreased Glmi and NAA reveal brain tissue breakdown. The relationship between brain edema and tissue viability can be analyzed in detail using this simple traumatic model and MR techniques which will be useful in the development of therapeutic agents for brain injury. (author).

  19. Localized 31P magnetic resonance spectroscopy of large pediatric brain tumors

    International Nuclear Information System (INIS)

    Sutton, L.N.; Lenkinski, R.E.; Cohen, B.H.; Packer, R.J.; Zimmerman, R.A.

    1990-01-01

    Fourteen children aged 1 week to 16 years, with a variety of large or superficial brain tumors, underwent localized in vivo 31 P magnetic resonance spectroscopy of their tumor. Quantitative spectral analysis was performed by measuring the area under individual peaks using a computer algorithm. In eight patients with histologically benign tumors the spectra were considered to be qualitatively indistinguishable from normal brain. The phosphocreatine/inorganic phosphate ratio (PCr/Pi) averaged 2.0. Five patients had histologically malignant tumors; qualitatively, four of these were considered to have abnormal spectra, showing a decrease in the PCr peak. The PCr/Pi ratio for this group averaged 0.85, which was significantly lower than that seen in the benign tumor group (p less than 0.05). No difference between the two groups was seen in adenosine triphosphate or phosphomonoesters. It is concluded that a specific metabolic fingerprint for childhood brain tumors may not exist, but that some malignant tumors show a pattern suggestive of ischemia

  20. Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration.

    Science.gov (United States)

    Pollard, Amelia Kate; Craig, Emma Louise; Chakrabarti, Lisa

    2016-01-01

    Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70-71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions.

  1. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Brassard, Patrice; Adser, Helle

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) has an important role in regulating maintenance, growth and survival of neurons. However, the main source of circulating BDNF in response to exercise is unknown. To identify whether the brain is a source of BDNF during exercise, eight volunteers rowed for 4...... h while simultaneous blood samples were obtained from the radial artery and the internal jugular vein. To further identify putative cerebral region(s) responsible for BDNF release, mouse brains were dissected and analysed for BDNF mRNA expression following treadmill exercise. In humans, a BDNF...... release from the brain was observed at rest (P BDNF, while that contribution decreased following 1 h of recovery. In mice, exercise induced a three...

  2. Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

    Science.gov (United States)

    Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa-Wołosiuk, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

    2017-09-01

    Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Decreased plasma concentrations of brain-derived neurotrophic factor (BDNF) in patients with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Podfigurna-Stopa, Agnieszka; Casarosa, Elena; Luisi, Michele; Czyzyk, Adam; Meczekalski, Blazej; Genazzani, Andrea Riccardo

    2013-09-01

    Functional hypothalamic amenorrhea (FHA) is a non organic, secondary amenorrhea related to gonadotropin-releasing hormone pulsatile secretion impairment. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays an important role in the growth, development, maintenance and function of several neuronal systems. The aim of the study was the evaluation of plasma BDNF concentrations in patients with the diagnosis of FHA. We studied 85 subjects diagnosed with FHA who were compared with 10 healthy, eumenorrheic controls with normal body mass index. Plasma BDNF and serum luteinizing hormone, follicle-stimulating hormone and estradiol (E2) concentrations were measured by immunoenzymatic method (enzyme-linked immunosorbent assay). Significantly lower concentration of plasma BDNF was found in FHA patients (196.31 ± 35.26 pg/ml) in comparison to healthy controls (407.20 ± 25.71 pg/ml; p < 0.0001). In the control group, there was a strong positive correlation between plasma BDNF and serum E2 concentrations (r = 0.92, p = 0.0001) but in FHA group it was not found. Role of BDNF in FHA is not yet fully understood. There could be found studies concerning plasma BDNF concentrations in humans and animals in the literature. However, our study is one of the first projects which describes decreased plasma BDNF concentration in patients with diagnosed FHA. Therefore, further studies on BDNF in FHA should clarify the role of this peptide.

  4. Characteristics of Brain Perfusion in Patients of Parkinson's Disease

    International Nuclear Information System (INIS)

    Jeong, Young Jin; Park, Min Jung; Kim, Jae Woo; Kang, Young Kang

    2008-01-01

    It was well known that cerebral blood perfusion is normal or diffusely decreased in the majority of patients with Parkinson's disease (PD). Actually we interpreted brain perfusion SPECT images of PD patients in the clinical situation, we observed various cerebral perfusion patterns in patients with PD. So we performed brain perfusion SPECT to know the brain perfusion patterns of PD patients and the difference of perfusion patterns according to the sex and the age. Also we classified PD patients into small groups based on the brain perfusion pattern. Two hundred nineteen patients (M: 70, F: 149, mean age: 62.9±6.9 y/o) who were diagnosed as PD without dementia clinically and 55 patients (M: 15, F: 40, mean age: 61.4±9.2 y/o) as normal controls who had no past illness history were performed 99m Tc-HMPAO brain perfusion SPECT and neuropsychological test. At first, we compared all patients with PD and normal controls. Brain perfusion in left inferior frontal gyrus, left insula, left transverse temporal gyrus, left inferior parietal lobule, left superior parietal lobule, right precuneus, right caudate tail were lower in patients with PD than normal controls. Secondly, we compared male and female patients with PD and normal controls, respectively. Brain perfusion SPECT showed more decreased cerebral perfusion in left hemisphere than right side in both male and female patients compared to normal controls. And there was larger hypoperfusion area in female patients compared with male. Thirdly, we classified patients with PD and normal controls into 4 groups according to the age and compared brain perfusion respectively. In patient below fifties, brain perfusion in both occipitoparietal and left temporal lobe were lower in PD group. As the patients with PD grew older, hypoperfusion area were shown in both frontal, temporal and limbic lobes. Fourthly, We were able to divide patients into small groups based on cerebral perfusion pattern. There was normal cerebral blood

  5. 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.)

  6. In vitro and in vivo studies of Allium sativum extract against deltamethrin-induced oxidative stress in rats brain and kidney.

    Science.gov (United States)

    Ncir, Marwa; Saoudi, Mongi; Sellami, Hanen; Rahmouni, Fatma; Lahyani, Amina; Makni Ayadi, Fatma; El Feki, Abdelfattah; Allagui, Mohamed Salah

    2017-09-18

    The present study investigated the in vitro and the in vivo antioxidant capacities of Allium sativum (garlic) extract against deltamethrin-induced oxidative damage in rat's brain and kidney. The in vitro result showed that highest extraction yield was achieved with methanol (20.08%). Among the tested extracts, the methanol extract exhibited the highest total phenolic, flavonoids contents and antioxidant activity. The in vivo results showed that deltamethrin treatment caused an increase of the acetylcholinesterase level (AChE) in brain and plasma, the brain and kidney conjugated dienes and lipid peroxidation (LPO) levels as compared to control group. The antioxidant enzymes results showed that deltamethrin treatment induced a significantly decrease (p < 0.01) in brain and kidney antioxidant enzymes as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) to control group. The co-administration of garlic extract reduced the toxic effects in brain and kidney tissues induced by deltamethrin.

  7. Age-dependent complex noise fluctuations in the brain

    International Nuclear Information System (INIS)

    Mareš, Jan; Vyšata, Oldřich; Procházka, Aleš; Vališ, Martin

    2013-01-01

    We investigated the parameters of colored noise in EEG data of 17 722 professional drivers aged 18–70. The whole study is based upon experiments showing that biological neural networks may operate in the vicinity of the critical point and that the balance between excitation and inhibition in the human brain is important for the transfer of information. This paper is devoted to the study of EEG power spectrum which can be described best by a power function with 1/f λ distribution and colored noise corresponding to the critical point in the EEG signal has the value of λ = 1 (purple noise). The slow accumulation of energy and its quick release is a universal property of the 1/f distribution. The physiological mechanism causing energy dissipation in the brain seems to depend on the number and strength of the connections between clusters of neurons. With ageing, the number of connections between the neurons decreases. Learning ability and intellectual performance also decrease. Therefore, age-related changes in the λ coefficient can be anticipated. We found that absolute values of λ coefficients decrease significantly with increasing age. Deviations from this rule are related to age-dependent slowing of the dominant frequency in the alpha band. Age-dependent change in the parameter and colored noise may be indicative of age-related changes in the self-organization of brain activity. Results obtained include (i) the age-dependent decrease of the absolute values of the average λ coefficient with the regression coefficient 0.005 1/year, (ii) distribution of λ value changes related to EEG frequency bands and to localization of electrodes on the scalp, and (iii) relation of age-dependent changes of colored noise and EEG energy in separate frequency bands. (paper)

  8. Tributyltin exposure causes brain damage in Sebastiscus marmoratus.

    Science.gov (United States)

    Zhang, Jiliang; Zuo, Zhenghong; Chen, Rong; Chen, Yixin; Wang, Chonggang

    2008-09-01

    Tributyltin (TBT) is a ubiquitous marine environmental contaminant characterized primarily by its reproductive toxicity. However, the neurotoxic effect of TBT has not been extensively described, especially in fishes which have a high number of species in the marine environment. This study was conducted to investigate the neurotoxic effects of TBT at environmental levels (1, 10, and 100ngl(-1)) on female Sebastiscus marmoratus. The results showed that TBT exposure induced apoptosis in brain cells of three regions including the pallial areas of the telencephalon, the granular layer of the optic tectum, and the cerebellum. In addition, the increase of reactive oxygen species and nitric oxide levels, and the decrease of Na+/K+-ATPase activity were found in the brain. The results strongly indicated neurotoxicity of TBT to fishes. According to the regions in which apoptosis was found in the brain, TBT exposure might influence the schooling, sensory and motorial functions of fishes.

  9. Brain metastasis from colorectal cancer

    International Nuclear Information System (INIS)

    Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo

    2007-01-01

    The present study was performed to clarify the clinical characteristics of brain metastasis from colorectal cancer. Five patients with brain metastasis from colorectal cancer treated at our institute between 2001 and 2005 were included in the study. Clinical findings and survival time were determined and an appropriate system for follow-up in such cases was considered. Brain metastasis was found after surgery for colorectal cancer in 4 cases. In addition, colorectal cancer was found after diagnosis of brain metastasis in 1 case. At the time of diagnosis of brain metastasis, all patients had lung metastasis and 3 had liver metastasis. The mean periods between surgery for colorectal cancer and lung and brain metastases were 19.5 and 38.2 months, respectively. In all cases, brain metastasis was diagnosed by imaging after the appearance of neurological symptoms. Brain metastases were multiple in 1 case and focal in 4 cases. We performed gamma knife radiation therapy, and the symptoms disappeared or decreased in all cases. Mean survival time after brain metastasis was 3.0 months. Prognosis after brain metastasis is poor, but gamma knife radiation therapy contributed to patients' quality of life. (author)

  10. Decreased alternative splicing of estrogen receptor-α mRNA in the Alzheimer's disease brain

    NARCIS (Netherlands)

    Ishunina, Tatjana A.; Swaab, Dick F.

    2012-01-01

    In this study we identified 62 estrogen receptor alpha (ERα) mRNA splice variants in different human brain areas of Alzheimer's disease (AD) and control cases and classified them into 12 groups. Forty-eight of these splice forms were identified for the first time. The distribution of alternatively

  11. Brain viscoelasticity alteration in chronic-progressive multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Kaspar-Josche Streitberger

    Full Text Available INTRODUCTION: Viscoelastic properties indicate structural alterations in biological tissues at multiple scales with high sensitivity. Magnetic Resonance Elastography (MRE is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. MRE recently revealed that early relapsing-remitting multiple sclerosis (MS is associated with a global decrease of the cerebral mechanical integrity. This study addresses MRE and MR volumetry in chronic-progressive disease courses of MS. METHODS: We determined viscoelastic parameters of the brain parenchyma in 23 MS patients with primary or secondary chronic progressive disease course in comparison to 38 age- and gender-matched healthy individuals by multifrequency MRE, and correlated the results with clinical data, T2 lesion load and brain volume. Two viscoelastic parameters, the shear elasticity μ and the powerlaw exponent α, were deduced according to the springpot model and compared to literature values of relapsing-remitting MS. RESULTS: In chronic-progressive MS patients, μ and α were reduced by 20.5% and 6.1%, respectively, compared to healthy controls. MR volumetry yielded a weaker correlation: Total brain volume loss in MS patients was in the range of 7.5% and 1.7% considering the brain parenchymal fraction. All findings were significant (P<0.001. CONCLUSIONS: Chronic-progressive MS disease courses show a pronounced reduction of the cerebral shear elasticity compared to early relapsing-remitting disease. The powerlaw exponent α decreased only in the chronic-progressive stage of MS, suggesting an alteration in the geometry of the cerebral mechanical network due to chronic neuroinflammation.

  12. Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1.

    Science.gov (United States)

    Seillier, Lenka; Lorenz, Corinna; Kawaguchi, Katsuhisa; Ott, Torben; Nieder, Andreas; Pourriahi, Paria; Nienborg, Hendrikje

    2017-11-22

    Serotonin, an important neuromodulator in the brain, is implicated in affective and cognitive functions. However, its role even for basic cortical processes is controversial. For example, in the mammalian primary visual cortex (V1), heterogenous serotonergic modulation has been observed in anesthetized animals. Here, we combined extracellular single-unit recordings with iontophoresis in awake animals. We examined the role of serotonin on well-defined tuning properties (orientation, spatial frequency, contrast, and size) in V1 of two male macaque monkeys. We find that in the awake macaque the modulatory effect of serotonin is surprisingly uniform: it causes a mainly multiplicative decrease of the visual responses and a slight increase in the stimulus-selective response latency. Moreover, serotonin neither systematically changes the selectivity or variability of the response, nor the interneuronal correlation unexplained by the stimulus ("noise-correlation"). The modulation by serotonin has qualitative similarities with that for a decrease in stimulus contrast, but differs quantitatively from decreasing contrast. It can be captured by a simple additive change to a threshold-linear spiking nonlinearity. Together, our results show that serotonin is well suited to control the response gain of neurons in V1 depending on the animal's behavioral or motivational context, complementing other known state-dependent gain-control mechanisms. SIGNIFICANCE STATEMENT Serotonin is an important neuromodulator in the brain and a major target for drugs used to treat psychiatric disorders. Nonetheless, surprisingly little is known about how it shapes information processing in sensory areas. Here we examined the serotonergic modulation of visual processing in the primary visual cortex of awake behaving macaque monkeys. We found that serotonin mainly decreased the gain of the visual responses, without systematically changing their selectivity, variability, or covariability. This

  13. Minocycline Attenuates Iron-Induced Brain Injury.

    Science.gov (United States)

    Zhao, Fan; Xi, Guohua; Liu, Wenqaun; Keep, Richard F; Hua, Ya

    2016-01-01

    Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism.

  14. Aluminum neurotoxicity in the rat brain

    International Nuclear Information System (INIS)

    Yumoto, S.; Ohashi, H.; Nagai, H.; Kakimi, S.; Ogawa, Y.; Iwata, Y.; Ishii, K.

    1992-01-01

    To investigate the etiology of Alzheimer's disease, we administered aluminum to healthy rats and examined the aluminum uptake in the brain and isolated brain cell nuclei by particle-induced X-ray emission (PIXE) analysis. Ten days after the last injection, Al was detected in the rat brain and in isolated brain cell nuclei by PIXE analysis. Al was also demonstrated in the brain after 15 months of oral aluminum administration. Moreover, Al was detected in the brain and isolated brain cell nuclei from the patients with Alzheimer's disease. Silver impregnation studies revealed that spines attached to the dendritic processes of cortical nerve cells decreased remarkably after aluminum administration. Electron microscopy revealed characteristic inclusion bodies in the hippocampal nerve cells 75 days after the injection. These morphological changes in the rat brain after the aluminum administration were similar to those reportedly observed in the brain of Alzheimer's disease patients. Our results indicate that Alzheimer's disease is caused by irreversible accumulation of aluminum in the brain, as well as in the nuclei of brain cells. (author)

  15. Aluminum neurotoxicity in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Yumoto, S [Tokyo Univ. (Japan). Faculty of Medicine; Ohashi, H; Nagai, H; Kakimi, S; Ogawa, Y; Iwata, Y; Ishii, K

    1993-12-31

    To investigate the etiology of Alzheimer`s disease, we administered aluminum to healthy rats and examined the aluminum uptake in the brain and isolated brain cell nuclei by particle-induced X-ray emission (PIXE) analysis. Ten days after the last injection, Al was detected in the rat brain and in isolated brain cell nuclei by PIXE analysis. Al was also demonstrated in the brain after 15 months of oral aluminum administration. Moreover, Al was detected in the brain and isolated brain cell nuclei from the patients with Alzheimer`s disease. Silver impregnation studies revealed that spines attached to the dendritic processes of cortical nerve cells decreased remarkably after aluminum administration. Electron microscopy revealed characteristic inclusion bodies in the hippocampal nerve cells 75 days after the injection. These morphological changes in the rat brain after the aluminum administration were similar to those reportedly observed in the brain of Alzheimer`s disease patients. Our results indicate that Alzheimer`s disease is caused by irreversible accumulation of aluminum in the brain, as well as in the nuclei of brain cells. (author).

  16. The Brain Drain in Mexico--A Subject for Research...or Agenda?

    Science.gov (United States)

    Aupetit, Sylvie Didou

    2006-01-01

    The purpose of this article is to analyse the present state of the discussion and data regarding the brain drain in Mexico. From current data, recent trends show certain peculiarities in the national picture, pointing to an increase in the number of free movers, and a decrease in the number of young people who obtain Mexican government…

  17. Radiosurgery without whole brain radiotherapy in melanoma brain metastases

    International Nuclear Information System (INIS)

    Grob, J.J.; Regis, J.; Laurans, R.; Delaunay, M.; Wolkenstein, P.; Paul, K.; Souteyrand, P.; Koeppel, M.C.; Murraciole, X.; Perragut, J.C.; Bonerandi, J.J.

    1998-01-01

    To evaluate the effectiveness of radiosurgery without whole brain radiotherapy in the palliative treatment of melanoma brain metastases, we retrospectively assessed the results in 35 patients: 4 with a solitary brain metastasis, 13 with a single brain metastasis and metastases elsewhere and 18 with multiple brain metastases. The local control rate was 98.2% (55/56 metastases) at 3 months. Median survival was 22 months in patients with a solitary brain metastasis, 7.5 months in patients with a single brain metastasis and metastases elsewhere, and 4 months in patients with multiple brain metastases. Complications were unusual and surgery was required in 2 of 35 patients. These results show for the first time that melanoma patients with a unique brain metastasis with or without metastases elsewhere clearly benefit from tumour control easily obtained by radiosurgery. Although the comparison of radiosurgery with surgery and/or whole brain radiotherapy cannot be adequately addressed, radiosurgery alone seems to provide similar results with lower morbidity and impact on quality of life. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  18. 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.

  19. Novel G Protein-Coupled Oestrogen Receptor GPR30 Shows Changes in mRNA Expression in the Rat Brain over the Oestrous Cycle

    Directory of Open Access Journals (Sweden)

    Emma J. Spary

    2012-02-01

    Full Text Available Oestrogen influences autonomic function via actions at classical nuclear oestrogen receptors α and β in the brain, and recent evidence suggests the orphan G protein-coupled receptor GPR30 may also function as a cytoplasmic oestrogen receptor. We investigated the expression of GPR30 in female rat brains throughout the oestrous cycle and after ovariectomy to determine whether GPR30 expression in central autonomic nuclei is correlated with circulating oestrogen levels. In the nucleus of the solitary tract (NTS, ventrolateral medulla (VLM and periaqueductal gray (PAG GPR30 mRNA, quantified by real-time PCR, was increased in proestrus and oestrus. In ovariectomised (OVX rats, expression in NTS and VLM appeared increased compared to metoestrus, but in the hypothalamic paraventricular nucleus and PAG lower mRNA levels were seen in OVX. GPR30-like immunoreactivity (GPR30-LI colocalised with Golgi in neurones in many brain areas associated with autonomic pathways, and analysis of numbers of immunoreactive neurones showed differences consistent with the PCR data. GPR30-LI was found in a variety of transmitter phenotypes, including cholinergic, serotonergic, catecholaminergic and nitrergic neurones in different neuronal groups. These observations support the view that GPR30 could act as a rapid transducer responding to oestrogen levels and thus modulate the activity of central autonomic pathways.

  20. Developmental aspects of the rat brain insulin receptor: loss of sialic acid and fluctuation in number characterize fetal development

    International Nuclear Information System (INIS)

    Brennan, W.A. Jr.

    1988-01-01

    In this study, I have investigated the structure of the rat brain insulin receptor during fetal development. There is a progressive decrease in the apparent molecular size of the brain alpha-subunit during development: 130K on day 16 of gestation, 126K at birth, and 120K in the adult. Glycosylation was investigated as a possible reason for the observed differences in the alpha-subunit molecular size. The results show that the developmental decrease in the brain alpha-subunit apparent molecular size is due to a parallel decrease in sialic acid content. This was further confirmed by measuring the retention of autophosphorylated insulin receptors on wheat germ agglutinin (WGA)-Sepharose. An inverse correlation between developmental age and retention of 32 P-labeled insulin receptors on the lectin column was observed. Insulin binding increases 6-fold between 16 and 20 days of gestation [61 +/- 25 (+/- SE) fmol/mg protein and 364 +/- 42 fmol/mg, respectively]. Thereafter, binding in brain membranes decreases to 150 +/- 20 fmol/mg by 2 days after birth, then reaches the adult level of 63 +/- 15 fmol/mg. In addition, the degree of insulin-stimulated autophosphorylation closely parallels the developmental changes in insulin binding. Between 16 and 20 days of fetal life, insulin-stimulated phosphorylation of the beta-subunit increases 6-fold. Thereafter, the extent of phosphorylation decreases rapidly, reaching adult values identical with those in 16-day-old fetal brain. These results suggest that the embryonic brain possesses competent insulin receptors whose expression changes markedly during fetal development. This information should be important in defining the role of insulin in the developing nervous system

  1. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

    Science.gov (United States)

    Li, Guangye; Zhang, Dingguo

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain.

  2. Inside the Diabetic Brain

    Directory of Open Access Journals (Sweden)

    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.

  3. Stimulating the Right Temporoparietal Junction with tDCS Decreases Deception in Moral Hypocrisy and Unfairness

    Directory of Open Access Journals (Sweden)

    Honghong Tang

    2017-11-01

    Full Text Available Self-centered and other-regarding concerns play important roles in decisions of deception. To investigate how these two motivations affect deception in fairness related moral hypocrisy, we modulated the brain activity in the right temporoparietal junction (rTPJ, the key region for decision making involved in self-centered and other-regarding concerns. After receiving brain stimulation with transcranial direct current stimulation (tDCS, participants finished a modified dictator game. In the game, they played as proposers to make allocations between themselves and recipients and had a chance to deceive by misreporting their totals for allocations. Results show that deception in moral hypocrisy was decreased after anodal stimulation than sham and cathodal stimulation, only when participants know that their reported totals (appearing fair would be revealed to recipients rather than being unrevealed. Anodal stimulation also increased offers to recipients than cathodal stimulation regardless of the revelation of reported totals. These findings suggest that enhancing the activity of rTPJ decreased deception caused by impression management rather than self-deception in moral hypocrisy and unfairness through facilitating other-regarding concerns and weakening non-material self-centered motivations. They provide causal evidence for the role of rTPJ in both other-regarding concerns and non-material self-centered motivations, shedding light on the way to decrease moral hypocrisy.

  4. Brain hypoperfusion on Tc-99m-ethylene dicysteine diethyl ester single-photon emission computed tomography in Hashimoto's encephalopathy

    OpenAIRE

    Grande, Mar?a Luz Dom?nguez; Constantino, Ana; Rayo, Juan Ignacio; Serrano, Justo; Infante, Jose Rafael; Garcia, Lucia; Duran, Carmen

    2013-01-01

    We present a 17-year-old female, previously diagnosed of autoimmune hyperthyroidism who had an acute neurological episode and presented high antithyroid antibodies titers, cerebral spinal fluid and electroencephalogram changes. Tc-99m ethylene dicysteine diethyl ester brain single-photon emission computed tomography (SPECT) showed global and patchy hypoperfusion. With glucocorticoid therapy, clinical symptoms disappeared; there was a decrease in antithyroid antibody levels and repeat brain SP...

  5. Wallerian degeneration of the corticospinal tract in the brain stem

    International Nuclear Information System (INIS)

    Uchino, Akira; Onomura, Kentaro; Ohno, Masato

    1989-01-01

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

  6. Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognitive responses in urban children.

    Directory of Open Access Journals (Sweden)

    Lilian eCalderon-Garciduenas

    2013-08-01

    Full Text Available Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-β diffuse plaques (compared to 0% in low pollution control children. We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1 and/or inflammatory mediators in MCMA children. Thirty g of dark cocoa with 680 mg of total flavonols were given daily for 10.11± 3.4 days (range 9 to 24 days to 18 children (10.55yrs, SD =1.45; 11F/7M. Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p=0.0002. Fifteen children (83% showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer’s and Parkinson’s diseases.

  7. Effects of low dose radiation pretreatment on radiation injuried brain's free radicle

    International Nuclear Information System (INIS)

    Xu Fuqi; Wang Cheng; Xie Hong; Tian Ye

    2006-01-01

    Objective: To investigate the effect of low dose radiation pretreatment on radiation in- juried brain's free radicle to provide some useful data of brain radiation injury protection. Methods: One hundred mGy was selected as the pretreatment does, 25 Gy was selected as the challenge does. Experiment rats were divided into three groups randomly, group one as simple group:the group irradiated without exposing to pre-irradiation; group two as 6 h-group: the group irradiated with LDR pretreatment 6 h before exposing to 25 Gy irradiation; group three as 24 h-group:the group irradiated with LDR pretreatment 24 h before 25 Gy irradiation. The observation was done 6 hour's after irradiation, the effect of LDR pretreatment on increasing activity of the superoxide dismutase(SOD) and the content of malondialdehyde(MDA) after the brain tissue homogenate were detected. Results: Com- pared with the simple group, the group with LDR pretreatment showed increasing of SOD and decreasing of MDA at the 6th hour after 25Gy irradiation. In addition, there was no difference between the 6 h-group and the 24 h-group. Conclusion: LDR pretreatment can increase SOD and decrease MDA in some period. It could infer that the suitable LDR pretreatment could play a protective role in the brain radiation injury. (authors)

  8. Brain involvement in patients with inflammatory bowel disease: a voxel-based morphometry and diffusion tensor imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Zikou, Anastasia K.; Astrakas, Loukas G.; Tzarouchi, Loukia C.; Argyropoulou, Maria I. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Kosmidou, Maria; Tsianos, Epameinondas [University of Ioannina, 1st Department of Internal Medicine (Hepato-Gastroenterology Unit), Medical School, Ioannina (Greece)

    2014-10-15

    To investigate structural brain changes in inflammatory bowel disease (IBD). Brain magnetic resonance imaging (MRI) was performed on 18 IBD patients (aged 45.16 ± 14.71 years) and 20 aged-matched control subjects. The imaging protocol consisted of a sagittal-FLAIR, a T1-weighted high-resolution three-dimensional spoiled gradient-echo sequence, and a multisession spin-echo echo-planar diffusion-weighted sequence. Differences between patients and controls in brain volume and diffusion indices were evaluated using the voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) methods, respectively. The presence of white-matter hyperintensities (WMHIs) was evaluated on FLAIR images. VBM revealed decreased grey matter (GM) volume in patients in the fusiform and the inferior temporal gyrus bilaterally, the right precentral gyrus, the right supplementary motor area, the right middle frontal gyrus and the left superior parietal gyrus (p < 0.05). TBSS showed decreased axial diffusivity (AD) in the right corticospinal tract and the right superior longitudinal fasciculus in patients compared with controls. A larger number of WMHIs was observed in patients (p < 0.05). Patients with IBD show an increase in WMHIs and GM atrophy, probably related to cerebral vasculitis and ischaemia. Decreased AD in major white matter tracts could be a secondary phenomenon, representing Wallerian degeneration. (orig.)

  9. Brain involvement in patients with inflammatory bowel disease: a voxel-based morphometry and diffusion tensor imaging study

    International Nuclear Information System (INIS)

    Zikou, Anastasia K.; Astrakas, Loukas G.; Tzarouchi, Loukia C.; Argyropoulou, Maria I.; Kosmidou, Maria; Tsianos, Epameinondas

    2014-01-01

    To investigate structural brain changes in inflammatory bowel disease (IBD). Brain magnetic resonance imaging (MRI) was performed on 18 IBD patients (aged 45.16 ± 14.71 years) and 20 aged-matched control subjects. The imaging protocol consisted of a sagittal-FLAIR, a T1-weighted high-resolution three-dimensional spoiled gradient-echo sequence, and a multisession spin-echo echo-planar diffusion-weighted sequence. Differences between patients and controls in brain volume and diffusion indices were evaluated using the voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) methods, respectively. The presence of white-matter hyperintensities (WMHIs) was evaluated on FLAIR images. VBM revealed decreased grey matter (GM) volume in patients in the fusiform and the inferior temporal gyrus bilaterally, the right precentral gyrus, the right supplementary motor area, the right middle frontal gyrus and the left superior parietal gyrus (p < 0.05). TBSS showed decreased axial diffusivity (AD) in the right corticospinal tract and the right superior longitudinal fasciculus in patients compared with controls. A larger number of WMHIs was observed in patients (p < 0.05). Patients with IBD show an increase in WMHIs and GM atrophy, probably related to cerebral vasculitis and ischaemia. Decreased AD in major white matter tracts could be a secondary phenomenon, representing Wallerian degeneration. (orig.)

  10. Fetal hypothalamic transplants into brain irradiated rats: Graft morphometry and host behavioral responses

    International Nuclear Information System (INIS)

    Pearlman, S.H.; Rubin, P.; White, H.C.; Wiegand, S.J.; Gash, D.M.

    1990-01-01

    This study was designed to test the hypothesis that neural implants can ameliorate or prevent some of the long-term changes associated with CNS irradiation. Using a rat model, the initial study focused on establishing motor, regulatory, and morphological changes associated with brain radiation treatments. Secondly, fetal hypothalamic tissue grafts were placed into the third ventricle of rats which had been previously irradiated. Adult male Long Evans rats received one of three radiation doses (15, 22.5, ampersand 30 Gy) or no radiation. Three days after irradiation, 7 animals in each dose group received an embryonic day 17 hypothalamic graft into the third ventricle while the remaining 8-9 animals in each group received injections of vehicle solution (sham). Few changes were observed in the 15 and 22.5 Gy animals, however rats in the 30 Gy treatment group showed stereotypic and ambulatory behavioral hyperactivity 32 weeks after irradiation. Regulatory changes in the high dose group included decreased growth rate and decreased urine osmolalities, but these measures were extremely variable among animals. Morphological results demonstrated that 30 Gy irradiated animals showed extensive necrosis primarily in the fimbria, which extended into the internal capsule, optic nerve, hippocampus, and thalamus. Hemorrhages were found in the hippocampus, thalamus, and fimbria. Defects in the blood-brain barrier also were evident by entry of intravascularly injected horseradish peroxidase into the parenchyma of the brain. Animals in the 30 Gy grafted group showed fewer behavioral changes and less brain damage than their sham grafted counterparts. Specifically, activity measures were comparable to normal levels, and a dilute urine was not found in the 30 Gy implanted rats. Morphological changes support these behavioral results since only two 30 Gy implanted rats showed necrosis

  11. Radiation-induced brain injury: A review

    Directory of Open Access Journals (Sweden)

    Michael eRobbins

    2012-07-01

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

  12. Autistic adolescents show atypical activation of the brain's mentalizing system even without a prior history of mentalizing problems.

    Science.gov (United States)

    White, Sarah J; Frith, Uta; Rellecke, Julian; Al-Noor, Zainab; Gilbert, Sam J

    2014-04-01

    Some autistic children pass classic Theory of Mind (ToM) tasks that others fail, but the significance of this finding is at present unclear. We identified two such groups of primary school age (labelled ToM+ and ToM-) and a matched comparison group of typically developing children (TD). Five years later we tested these participants again on a ToM test battery appropriate for adolescents and conducted an fMRI study with a story based ToM task. We also assessed autistic core symptoms at these two time points. At both times the ToM- group showed more severe social communication impairments than the ToM+ group, and while showing an improvement in mentalizing performance, they continued to show a significant impairment compared to the NT group. Two independent ROI analyses of the BOLD signal showed activation of the mentalizing network including medial prefrontal cortex, posterior cingulate and lateral temporal cortices. Strikingly, both ToM+ and ToM- groups showed very similar patterns of heightened activation in comparison with the NT group. No differences in other brain regions were apparent. Thus, autistic adolescents who do not have a history of mentalizing problems according to our ToM battery showed the same atypical neurophysiological response during mentalizing as children who did have such a history. This finding indicates that heterogeneity at the behavioural level may nevertheless map onto a similar phenotype at the neuro-cognitive level. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Endovascular treatment of brain-stem arteriovenous malformations: safety and efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, H.M.; Wang, Y.H.; Chen, Y.F.; Huang, K.M. [Department of Medical Imaging, National Taiwan University Hospital, 7 Chung-Shan South Road, 10016, Taipei (Taiwan); Tu, Y.K. [Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, 7 Chung-Shan South Road, 1001, Taipei (Taiwan)

    2003-09-01

    Our purpose was to evaluate the safety and efficacy of endovascular treatment of brain-stem arteriovenous malformations (AVMs), reviewing six cases managed in the last 5 years. There were four patients who presented with bleeding, one with a progressive neurological deficit and one with obstructive hydrocephalus. Of the six patients, one showed 100%, one 90%, two 75% and two about 50% angiographic obliteration of the AVM after embolisation; the volume decreased about 75% on average. Five patients had a good outcome and one an acceptable outcome, with a mild postprocedure neurological deficit; none had further bleeding during midterm follow-up. Endovascular management of a brain-stem AVM may be an alternative to treatment such as radiosurgery and microsurgery in selected cases. It may be not as risky as previously thought. Embolisation can reduce the size of the AVM and possibly make it more treatable by radiosurgery and decrease the possibility of radiation injury. (orig.)

  14. Vitamin-C protect ethanol induced apoptotic neuro degeneration in postnatal rat brain

    International Nuclear Information System (INIS)

    Naseer, M.I.; Najeebullah; Ikramullah; Zubair, H.; Hassan, M.; Yang, B.C.

    2010-01-01

    Objective: To evaluate ethanol effects to induced activation of caspsae-3, and to observe the protective effects of Vitamin C (vit-C) on ethanol-induced apoptotic neuro degeneration in rat cortical area of brain. Methodology: Administration of a single dose of ethanol in 7-d postnatal (P7) rats triggers activation of caspase-3 and widespread apoptotic neuronal death. Western blot analysis, cells counting and Nissl staining were used to elucidate possible protective effect of vit-C against ethanol-induced apoptotic neuro degeneration in brain. Results: The results showed that ethanol significantly increased caspase-3 expression and neuronal apoptosis. Furthermore, the co-treatment of vit-C along with ethanol showed significantly decreased expression of caspase-3 as compare to control group. Conclusion: Our findings indicate that vit-C can prevent some of the deleterious effect of ethanol on developing rat brain when given after ethanol exposure and can be used as an effective protective agent for Fetal Alcohol Syndrome (FAS). (author)

  15. Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity.

    Science.gov (United States)

    Matsui, Takashi; Omuro, Hideki; Liu, Yu-Fan; Soya, Mariko; Shima, Takeru; McEwen, Bruce S; Soya, Hideaki

    2017-06-13

    Brain glycogen stored in astrocytes provides lactate as an energy source to neurons through monocarboxylate transporters (MCTs) to maintain neuronal functions such as hippocampus-regulated memory formation. Although prolonged exhaustive exercise decreases brain glycogen, the role of this decrease and lactate transport in the exercising brain remains less clear. Because muscle glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays an energetic role in the prolonged-exercising brain to maintain endurance capacity through lactate transport. To test this hypothesis, we used a rat model of exhaustive exercise and capillary electrophoresis-mass spectrometry-based metabolomics to observe comprehensive energetics of the brain (cortex and hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted but brain glycogen was only decreased. The levels of MCT2, which takes up lactate in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed that brain, but not muscle, ATP was maintained with lactate and other glycogenolytic/glycolytic sources. Intracerebroventricular injection of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol did not affect peripheral glycemic conditions but suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, α-cyano-4-hydroxy-cinnamate, triggered a similar response that resulted in lower endurance capacity. These findings provide direct evidence for the energetic role of astrocytic glycogen-derived lactate in the exhaustive-exercising brain, implicating the significance of brain glycogen level in endurance capacity. Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons in the exhausted brain.

  16. The effects of short term and chronic exposure to tritiated drinking water on pre- and postnatal brain development

    International Nuclear Information System (INIS)

    Marthens, E. van; Zamenhof, S.

    1982-01-01

    Ingestion of HTO during oocyte maturation and continued during pre-implantation time was found to depress decidual response. At birth these offspring also showed a decrease in brain cell number. When HTO was given during pregnancy only, the offspring at birth showed a similar deficit in brain cell number. Even so, we could not demonstrate a gross deficit in oocyte maturation when HTO was ingested during sexual maturity only; however, when further continued during pregnancy, the measured newborn parameters were most severely affected. In this group, cell-multiplication in the cerebrum was severely decreased, protein synthesis was decreased, and somatic growth was also highly significantly decreased. These experiments indicate that even a short-term exposure to HTO during early pregnancy (pre-implantation) alters normal development to such an extent that it is still observable at birth. During embryonic development, HTO affected the rate of actual cell division and it is apparent that the central nervous system is most vulnerable. If the exposure to HTO is prolonged, the somatic development is also severely affected. (orig./MG)

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

    Directory of Open Access Journals (Sweden)

    De-An Zhao

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

  18. Decreased sound tolerance: hyperacusis, misophonia, diplacousis, and polyacousis.

    Science.gov (United States)

    Jastreboff, Pawel J; Jastreboff, Margaret M

    2015-01-01

    Definitions, potential mechanisms, and treatments for decreased sound tolerance, hyperacusis, misophonia, and diplacousis are presented with an emphasis on the associated physiologic and neurophysiological processes and principles. A distinction is made between subjects who experience these conditions versus patients who suffer from them. The role of the limbic and autonomic nervous systems and other brain systems involved in cases of bothersome decreased sound tolerance is stressed. The neurophysiological model of tinnitus is outlined with respect to how it may contribute to our understanding of these phenomena and their treatment. © 2015 Elsevier B.V. All rights reserved.

  19. Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

    Directory of Open Access Journals (Sweden)

    Eric J. Neuberger

    2017-09-01

    Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

  20. Progressively Disrupted Brain Functional Connectivity Network in Subcortical Ischemic Vascular Cognitive Impairment Patients.

    Science.gov (United States)

    Sang, Linqiong; Chen, Lin; Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Li, Chuanming; Qiu, Mingguo

    2018-01-01

    Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC > SIVCIND > SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p  impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.

  1. 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.)

  2. Preliminary application of brain perfusion SPECT imaging in schizophrenia

    International Nuclear Information System (INIS)

    Wu Zhixing; Guo Chanliu; Li Xingbao; Liang Rongxiang; Zhao Jun; Yan Tingxiu

    1996-01-01

    The clinical value of 99m Tc-ECD brain perfusion SPECT imaging was evaluated in patients with schizophrenia. 32 patients with schizophrenia and 21 normal controls were analyzed with 99m Tc-ECD SPECT. 93.8% (30/32) of the patients showed decreased regional cerebral blood flow (rCBF). There was normal rCBF in controls. In the patient group rCBF decreased significantly in bilateral frontal lobes, left temporal lobe and right basal ganglion. The rCBF of left temporal lobe was significantly lower than that of right temporal lobe. The decreasing rCBF was not significantly related to previous treatment and duration of illness. 99m Tc-ECD SPECT is useful for the study and diagnosis of patients with schizophrenia

  3. Brain-computer interfaces

    DEFF Research Database (Denmark)

    Treder, Matthias S.; Miklody, Daniel; Blankertz, Benjamin

    quality measure'. We were able to show that for stimuli close to the perceptual threshold, there was sometimes a discrepancy between overt responses and brain responses, shedding light on subjects using different response criteria (e.g., more liberal or more conservative). To conclude, brain-computer...... of perceptual and cognitive biases. Furthermore, subjects can only report on stimuli if they have a clear percept of them. On the other hand, the electroencephalogram (EEG), the electrical brain activity measured with electrodes on the scalp, is a more direct measure. It allows us to tap into the ongoing neural...... auditory processing stream. In particular, it can tap brain processes that are pre-conscious or even unconscious, such as the earliest brain responses to sounds stimuli in primary auditory cortex. In a series of studies, we used a machine learning approach to show that the EEG can accurately reflect...

  4. Oxidative stress induces the decline of brain EPO expression in aging rats.

    Science.gov (United States)

    Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

    2016-10-01

    Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of β-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (paging rats, the expressions of EPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (paging could result in the decline of EPO in the hippocampus and oxidative stress might be the main reason for the decline of brain EPO in aging rats, involved with the decrease of HIF-2α stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Age-related reduction of adaptive brain response during semantic integration is associated with gray matter reduction.

    Directory of Open Access Journals (Sweden)

    Zude Zhu

    Full Text Available While aging is associated with increased knowledge, it is also associated with decreased semantic integration. To investigate brain activation changes during semantic integration, a sample of forty-eight 25-75 year-old adults read sentences with high cloze (HC and low cloze (LC probability while functional magnetic resonance imaging was conducted. Significant age-related reduction of cloze effect (LC vs. HC was found in several regions, especially the left middle frontal gyrus (MFG and right inferior frontal gyrus (IFG, which play an important role in semantic integration. Moreover, when accounting for global gray matter volume reduction, the age-cloze correlation in the left MFG and right IFG was absent. The results suggest that brain structural atrophy may disrupt brain response in aging brains, which then show less brain engagement in semantic integration.

  6. Intranasal insulin modulates intrinsic reward and prefrontal circuitry of the human brain in lean women.

    Science.gov (United States)

    Kullmann, Stephanie; Frank, Sabine; Heni, Martin; Ketterer, Caroline; Veit, Ralf; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

    2013-01-01

    There is accumulating evidence that food consumption is controlled by a wide range of brain circuits outside of the homeostatic system. Activation in these brain circuits may override the homeostatic system and also contribute to the enormous increase of obesity. However, little is known about the influence of hormonal signals on the brain's non-homeostatic system. Thus, selective insulin action in the brain was investigated by using intranasal application. We performed 'resting-state' functional magnetic resonance imaging in 17 healthy lean female subjects to assess intrinsic brain activity by fractional amplitude of low-frequency fluctuations (fALFF) before, 30 and 90 min after application of intranasal insulin. Here, we showed that insulin modulates intrinsic brain activity in the hypothalamus and orbitofrontal cortex. Furthermore, we could show that the prefrontal and anterior cingulate cortex response to insulin is associated with body mass index. This demonstrates that hormonal signals as insulin may reduce food intake by modifying the reward and prefrontal circuitry of the human brain, thereby potentially decreasing the rewarding properties of food. Due to the alarming increase in obesity worldwide, it is of great importance to identify neural mechanisms of interaction between the homeostatic and non-homeostatic system to generate new targets for obesity therapy. Copyright © 2012 S. Karger AG, Basel.

  7. Continuous EEG-SEP monitoring in severe brain injury.

    Science.gov (United States)

    Amantini, A; Fossi, S; Grippo, A; Innocenti, P; Amadori, A; Bucciardini, L; Cossu, C; Nardini, C; Scarpelli, S; Roma, V; Pinto, F

    2009-04-01

    To monitor acute brain injury in the neurological intensive care unit (NICU), we used EEG and somatosensory evoked potentials (SEP) in combination to achieve more accuracy in detecting brain function deterioration. Sixty-eight patients (head trauma and intracranial hemorrhage; GCSSEP and intracranial pressure monitoring (ICP). Fifty-five patients were considered "stable" or improving, considering the GCS and CT scan: in this group, SEP didn't show significant changes. Thirteen patients showed neurological deteriorations and, in all patients, cortical SEP showed significant alterations (amplitude decrease>50% often till complete disappearance). SEP deterioration anticipated ICP increase in 30%, was contemporary in 38%, and followed ICP increase in 23%. Considering SEP and ICP in relation to clinical course, all patients but one with ICP less than 20 mmHg were stable, while the three patients with ICP greater than 40 mmHg all died. Among the 26 patients with ICP of 20-40 mmHg, 17 were stable, while nine showed clinical and neurophysiological deterioration. Thus, there is a range of ICP values (20-40 mmHg) were ICP is scarcely indicative of clinical deterioration, rather it is the SEP changes that identify brain function deterioration. Therefore, SEP have a twofold interest with respect to ICP: their changes can precede an ICP increase and they can constitute a complementary tool to interpret ICP trends. It has been very important to associate SEP and EEG: about 60% of our patients were deeply sedated and, because of their relative insensitivity to anesthetics, only SEP allowed us to monitor brain damage evolution when EEG was scarcely valuable. We observed 3% of nonconvulsive status epilepticus compared to 18% of neurological deterioration. If the aim of neurophysiological monitoring is to "detect and protect", it may not be limited to detecting seizures, rather it should be able to identify brain deterioration, so we propose the combined monitoring of EEG with SEP.

  8. Fast and robust multi-atlas segmentation of brain magnetic resonance images

    DEFF Research Database (Denmark)

    Lötjönen, Jyrki Mp; Wolz, Robin; Koikkalainen, Juha R

    2010-01-01

    We introduce an optimised pipeline for multi-atlas brain MRI segmentation. Both accuracy and speed of segmentation are considered. We study different similarity measures used in non-rigid registration. We show that intensity differences for intensity normalised images can be used instead of stand......We introduce an optimised pipeline for multi-atlas brain MRI segmentation. Both accuracy and speed of segmentation are considered. We study different similarity measures used in non-rigid registration. We show that intensity differences for intensity normalised images can be used instead...... of standard normalised mutual information in registration without compromising the accuracy but leading to threefold decrease in the computation time. We study and validate also different methods for atlas selection. Finally, we propose two new approaches for combining multi-atlas segmentation and intensity...

  9. Herpes zoster chronification to postherpetic neuralgia induces brain activity and grey matter volume change

    Science.gov (United States)

    Cao, Song; Qin, Bangyong; Zhang, Yi; Yuan, Jie; Fu, Bao; Xie, Peng; Song, Ganjun; Li, Ying; Yu, Tian

    2018-01-01

    Objective: Herpes zoster (HZ) can develop into postherpetic neuralgia (PHN), which is a chronic neuropathic pain (NP). Whether the chronification from HZ to PHN induced brain functional or structural change is unknown and no study compared the changes of the same brains of patients who transited from HZ to PHN. We minimized individual differences and observed whether the chronification of HZ to PHN induces functional and pain duration dependent grey matter volume (GMV) change in HZ-PHN patients. Methods: To minimize individual differences induced error, we enrolled 12 patients with a transition from HZ to PHN. The functional and structural changes of their brains between the two states were identified with resting-state functional MRI (rs-fMRI) technique (i.e., the regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) method) and the voxel based morphometry (VBM) technology respectively. The correlations between MRI parameters (i.e., ΔReHo, ΔfALFF and ΔVBM) and Δpain duration were analyzed too. Results: Compared with HZ brains, PHN brains exhibited abnormal ReHo, fALFF and VBM values in pain matrix (the frontal lobe, parietal lobe, thalamus, limbic lobe and cerebellum) as well as the occipital lobe and temporal lobe. Nevertheless, the activity of vast area of cerebellum and frontal lobe significantly increased while that of occipital lobe and limbic lobe showed apparent decrease when HZ developed to PHN. In addition, PHN brain showed decreased GMV in the frontal lobe, the parietal lobe and the occipital lobe but increased in the cerebellum and the temporal lobe. Correlation analyses showed that some of the ReHo, fALFF and VBM differential areas (such as the cerebellum posterior lobe, the thalamus extra-nuclear and the middle temporal gyrus) correlated well with Δpain duration. Conclusions: HZ chronification induced functional and structural change in cerebellum, occipital lobe, temporal lobe, parietal lobe and limbic lobe

  10. 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...

  11. APPswe/PS1dE9 mice with cortical amyloid pathology show a reduced NAA/Cr ratio without apparent brain atrophy: A MRS and MRI study.

    Science.gov (United States)

    Kuhla, Angela; Rühlmann, Claire; Lindner, Tobias; Polei, Stefan; Hadlich, Stefan; Krause, Bernd J; Vollmar, Brigitte; Teipel, Stefan J

    2017-01-01

    Transgenic animal models of Aβ pathology provide mechanistic insight into some aspects of Alzheimer disease (AD) pathology related to Aβ accumulation. Quantitative neuroimaging is a possible aid to improve translation of mechanistic findings in transgenic models to human end phenotypes of brain morphology or function. Therefore, we combined MRI-based morphometry, MRS-based NAA-assessment and quantitative histology of neurons and amyloid plaque load in the APPswe/PS1dE9 mouse model to determine the interrelationship between morphological changes, changes in neuron numbers and amyloid plaque load with reductions of NAA levels as marker of neuronal functional viability. The APPswe/PS1dE9 mouse showed an increase of Aβ plaques, loss of neurons and an impairment of NAA/Cr ratio, which however was not accompanied with brain atrophy. As brain atrophy is one main characteristic in human AD, conclusions from murine to human AD pathology should be drawn with caution.

  12. Zinc movement in the brain under kainate-induced seizures.

    Science.gov (United States)

    Takeda, Atsushi; Hirate, Maki; Tamano, Haruna; Oku, Naoto

    2003-05-01

    On the basis of the evidence that elimination of 65Zn from the brain of epilepsy (EL) mice is facilitated by induction of seizures, zinc movement in the brain was studied in mice injected with kainate (12 mg/kg x 3), which exhibited status epilepticus within 120 min after the last injection of kainate. Zinc concentrations in the brain were determined 24 h after the last injection of kainate. Zinc concentrations in the hippocampus, amygdala and cerebral cortex, in which zinc-containing glutamatergic neuron terminals exist, were significantly decreased by the treatment with kainate, while that in the cerebellum was not decreased. Timm's stain in the brain was extensively attenuated 24 h after the last injection of kainate. These results indicate that zinc homeostasis in the brain is affected by kainate-induced seizures. In the hippocampus of rats injected with kainate (10 mg/kg), furthermore, the release of zinc and glutamate into the extracellular fluid was studied using in vivo microdialysis. The levels of zinc and glutamate in the perfusate were increased along with seizure severity after injection of kainate. It is likely that zinc concentration in the synaptic vesicles is decreased by the excess excitation of glutamatergic neurons. The present study suggests that the excessive release of zinc and glutamate from the neuron terminals under kainate-induced seizures is associated with the loss of zinc from the brain.

  13. Possible effects of rosuvastatin on noise-induced oxidative stress in rat brain

    Directory of Open Access Journals (Sweden)

    Alevtina Ersoy

    2014-01-01

    Full Text Available The problem of noise has recently gained more attention as it has become an integral part of our daily lives. However, its influence has yet to be fully elucidated. Other than being an unpleasant stimulus, noise may cause health disorders through annoyance and stress, including oxidative stress. Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, may possess antioxidant properties. Based on rat models, our project investigates the effect of rosuvastatin on noise-induced oxidative stress in the brain tissue. Thirty-two male Wistar albino rats were used. The rats were divided into four groups: Noise exposure plus rosuvastatin usage, only noise exposure, only rosuvastatin usage, and control. After the data had been collected, oxidant and antioxidant parameters were analyzed in the cerebral cortex, brain stem, and cerebellum. Results indicated that superoxide dismutase values were significantly decreased in the cerebral cortex, while malondialdehyde values in the brainstem and cerebellum were significantly increased in the group with only noise exposure. Superoxide dismutase values in the brainstem were significantly increased, but nitric oxide values in the cerebellum and brainstem and malondialdehyde values in the cerebellum and cerebral cortex were significantly decreased in the group where only rosuvastatin was used. During noise exposure, the use of rosuvastatin caused significantly increased superoxide dismutase values in the cerebral cortex and brainstem, but significantly reduced malondialdehyde values in the brain stem. Consequently, our data show that brain tissue was affected by oxidative stress due to continued exposure to noise. This noise-induced stress decreases with rosuvastatin therapy.

  14. Structural and functional brain changes beyond visual system in patients with advanced glaucoma.

    Directory of Open Access Journals (Sweden)

    Paolo Frezzotti

    Full Text Available In order to test the hypothesis that in primary open angle glaucoma (POAG, an important cause of irreversible blindness, a spreading of neurodegeneration occurs through the brain, we performed multimodal MRI and subsequent whole-brain explorative voxelwise analyses in 13 advanced POAG patients and 12 age-matched normal controls (NC. Altered integrity (decreased fractional anisotropy or increased diffusivities of white matter (WM tracts was found not only along the visual pathway of POAG but also in nonvisual WM tracts (superior longitudinal fascicle, anterior thalamic radiation, corticospinal tract, middle cerebellar peduncle. POAG patients also showed brain atrophy in both visual cortex and other distant grey matter (GM regions (frontoparietal cortex, hippocampi and cerebellar cortex, decreased functional connectivity (FC in visual, working memory and dorsal attention networks and increased FC in visual and executive networks. In POAG, abnormalities in structure and FC within and outside visual system correlated with visual field parameters in the poorer performing eyes, thus emphasizing their clinical relevance. Altogether, this represents evidence that a vision disorder such as POAG can be considered a widespread neurodegenerative condition.

  15. Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

    OpenAIRE

    Najmeh Kabiri; Mahbubeh Setorki

    2016-01-01

    The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99). Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly hi...

  16. Effect of Sex Differences on Brain Mitochondrial Function and Its Suppression by Ovariectomy and in Aged Mice.

    Science.gov (United States)

    Gaignard, Pauline; Savouroux, Stéphane; Liere, Philippe; Pianos, Antoine; Thérond, Patrice; Schumacher, Michael; Slama, Abdelhamid; Guennoun, Rachida

    2015-08-01

    Sex steroids regulate brain function in both normal and pathological states. Mitochondria are an essential target of steroids, as demonstrated by the experimental administration of 17β-estradiol or progesterone (PROG) to ovariectomized female rodents, but the influence of endogenous sex steroids remains understudied. To address this issue, mitochondrial oxidative stress, the oxidative phosphorylation system, and brain steroid levels were analyzed under 3 different experimental sets of endocrine conditions. The first set was designed to study steroid-mediated sex differences in young male and female mice, intact and after gonadectomy. The second set concerned young female mice at 3 time points of the estrous cycle in order to analyze the influence of transient variations in steroid levels. The third set involved the evaluation of the effects of a permanent decrease in gonadal steroids in aged male and female mice. Our results show that young adult females have lower oxidative stress and a higher reduced nicotinamide adenine dinucleotide (NADH)-linked respiration rate, which is related to a higher pyruvate dehydrogenase complex activity as compared with young adult males. This sex difference did not depend on phases of the estrous cycle, was suppressed by ovariectomy but not by orchidectomy, and no longer existed in aged mice. Concomitant analysis of brain steroids showed that pregnenolone and PROG brain levels were higher in females during the reproductive period than in males and decreased with aging in females. These findings suggest that the major male/female differences in brain pregnenolone and PROG levels may contribute to the sex differences observed in brain mitochondrial function.

  17. The brain stem function in patients with brain bladder

    International Nuclear Information System (INIS)

    Takahashi, Toshihiro

    1990-01-01

    A syndrome of detrusor-sphincter dyssynergia (DSD) is occasionally found in patients with brain bladder. To evaluate the brain stem function in cases of brain bladder, urodynamic study, dynamic CT scan of the brain stem (DCT) and auditory brainstem response (ABR) were performed. The region of interest of DCT aimed at the posterolateral portion of the pons. The results were analysed in contrast with the presense of DSD in urodynamic study. DCT studies were performed in 13 cases with various brain diseases and 5 control cases without neurological diseases. Abnormal patterns of the time-density curve consisted of low peak value, prolongation of filling time and low rapid washout ratio (low clearance ratio) of the contrast medium. Four of 6 cases with DSD showed at least one of the abnormal patterns of the time-density curve bilaterally. In 7 cases without DSD none showed bilateral abnormality of the curve and in 2 of 7 cases only unilateral abnormality was found. ABR was performed in 8 patients with brain diseases. The interpeak latency of the wave I-V (I-V IPL) was considered to be prolonged in 2 cases with DSD compared to that of 4 without DSD. In 2 cases with DSD who had normal DCT findings, measurement of the I-V IPL was impossible due to abnormal pattern of the ABR wave. Above mentioned results suggests the presence of functional disturbance at the posterolateral portion of the pons in cases of brain bladder with DSD. (author)

  18. Brain insulin controls adipose tissue lipolysis and lipogenesis

    Science.gov (United States)

    Scherer, Thomas; O’Hare, James; Diggs-Andrews, Kelly; Schweiger, Martina; Cheng, Bob; Lindtner, Claudia; Zielinski, Elizabeth; Vempati, Prashant; Su, Kai; Dighe, Shveta; Milsom, Thomas; Puchowicz, Michelle; Scheja, Ludger; Zechner, Rudolf; Fisher, Simon J.; Previs, Stephen F.; Buettner, Christoph

    2011-01-01

    SUMMARY White adipose tissue (WAT) dysfunction plays a key role in the pathogenesis of type 2 diabetes (DM2). Unrestrained WAT lipolysis results in increased fatty acid release leading to insulin resistance and lipotoxicity, while impaired de novo lipogenesis in WAT decreases the synthesis of insulin sensitizing fatty acid species like palmitoleate. Here we show that insulin infused into the mediobasal hypothalamus (MBH) of Sprague Dawley rats increases WAT lipogenic protein expression, and inactivates hormone sensitive lipase (Hsl) and suppresses lipolysis. Conversely, mice that lack the neuronal insulin receptor exhibit unrestrained lipolysis and decreased de novo lipogenesis in WAT. Thus, brain and in particular hypothalamic insulin action play a pivotal role in WAT functionality. PMID:21284985

  19. Brain edema associated with unruptured brain arteriovenous malformations

    International Nuclear Information System (INIS)

    Kim, Bum-soo; Sarma, Dipanka; Lee, Seon-Kyu; ter Brugge, Karel G.

    2009-01-01

    Brain edema in unruptured brain arteriovenous malformations (AVMs) is rare; this study examines (1) its frequency and clinical presentation, (2) imaging findings with emphasis on venous drainage abnormalities, and (3) implications of these findings on natural history and management. Presentation and imaging features of all unruptured brain AVMs were prospectively collected in our brain AVM database. Neurological findings, size, location, venous drainage pattern, presence of venous thrombosis, ectasia, or stenosis, and brain edema were specifically recorded. Treatment details of all patients with brain edema and their clinical and imaging follow-up were reviewed. Finally, a comparison was made between patients with and without edema. Brain edema was found in 13/329 unruptured brain AVMs (3.9%). Neurological deficit (46.2%), venous thrombosis (38.5%), venous ectasia (84.6%), stenosis (38.5%), and contrast stagnation in the draining veins (84.6%) were more frequent in patients with brain edema than without edema. Eight patients with brain edema received specific treatment (embolization = 5, surgery = 2, radiosurgery = 1). Clinical features correlated well with change in degree of edema in six. Three of five embolized patients were stable or showed improvement after the procedure. On follow-up, however, intracranial hemorrhage developed in three. Brain edema in unruptured brain AVMs is rare, 3.9% in this series. Venous outflow abnormalities are frequently associated and appear to contribute to the development of edema. Progressive nonhemorrhagic symptoms are also associated, with a possible increased risk of hemorrhage. Palliative embolization arrests the nonhemorrhagic symptoms in selected patients, although it may not have an effect on hemorrhagic risk. (orig.)

  20. Hippotherapy and neurofeedback training effect on the brain function and serum brain-derived neurotrophic factor level changes in children with attention-deficit or/and hyperactivity disorder.

    Science.gov (United States)

    Lee, Namju; Park, Sok; Kim, Jongkyu

    2017-09-30

    The purpose of this study was to investigate the effect of hippotherapy and electroencephalography (EEG) neurofeedback on brain function and blood brain-derived neurotrophic factor (BDNF) level in children with attention-deficit or/and hyperactivity disorder (ADHD). Sixteen children with ADHD participated in this study and were randomly divided into 2 groups, a 1-time hippotherapy group (W1G, n = 8) and a 2-time hippotherapy group (W2G, n = 8). All the participants attended 8 weeks of hippotherapy program in the primary training, and then 7 children with ADHD attended 8 weeks of hippotherapy program combined with neurofeedback training in the secondary training. Blood BDNF levels were measured, and functional magnetic resonance imaging (fMRI) was performed. The EEG neurofeedback training program was used to train and measure psychological factors. The combined effect of hippotherapy and neurofeedback on BDNF level showed a decreased tendency in W1G (pretraining, 1766.03 ± 362.54 pg/ml; posttraining, 1630.65 ± 276.70 pg/ml). However, the BDNF level of W2G showed an increased tendency (pretraining, 1968.28 ± 429.08 pg/ml; posttraining, 1976.28 ± 425.35 pg/ml). Moreover, combined training showed a significant group x repetition interaction in W1G (pretraining, 1436.57 ± 368.76 pg/ml; posttraining, 1525.23 ± 346.22 pg/ml; F = 3.870, p = 0.039). fMRI results showed that the left thalamus activity in both groups had a decreased tendency and a significantly lower change in W2G than in W1G (p < 0.05). This study confirmed a significant increase in blood BDNF level after combined training, which may induce brain function improvement in children with ADHD. ©2017 The Korean Society for Exercise Nutrition

  1. Lower gingival squamous cell carcinoma with brain metastasis during long-term cetuximab treatment: A case report.

    Science.gov (United States)

    Naruse, Tomofumi; Tokuhisa, Mitsuko; Yanamoto, Souichi; Sakamoto, Yuki; Okuyama, Kohei; Tsuchihashi, Hiroki; Umeda, Masahiro

    2018-05-01

    Long-term cetuximab treatment can lead to acquired resistance, and tumor progression and/or new lesions often occur. The present report describes a case of lower gingival squamous cell carcinoma with brain metastasis during long-term cetuximab treatment in a 60-year-old man, including findings of an immunohistochemical study. The resected primary tumors, biopsy of the lung metastasis before administration of cetuximab, and brain metastasis specimens mediated by cetuximab were immunohistochemically examined. Histologically, the metastatic brain lesion showed hyperkeratinizing tumor cells with deeply stained irregular nuclei with necrotizing tumor cells, and a decrease in cell density was exhibited in part of the tumor nest. Moreover, the brain lesion was less malignant compared with the primary tumor and metastatic lung lesions. Immunohistochemically, the metastatic brain lesions showed low expression of epidermal growth factor receptor (EGFR) and high expression of N-cadherin compared with the primary tumor and metastatic lung lesions. These results suggest that acquired resistance to cetuximab may be associated with low EGFR expression and increased epithelial-to-mesenchymal transition potential.

  2. Brain abscess mimicking brain metastasis in breast cancer

    International Nuclear Information System (INIS)

    Khullar, P.; Datta, N.R.; Wahi, I.K.; Kataria, S.

    2016-01-01

    61 year old female presented with chief complaints of headache for 30 days, fever for 10 days, altered behavior for 10 days and convulsion for 2 days. She was diagnosed and treated as a case of carcinoma of left breast 5 years ago. MRI brain showed a lobulated lesion in the left frontal lobe. She came to our hospital for whole brain radiation as a diagnosed case of carcinoma of breast with brain metastasis. Review of MRI brain scan, revealed metastasis or query infective pathology. MR spectroscopy of the lesion revealed choline: creatinine and choline: NAA (N-Acety- laspartate) ratios of 1.6 and 1.5 respectively with the presence of lactate within the lesion suggestive of infective pathology. She underwent left fronto temporal craniotomy and evacuation of abscess and subdural empyema. Gram stain showed gram positive cocci. After 1 month of evacuation and treatment she was fine. This case suggested a note of caution in every case of a rapidly evolving space-occupying lesion independent of the patient’s previous history

  3. Diagnosis of brain death by transcranial Doppler sonography.

    Science.gov (United States)

    Bode, H; Sauer, M; Pringsheim, W

    1988-12-01

    The blood flow velocities in the basal cerebral arteries can be recorded at any age by transcranial Doppler sonography. We examined nine children with either initial or developing clinical signs of brain death. Soon after successful resuscitation increased diastolic flow velocities indicated a probable decrease in cerebrovascular resistance; this was of no particular prognostic importance. As soon as there was a clinical deterioration, there was a reduction in flow velocities with retrograde flow during early diastole, probably due to an increase in cerebrovascular resistance; this indicated a doubtful prognosis. In eight of the nine children with clinical signs of brain death a typical reverberating flow pattern was found, which was characterised by a counterbalancing short forward flow in systole and a short retrograde flow in early diastole. This indicated arrest of cerebral blood flow. One newborn showed normal systolic and end diastolic flow velocities in the basal cerebral arteries for two days despite clinical and electroencephalographic signs of brain death. Shunting of blood through the circle of Willis without effective cerebral perfusion may explain this phenomenon. No patient had the typical reverberating flow pattern without being clinically brain dead. Transcranial Doppler sonography is a reliable technique, which can be used at the bedside for the confirmation or the exclusion of brain death in children in addition to the clinical examination.

  4. A study of the application of Brain Atlas with and without +Gz acceleration conditions.

    Science.gov (United States)

    Li, Yifeng; Zhang, Lihui; Zhang, Tao; Li, Baohui

    2017-07-20

    The purposes of this study were to utilize Brain Atlas to investigate the fluctuations in the characteristics of human EEG, with and without +Gz acceleration produced by human centrifuge, and also to examine the G load endurance of human body. The Brain Atlas of the EEG signal with and without +Gz acceleration in a static state were compared in order to reveal the correlation and differences. When compared with those in a static state, it was found that for the EEG readings of the subjects undergoing +Gz acceleration conditions, the energy and gray scale values of the low-frequency component-delta rhythm showed significant increases, while the energy and gray scale values of the high-frequency component-beta rhythm showed significant decreases. Among these, the beta2 rhythm was determined to be significantly inhibited. These fluctuations suggested that the ischemia conditions of brain had been improved. Also, the recoveries in the energy and gray-scale values were determined to be faster, which suggested that the G load endurance of human body had been enhanced. The Brain Atlas was found to show observable changes in color. The experimental results indicated that the Brain Atlas was able to provide assistance during the exploration of the fluctuations in the characteristics of EEG, and provided a criterion to assist in the observations of the function state fluctuations of human brain with +Gz acceleration. It also assisted in the evaluations of the G load endurance of human body.

  5. Reduced Metabolism in Brain 'Control Networks' Following Cocaine-Cues Exposure in Female Cocaine Abusers

    International Nuclear Information System (INIS)

    Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Telang, F.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2011-01-01

    Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. To test this we compared brain metabolism (using PET and 18 FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video. Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6% ± 10) whereas males tended to increase it (+5.5% ± 18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus). Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from 'control networks' (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.

  6. 125I-iomazenil binding shows stress- and/or diazepam-induced reductions in mouse brain. Supporting data for 123I-iomazenil SPECT study of anxiety disorders

    International Nuclear Information System (INIS)

    Takahashi, Makoto; Odano, Ikuo; Fujita, Shozo; Ohkubo, Masaki.

    1997-01-01

    Effects of repeated swim stress on the binding of 125 I-iomazenil were examined in the brains of diazepam-treated and non-treated mice. The mice were orally administered diazepam or vehicle (0.5% ethylene glycol) and subjected to daily swim stress (at 20degC for 10 min) for seven consecutive days. The distribution and the amount of 125 I-iomazenil binding were analyzed autoradiographically after in vivo and in vitro binding experiments. Repeated swim stress decreased the in vivo binding in the hippocampus (p 125 I-iomazenil binding. These results suggest that we can investigate the pathophysiology of stress and anxiety with 123 I-iomazenil SPECT. Care must be taken concerning the effects of benzodiazepines. (author)

  7. [The blood-brain barrier in ageing persons].

    Science.gov (United States)

    Haaning, Nina; Damsgaard, Else Marie; Moos, Torben

    2018-03-26

    Brain capillary endothelial cells (BECs) form the ultra-tight blood-brain barrier (BBB). The permeability of the BBB increases with increasing age and neurovascular and neurodegenerative diseases. Major defects of the BBB can be initiated by increased permeability to plasma proteins in small arteriosclerotic arteries and release of proteins from degenerating neurons into the brain extracellular space. These proteins deposit in perivascular spaces, and subsequently negatively influence the BECs leading to decreased expression of barrier proteins. Detection of BBB defects by the use of non-invasive techniques is relevant for clinical use in settings with advanced age and severe brain disorders.

  8. Cloning, localization and differential expression of Neuropeptide-Y during early brain development and gonadal recrudescence in the catfish, Clarias gariepinus.

    Science.gov (United States)

    Sudhakumari, Cheni-Chery; Anitha, Arumugam; Murugananthkumar, Raju; Tiwari, Dinesh Kumar; Bhasker, Dharavath; Senthilkumaran, Balasubramanian; Dutta-Gupta, Aparna

    2017-09-15

    Neuropeptide-Y (NPY) has diverse physiological functions which are extensively studied in vertebrates. However, regulatory role of NPY in relation to brain ontogeny and recrudescence with reference to reproduction is less understood in fish. Present report for the first time evaluated the significance of NPY by transient esiRNA silencing and also analyzed its expression during brain development and gonadal recrudescence in the catfish, Clarias gariepinus. As a first step, full-length cDNA of NPY was cloned from adult catfish brain, which shared high homology with its counterparts from other teleosts upon phylogenetic analysis. Tissue distribution revealed dominant expression of NPY in brain and testis. NPY expression increased during brain development wherein the levels were higher in 100 and 150days post hatch females than the respective age-matched males. Seasonal cycle analysis showed high expression of NPY in brain during pre-spawning phase in comparison with other reproductive phases. Localization studies exhibited the presence of NPY, abundantly, in the regions of preoptic area, hypothalamus and pituitary. Transient silencing of NPY-esiRNA directly into the brain significantly decreased NPY expression in both the male and female brain of catfish which further resulted in significant decrease of transcripts of tryptophan hydroxylase 2, catfish gonadotropin-releasing hormone (cfGnRH), tyrosine hydroxylase and 3β-hydroxysteroid dehydrogenase in brain and luteinizing hormone-β/gonadotropin-II (lh-β/GTH-II) in pituitary exhibiting its influence on gonadal axis. In addition, significant decrease of several ovary-related transcripts was observed in NPY-esiRNA silenced female catfish, indicating the plausible role of NPY in ovary through cfGnRH-GTH axis. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Developmental Changes in Brain Network Hub Connectivity in Late Adolescence.

    Science.gov (United States)

    Baker, Simon T E; Lubman, Dan I; Yücel, Murat; Allen, Nicholas B; Whittle, Sarah; Fulcher, Ben D; Zalesky, Andrew; Fornito, Alex

    2015-06-17

    The human brain undergoes substantial development throughout adolescence and into early adulthood. This maturational process is thought to include the refinement of connectivity between putative connectivity hub regions of the brain, which collectively form a dense core that enhances the functional integration of anatomically distributed, and functionally specialized, neural systems. Here, we used longitudinal diffusion magnetic resonance imaging to characterize changes in connectivity between 80 cortical and subcortical anatomical regions over a 2 year period in 31 adolescents between the ages of 15 and 19 years. Connectome-wide analysis indicated that only a small subset of connections showed evidence of statistically significant developmental change over the study period, with 8% and 6% of connections demonstrating decreased and increased structural connectivity, respectively. Nonetheless, these connections linked 93% and 90% of the 80 regions, respectively, pointing to a selective, yet anatomically distributed pattern of developmental changes that involves most of the brain. Hub regions showed a distinct tendency to be highly connected to each other, indicating robust "rich-club" organization. Moreover, connectivity between hubs was disproportionately influenced by development, such that connectivity between subcortical hubs decreased over time, whereas frontal-subcortical and frontal-parietal hub-hub connectivity increased over time. These findings suggest that late adolescence is characterized by selective, yet significant remodeling of hub-hub connectivity, with the topological organization of hubs shifting emphasis from subcortical hubs in favor of an increasingly prominent role for frontal hub regions. Copyright © 2015 the authors 0270-6474/15/359078-10$15.00/0.

  10. Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice.

    Directory of Open Access Journals (Sweden)

    Caitlin S Latimer

    Full Text Available Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging.

  11. Quantitative autoradiography of [3H]ouabain binding sites in rat brain

    International Nuclear Information System (INIS)

    Spyropoulos, A.C.; Rainbow, T.C.

    1984-01-01

    In vitro quantitative autoradiography was used to localize in rat brain binding sites for [ 3 H]ouabain, an inhibitor of the Na + ,K + -ATPase. High levels of [ 3 H]ouabain sites were found in the superior and inferior colliculi, the mammillary nucleus, the interpeduncular nucleus, and in various divisions of the olfactory, auditory and somatomotor systems. The heterogeneous distribution of [ 3 H]ouabain binding closely parallels the regional brain glucose consumption as determined by the [ 14 C]deoxyglucose method. Lesion studies of the rat hippocampus using the excitotoxin, ibotenic acid, showed both a marked decrease of neuronal cell types on the injected side and a corresponding decrease in [ 3 H]ouabain binding, indicating that some of the [ 3 H]ouabain binding sites are localized to neurons. The close correlation between [ 3 H]ouabain binding and regional glucose utilization provides further evidence for a linkage between glucose utilization and the neuronal Na + ,K + -ATPase. (Auth.)

  12. Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.

    Science.gov (United States)

    Eylers, V V; Maudsley, A A; Bronzlik, P; Dellani, P R; Lanfermann, H; Ding, X-Q

    2016-03-01

    Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain (1)H-MRS was used in combination with quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure. Sixty healthy volunteers, 21-70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2' were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data. Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2' decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2' in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2' in the putamen. The effects of normal aging on brain metabolites and microstructure are region-dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients. © 2016 by American Journal of Neuroradiology.

  13. Dysfunctional whole brain networks in mild cognitive impairment patients: an fMRI study

    Science.gov (United States)

    Liu, Zhenyu; Bai, Lijun; Dai, Ruwei; Zhong, Chongguang; Xue, Ting; You, Youbo; Tian, Jie

    2012-03-01

    Mild cognitive impairment (MCI) was recognized as the prodromal stage of Alzheimer's disease (AD). Recent researches have shown that cognitive and memory decline in AD patients is coupled with losses of small-world attributes. However, few studies pay attention to the characteristics of the whole brain networks in MCI patients. In the present study, we investigated the topological properties of the whole brain networks utilizing graph theoretical approaches in 16 MCI patients, compared with 18 age-matched healthy subjects as a control. Both MCI patients and normal controls showed small-world architectures, with large clustering coefficients and short characteristic path lengths. We detected significantly longer characteristic path length in MCI patients compared with normal controls at the low sparsity. The longer characteristic path lengths in MCI indicated disrupted information processing among distant brain regions. Compared with normal controls, MCI patients showed decreased nodal centrality in the brain areas of the angular gyrus, heschl gyrus, hippocampus and superior parietal gyrus, while increased nodal centrality in the calcarine, inferior occipital gyrus and superior frontal gyrus. These changes in nodal centrality suggested a widespread rewiring in MCI patients, which may be an integrated reflection of reorganization of the brain networks accompanied with the cognitive decline. Our findings may be helpful for further understanding the pathological mechanisms of MCI.

  14. Altered brain structural connectivity in post-traumatic stress disorder: a diffusion tensor imaging tractography study.

    Science.gov (United States)

    Long, Zhiliang; Duan, Xujun; Xie, Bing; Du, Handan; Li, Rong; Xu, Qiang; Wei, Luqing; Zhang, Shao-xiang; Wu, Yi; Gao, Qing; Chen, Huafu

    2013-09-25

    Post-traumatic stress disorder (PTSD) is characterized by dysfunction of several discrete brain regions such as medial prefrontal gyrus with hypoactivation and amygdala with hyperactivation. However, alterations of large-scale whole brain topological organization of structural networks remain unclear. Seventeen patients with PTSD in motor vehicle accident survivors and 15 normal controls were enrolled in our study. Large-scale structural connectivity network (SCN) was constructed using diffusion tensor tractography, followed by thresholding the mean factional anisotropy matrix of 90 brain regions. Graph theory analysis was then employed to investigate their aberrant topological properties. Both patient and control group showed small-world topology in their SCNs. However, patients with PTSD exhibited abnormal global properties characterized by significantly decreased characteristic shortest path length and normalized characteristic shortest path length. Furthermore, the patient group showed enhanced nodal centralities predominately in salience network including bilateral anterior cingulate and pallidum, and hippocampus/parahippocamus gyrus, and decreased nodal centralities mainly in medial orbital part of superior frontal gyrus. The main limitation of this study is the small sample of PTSD patients, which may lead to decrease the statistic power. Consequently, this study should be considered an exploratory analysis. These results are consistent with the notion that PTSD can be understood by investigating the dysfunction of large-scale, spatially distributed neural networks, and also provide structural evidences for further exploration of neurocircuitry models in PTSD. © 2013 Elsevier B.V. All rights reserved.

  15. Predicting individual brain maturity using dynamic functional connectivity

    Directory of Open Access Journals (Sweden)

    Jian eQin

    2015-07-01

    Full Text Available Neuroimaging-based functional connectivity (FC analyses have revealed significant developmental trends in specific intrinsic connectivity networks linked to cognitive and behavioral maturation. However, knowledge of how brain functional maturation is associated with FC dynamics at rest is limited. Here, we examined age-related differences in the temporal variability of FC dynamics with data publicly released by the Nathan Kline Institute (NKI (n=183, ages 7-30 and showed that dynamic inter-region interactions can be used to accurately predict individual brain maturity across development. Furthermore, we identified a significant age-dependent trend underlying dynamic inter-network FC, including increasing variability of the connections between the visual network, default mode network (DMN and cerebellum as well as within the cerebellum and DMN and decreasing variability within the cerebellum and between the cerebellum and DMN as well as the cingulo-opercular network. Overall, the results suggested significant developmental changes in dynamic inter-network interaction, which may shed new light on the functional organization of typical developmental brains.

  16. Assessment of drug disposition in the perfused rat brain by statistical moment analysis

    International Nuclear Information System (INIS)

    Sakane, T.; Nakatsu, M.; Yamamoto, A.; Hashida, M.; Sezaki, H.; Yamashita, S.; Nadai, T.

    1991-01-01

    Drug disposition in the brain was investigated by statistical moment analysis using an improved in situ brain perfusion technique. The right cerebral hemisphere of the rat was perfused in situ. The drug and inulin were injected into the right internal carotid artery as a rapid bolus and the venous outflow curve at the posterior facial vein was obtained. The infusion rate was adjusted to minimize the flow of perfusion fluid into the left hemisphere. The obtained disposition parameters were characteristics and considered to reflect the physicochemical properties of each drug. Antipyrine showed a small degree of initial uptake. Therefore, its apparent distribution volume (Vi) and apparent intrinsic clearance (CLint,i) were small. Diazepam showed large degrees of both influx and efflux and, thus, a large Vi. Water showed parameters intermediate between those of antipyrine and those of diazepam. Imipramine, desipramine, and propranolol showed a large CLint,i compared with those of the other drugs. The extraction ratio of propranolol significantly decreased with increasing concentrations of unlabeled propranolol in the perfusion fluid. These findings may be explained partly by the tissue binding of these drugs. In conclusion, the present method is useful for studying drug disposition in the brain

  17. Brain fat embolism

    International Nuclear Information System (INIS)

    Sugiura, Yoshihiro; Kawamura, Yasutaka; Suzuki, Hisato; Yanagimoto, Masahiro; Goto, Yukio

    1994-01-01

    Recently CT and MR imaging have demonstrated that cerebral edema is present in cases of fat embolism syndrome. To simulate this we have made a model of brain-fat embolism in rats under MR imaging. In 20 rats, we did intravenous injection of heparinized blood, 1.5 ml·kg -1 taken from femoral bone marrow cavity. Twenty four hours after the injection, we examined the MR images (1.5 tesla, spin-echo method) of brains and histologic findings of brains and lungs were obtained. In 5 of 20 rats, high signal intensity on T2-weighted images and low signal intensity on T1-weighted images were observed in the area of the unilateral cerebral cortex or hippocampus. These findings showed edema of the brains. They disappeared, however, one week later. Histologic examinations showed massive micro-fat emboli in capillaries of the deep cerebral cortex and substantia nigra, but no edematous findings of the brain were revealed in HE staining. In pulmonary arteries, we also found large fat emboli. We conclude that our model is a useful one for the study of brain fat embolism. (author)

  18. Corvitin restores metallothionein and glial fibrillary acidic protein levels in rat brain affected by pituitrin-izadrin

    OpenAIRE

    H. N. Shiyntum; O. O. Dovban; Y. P. Kovalchuk; T. Ya. Yaroshenko2; G. A. Ushakova1

    2017-01-01

    In this research, we investigated the effect of pituitrin-izadrin induced injury on the levels of metallothionein (MT) and soluble and filament forms of glial fibrillary acidic protein (GFAP) in the hippocampus, cerebellum, thalamus, and the cerebral cortex, and examined the effect of corvitin on the brain under the noted changes. Our results showed oppositely directed changes – a decrease in the level of MT and an increase in GFAP in the rat brain, with a tendency to astrogliosis development...

  19. Decreasing-Rate Pruning Optimizes the Construction of Efficient and Robust Distributed Networks.

    Directory of Open Access Journals (Sweden)

    Saket Navlakha

    2015-07-01

    Full Text Available Robust, efficient, and low-cost networks are advantageous in both biological and engineered systems. During neural network development in the brain, synapses are massively over-produced and then pruned-back over time. This strategy is not commonly used when designing engineered networks, since adding connections that will soon be removed is considered wasteful. Here, we show that for large distributed routing networks, network function is markedly enhanced by hyper-connectivity followed by aggressive pruning and that the global rate of pruning, a developmental parameter not previously studied by experimentalists, plays a critical role in optimizing network structure. We first used high-throughput image analysis techniques to quantify the rate of pruning in the mammalian neocortex across a broad developmental time window and found that the rate is decreasing over time. Based on these results, we analyzed a model of computational routing networks and show using both theoretical analysis and simulations that decreasing rates lead to more robust and efficient networks compared to other rates. We also present an application of this strategy to improve the distributed design of airline networks. Thus, inspiration from neural network formation suggests effective ways to design distributed networks across several domains.

  20. Brain endothelial dysfunction in cerebral adrenoleukodystrophy.

    Science.gov (United States)

    Musolino, Patricia L; Gong, Yi; Snyder, Juliet M T; Jimenez, Sandra; Lok, Josephine; Lo, Eng H; Moser, Ann B; Grabowski, Eric F; Frosch, Matthew P; Eichler, Florian S

    2015-11-01

    See Aubourg (doi:10.1093/awv271) for a scientific commentary on this article.X-linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids. Its most severe neurological manifestation is cerebral adrenoleukodystrophy. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood-brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules. ABCD1, but not its closest homologue ABCD2, is highly expressed in human brain microvascular endothelial cells, far exceeding its expression in the systemic vasculature. Silencing of ABCD1 in human brain microvascular endothelial cells causes accumulation of very long chain fatty acids, but much later than the immediate upregulation of adhesion molecules and decrease in tight junction proteins. This results in greater adhesion and transmigration of monocytes across the endothelium. PCR-array screening of human brain microvascular endothelial cells after ABCD1 silencing revealed downregulation of both mRNA and protein levels of the transcription factor c-MYC (encoded by MYC). Interestingly, MYC silencing mimicked the effects of ABCD1 silencing on CLDN5 and ICAM1 without decreasing the levels of ABCD1 protein itself. Together, these data demonstrate that ABCD1 deficiency induces significant alterations in brain endothelium via c-MYC and may thereby contribute to the increased trafficking of leucocytes across the blood-brain barrier as seen in cerebral adrenouleukodystrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Brain hypoperfusion on Tc-99m-ethylene dicysteine diethyl ester single-photon emission computed tomography in Hashimoto's encephalopathy

    International Nuclear Information System (INIS)

    Grande, María Luz Domínguez; Rayo, Juan Ignacio; Serrano, Justo; Infante, Jose Rafael; Garcia, Lucia; Duran, Carmen; Constantino, Ana

    2013-01-01

    We present a 17-year-old female, previously diagnosed of autoimmune hyperthyroidism who had an acute neurological episode and presented high antithyroid antibodies titers, cerebral spinal fluid and electroencephalogram changes. 99m Tc ethylene dicysteine diethyl ester brain single-photon emission computed tomography (SPECT) showed global and patchy hypoperfusion. With glucocorticoid therapy, clinical symptoms disappeared; there was a decrease in antithyroid antibody levels and repeat brain SPECT revealed improvement of perfusion. (author)

  2. Distribution of the insecticide 14 C-fen valerate and its effect on protein and amino acid content in different brain areas of the rat

    International Nuclear Information System (INIS)

    Aly, M.A.S.

    1998-01-01

    Intragastric administration of fenvalerate (45 mg/kg) to male rats induced symptoms associated with gamma-cyano pyrethroids (type II syndrome). Fenvalerate crossed blood brain barrier and reached different brain areas. The highest concentration of fenvalerate was found in striatum (18.7+2.5 Mou/g) followed by pons + medulla oblongata (10.4+ 0.91Moug/g) after 24 h of the insecticide administration. A decrease in the protein content in different brain areas was recorded at 24 h. However, it was observed that there was a tendency for the protein level to recover at 48 h although it was still lower than corresponding controlgroup. Excitatory neurotransmitter amino acids, glutamic and aspartic, in the pons + medulla oblongata showed a prominent decrease (-9.9 and 7.0%, respectively). Inhibitory neurotransmitter amino acids, glycine and alanine, showed a slight decrease. On the other hand, the amino acids in the striatum revealed fluctuating changes. Amino acids acting as a precursor of neurotransmitter were also affected in the selected brain areas. The data obtained revealed that fenvalerate caused subtle disruption in the integrity of the CNS and there is a possibility that such disruption might result in physiological and behavioural alteration which may affect the organism ability to interact with environment

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

    Science.gov (United States)

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

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

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

    Science.gov (United States)

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

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

  5. Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently.

    Science.gov (United States)

    Lau, Christine Li Ling; Chan, Sook Tyng; Selvaratanam, Manimegahlai; Khoo, Hui Wen; Lim, Adeline Yi Ling; Modamio, Pilar; Mariño, Eduardo L; Segarra, Ignacio

    2015-08-01

    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P brain (P male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P brain, liver, and kidney (all P male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P female mice and in kidney (male and female mice) but decreased 55% in brain (P differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  6. Depressed patients have decreased binding of tritiated imipramine to platelet serotonin ''transporter''

    International Nuclear Information System (INIS)

    Paul, S.M.; Rehavi, M.; Skolnick, P.; Ballenger, J.C.; Goodwin, F.K.

    1981-01-01

    The high-affinity tritiated (3H) imipramine binding sites are functionally (and perhaps structurally) associated with the presynaptic neuronal and platelet uptake sites for serotonin. Since there is an excellent correlation between the relative potencies of a series of antidepressants in displacing 3H-imipramine from binding sites in human brain and platelet, we have examined the binding of 3H-imipramine to platelets from 14 depressed patients and 28 age- and sex-matched controls. A highly significant decrease in the number of 3H-imipramine binding sites, with no significant change in the apparent affinity constants, was observed in platelets from the depressed patients compared with the controls. These results, coupled with previous studies showing a significant decrease in the maximal uptake of serotonin in platelets from depressed patients, suggest that an inherited or acquired deficiency of the serotonin transport protein or proteins may be involved in the pathogenesis of depression

  7. Cannabis Essential Oil: A Preliminary Study for the Evaluation of the Brain Effects

    Directory of Open Access Journals (Sweden)

    Nadia Gulluni

    2018-01-01

    Full Text Available We examined the effects of essential oil from legal (THC <0.2% w/v hemp variety on the nervous system in 5 healthy volunteers. GC/EIMS and GC/FID analysis of the EO showed that the main components were myrcene and β-caryophyllene. The experiment consisted of measuring autonomic nervous system (ANS parameters; evaluations of the mood state; and electroencephalography (EEG recording before treatment, during treatment, and after hemp inhalation periods as compared with control conditions. The results revealed decreased diastolic blood pressure, increased heart rate, and significant increased skin temperature. The subjects described themselves as more energetic, relaxed, and calm. The analysis EEG showed a significant increase in the mean frequency of alpha (8–13 Hz and significant decreased mean frequency and relative power of beta 2 (18,5–30 Hz waves. Moreover, an increased power, relative power, and amplitude of theta (4–8 Hz and alpha brain waves activities and an increment in the delta wave (0,5–4 Hz power and relative power was recorded in the posterior region of the brain. These results suggest that the brain wave activity and ANS are affected by the inhalation of the EO of Cannabis sativa suggesting a neuromodular activity in cases of stress, depression, and anxiety.

  8. Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake

    NARCIS (Netherlands)

    Mars, M.; Graaf, de C.; Groot, de C.P.G.M.; Kok, F.J.

    2005-01-01

    The decrease in leptin after energy restriction is a starvation signal to the brain. Several studies have found an association between this decrease and subjective appetite; however, no solid data are available on the acute decrease in fasting leptin concentration and subsequent caloric

  9. Adolescent heavy drinkers' amplified brain responses to alcohol cues decrease over one month of abstinence.

    Science.gov (United States)

    Brumback, Ty; Squeglia, Lindsay M; Jacobus, Joanna; Pulido, Carmen; Tapert, Susan F; Brown, Sandra A

    2015-07-01

    Heavy drinking during adolescence is associated with increased reactivity to alcohol related stimuli and to differential neural development. Alcohol cue reactivity has been widely studied among adults with alcohol use disorders, but little is known about the neural substrates of cue reactivity in adolescent drinkers. The current study aimed to identify changes in blood-oxygen level dependent (BOLD) signal during a cue reactivity task pre- and post-monitored abstinence from alcohol. Demographically matched adolescents (16.0-18.9 years, 54% female) with histories of heavy episodic drinking (HD; n=22) and light or non-drinking control teens (CON; n=16) were recruited to participate in a month-long study. All participants completed a functional Magnetic Resonance Imaging (fMRI) scan with an alcohol cue reactivity task and substance use assessments at baseline and after 28 days of monitored abstinence from alcohol and drugs (i.e., urine toxicology testing every 48-72 h). Repeated-measure analysis of variance (ANOVA) examined main effects of group, time, and group×time interactions on BOLD signal response in regions of interest defined by functional differences at baseline. The HD group exhibited greater (pbrain regions, differences in BOLD response were no longer apparent following a month of abstinence, suggesting a decrease in alcohol cue reactivity among adolescent non-dependent heavy drinkers as a consequence of abstaining from alcohol. These results highlight the malleability of adolescent brain function despite no formal intervention targeting cue reactivity. Increased understanding of the neural underpinnings of cue reactivity could have implications for prevention and intervention strategies in adolescent heavy alcohol users. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

    Science.gov (United States)

    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  11. Clinical study on brain tumors in the aged

    International Nuclear Information System (INIS)

    Teramoto, Akira; Manaka, Shinya; Takakura, Kintomo

    1981-01-01

    In order to investigate the clinical features and the prognosis of brain tumors in the aged, 132 cases over 60 years of age were studied from the consecutive series of 1,793 brain tumors in the University of Tokyo Hospital (1963 - 1979). The incidence of brain tumors in the aged was 7.4% on the whole, while it showed a significant increase from 4.8% (1960's) to 11.5% (the later half of 1970's). Histologically, meningiomas were the most common tumors (26%), followed by neurinomas (17%), pituitary adenomas (16%) and metastatic tumors (15%). Malignant gliomas were found more frequently than benign ones. There were more meningiomas as age advanced. The proportion and the number of meningioma cases has obviously increased in recent years when CT scanners became available. Symptoms of intracranial hypertention were found less frequently in aged patients although they were still common in cases of glioblastomas. The duration from onset to surgery was relatively long, especially in cases of neurinomas and pituitary adenomas. Two cases of astrocytomas belonged to the category of silent gliomas. Overall operative mortality rate was 10.6%, while it showed a marked decrease to 4.7% in the 1970's. Five-year survival rates were as follows: meningiomas (58%), pituitary adenomas (70%), neurinomas (80%), glioblastomas (20%) and astrocytomas (25%). As for functional prognoses, 30% of the patients showed poor states on ADL, mostly because of residual psychic disorders. (author)

  12. Monoamine oxidase A (MAO A) inhibitors decrease glioma progression

    Science.gov (United States)

    Vaikari, Vijaya Pooja; Kota, Rajesh; Chen, Kevin; Yeh, Tzu-Shao; Jhaveri, Niyati; Groshen, Susan L.; Olenyuk, Bogdan Z.; Chen, Thomas C.; Hofman, Florence M.; Shih, Jean C.

    2016-01-01

    Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI-148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-alone drugs or as combination therapy with low dose TMZ for drug-resistant gliomas. NMI can also be used as a non-invasive imaging tool. Thus has a dual function for both therapy and diagnosis. PMID:26871599

  13. Differences in MRI findings in cases showing ring-enhancement on a CT scan

    International Nuclear Information System (INIS)

    Tokiwa, Kaichi; Hashimoto, Takashi; Miyasaka, Yoshio; Yada, Kenzoh; Kan, Shinichi; Takagi, Hiroshi.

    1990-01-01

    It is sometimes difficult to differentiate between a brain abscess and a tumor, for both show ring-enhancement on a CT scan. The present authors have studied the benefit of MRI for the differential diagnosis of these two lesions. The subjects of this study were 6 cases of brain abscess and 10 cases of brain tumor, all of them showing ring-enhancement on a CT scan. The MRI findings were compared with those of the CT scan taken at almost the same time, especially focussing on the difference in the ring-enhancement. In 5 out of the 6 cases of brain abscess, T 2 -weighted MRI demonstrated a comparatively thin and homogeneous low-intensity, round rim. In the cases of brain tumor, however, none of the cases demonstrated this typical low-intensity, round rim; rather, in them the rim was thick and irregular. The authors can conclude that those MRI findings can serve as important differential diagnostic findings between brain abscess and tumor; also, MRI may be used as a landmark for terminating the administration of antibiotics in cases of brain abscess. (author)

  14. Study on developing brain damage of neonatal rats induced by enriched uranium

    International Nuclear Information System (INIS)

    Gu Guixiong; Zhu Shoupeng; Yang Shuqin

    2000-01-01

    Objective: The injurious effects of enriched uranium 235 U on developing brain of neonatal Wistar pure bred rats were studied. Methods: The model of irradiation induced brain damage in vivo was settled. The effects of cerebrum exposure by 235 U on somatic growth and neuro-behavior development of neonatal rats were examined by thirteen index determination of multiple parameters. The dynamic retention of autoradiographic tracks of 235 U in cells of developing brain was observed. The changes of NSE, IL-1β, SOD, and ET in cerebral cortex, hippocampus, diencephalon, cerebellum after expose to 235 U were examined with radioimmunoassay. Results: The somatic growth such as increase of body weight and brain weight was lower significantly. The retardation of development was found such as eye opening, sensuous function as auditory startle, movement and coordination function and activity as swimming, physiological reflexes as negative geotaxis, surface righting, grasping reflex suspension and the tendency behavior. The data showed delayed growth and abnormal neuro-behavior. The micro-autoradiographic tracing showed that the tracks of 235 U were mainly accumulated in the nucleus of developing brain. At the same time only few tracks appeared in the cytoplasm and interval between cells. Experimental study showed that when the dose of 235 U irradiation was increased, the level of NSE was decreased and the IL-1β was increased. However, the results indicated that SOD and ET can be elevated by the low dose irradiation of 235 U, and can be inhibited by the high dose. Conclusion: The behavior of internal irradiation from 235 U on the developing brain damage of neonatal rats were of sensibility and compensation in nervous cells

  15. Correlation between brain circuit segregation and obesity.

    Science.gov (United States)

    Chao, Seh-Huang; Liao, Yin-To; Chen, Vincent Chin-Hung; Li, Cheng-Jui; McIntyre, Roger S; Lee, Yena; Weng, Jun-Cheng

    2018-01-30

    Obesity is a major public health problem. Herein, we aim to identify the correlation between brain circuit segregation and obesity using multimodal functional magnetic resonance imaging (fMRI) techniques and analysis. Twenty obese patients (BMI=37.66±5.07) and 30 healthy controls (BMI=22.64±3.45) were compared using neuroimaging and assessed for symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). All participants underwent resting-state fMRI (rs-fMRI) and T1-weighted imaging using a 1.5T MRI. Multimodal MRI techniques and analyses were used to assess obese patients, including the functional connectivity (FC), amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), graph theoretical analysis (GTA), and voxel-based morphometry (VBM). Correlations between brain circuit segregation and obesity were also calculated. In the VBM, obese patients showed altered gray matter volumes in the amygdala, thalamus and putamen. In the FC, the obesity group showed increased functional connectivity in the bilateral anterior cingulate cortex and decreased functional connectivity in the frontal gyrus of default mode network. The obesity group also exhibited altered ALFF and ReHo in the prefrontal cortex and precuneus. In the GTA, the obese patients showed a significant decrease in local segregation and a significant increase in global integration, suggesting a shift toward randomization in their functional networks. Our results may provide additional evidence for potential structural and functional imaging markers for clinical diagnosis and future research, and they may improve our understanding of the underlying pathophysiology of obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophin factor- and parvalbumin-positive neurons than males.

    Science.gov (United States)

    Ravenelle, Rebecca; Berman, Ariel K; La, Jeffrey; Mason, Briana; Asumadu, Evans; Yelleswarapu, Chandra; Donaldson, S Tiffany

    2018-04-01

    In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like behavior and response to the prototypical anti-anxiety drug, diazepam. We used 6th generation outbred lines of adult Long Evans rats with high and low anxiety-like behavior phenotypes to investigate the impact of proestrus on the baseline and diazepam-induced behavior. At three doses of diazepam (0, 0.1, and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus maze of adult male and female rats. We assessed parvalbumin and brain-derived neurotrophin protein levels in forebrain and limbic structures implicated in anxiety/stress using immunohistochemistry. At baseline, we saw significant differences between anxiety lines, with high anxiety lines displaying less time on the open arms of the elevated plus maze, and less open arm entries, regardless of sex. During proestrus, high anxiety females showed less anxiety-like behavior at 0.1 mg/kg, while low anxiety females displayed less anxiety-like behavior at 0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was elevated in females in the medial prefrontal cortex and central amygdala, while parvalbumin-immunoreactive cells were greater in males in the medial prefrontal cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and dentate gyrus relative to males from the same line. In sum, when tested in proestrus, females showed greater anxiolytic effects of diazepam relative to males, and this correlated with increases in neurotrophin and parvalbumin neuron density in corticolimbic structures. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. Characteristics of Brain Perfusion in Patients of Parkinson's Disease

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young Jin; Park, Min Jung; Kim, Jae Woo; Kang, Young Kang [Dong-A University College of Medicine, Busan (Korea, Republic of)

    2008-02-15

    It was well known that cerebral blood perfusion is normal or diffusely decreased in the majority of patients with Parkinson's disease (PD). Actually we interpreted brain perfusion SPECT images of PD patients in the clinical situation, we observed various cerebral perfusion patterns in patients with PD. So we performed brain perfusion SPECT to know the brain perfusion patterns of PD patients and the difference of perfusion patterns according to the sex and the age. Also we classified PD patients into small groups based on the brain perfusion pattern. Two hundred nineteen patients (M: 70, F: 149, mean age: 62.9{+-}6.9 y/o) who were diagnosed as PD without dementia clinically and 55 patients (M: 15, F: 40, mean age: 61.4{+-}9.2 y/o) as normal controls who had no past illness history were performed {sup 99m}Tc-HMPAO brain perfusion SPECT and neuropsychological test. At first, we compared all patients with PD and normal controls. Brain perfusion in left inferior frontal gyrus, left insula, left transverse temporal gyrus, left inferior parietal lobule, left superior parietal lobule, right precuneus, right caudate tail were lower in patients with PD than normal controls. Secondly, we compared male and female patients with PD and normal controls, respectively. Brain perfusion SPECT showed more decreased cerebral perfusion in left hemisphere than right side in both male and female patients compared to normal controls. And there was larger hypoperfusion area in female patients compared with male. Thirdly, we classified patients with PD and normal controls into 4 groups according to the age and compared brain perfusion respectively. In patient below fifties, brain perfusion in both occipitoparietal and left temporal lobe were lower in PD group. As the patients with PD grew older, hypoperfusion area were shown in both frontal, temporal and limbic lobes. Fourthly, We were able to divide patients into small groups based on cerebral perfusion pattern. There was normal

  18. Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain.

    Science.gov (United States)

    Schnydrig, Sabine; Korner, Lukas; Landweer, Svenja; Ernst, Beat; Walker, Gaby; Otten, Uwe; Kunz, Dieter

    2007-12-11

    Peripheral inflammation induced by intraperitoneal (i.p.) injection of Lipopolysaccharide (LPS) is known to cause functional impairments in the brain affecting memory and learning. One of mechanisms may be the interference with neurotrophin (NT) expression and function. In the current study we administered a single, high dose of LPS (3mg/kg, i.p.) into mice and investigated changes in brain-derived neurotrophic factor (BDNF) gene expression within 1-6 days after LPS injection. Crude synaptosomes were isolated from brain tissue and subjected to Western-blot analyses. We found transient reductions in synaptosomal proBDNF- and BDNF protein expression, with a maximal decrease at day 3 as compared to saline injected controls. The time course of reduction of BDNF mRNA in whole brain extracts parallels the decrease in protein levels in synaptosomes. LPS effects in the central nervous system (CNS) are known to crucially involve the activation of the hypothalamic-pituitary-adrenal (HPA) axis. We analysed the time course of corticotropin releasing hormone (CRH)- and proopiomelanocortin (POMC) mRNA expression. As observed for BDNF-, CRH- and POMC mRNA levels are also significantly reduced on day 3 indicating a comparable time course. These results suggest that peripheral inflammation causes a reduction of trophic supply in the brain, including BDNF at synaptic sites. The mechanisms involved could be a negative feedback of the activated HPA axis.

  19. Potent and Selective BACE-1 Peptide Inhibitors Lower Brain Aβ Levels Mediated by Brain Shuttle Transport

    Directory of Open Access Journals (Sweden)

    Nadine Ruderisch

    2017-10-01

    Full Text Available Therapeutic approaches to fight Alzheimer's disease include anti-Amyloidβ (Aβ antibodies and secretase inhibitors. However, the blood-brain barrier (BBB limits the brain exposure of biologics and the chemical space for small molecules to be BBB permeable. The Brain Shuttle (BS technology is capable of shuttling large molecules into the brain. This allows for new types of therapeutic modalities engineered for optimal efficacy on the molecular target in the brain independent of brain penetrating properties. To this end, we designed BACE1 peptide inhibitors with varying lipid modifications with single-digit picomolar cellular potency. Secondly, we generated active-exosite peptides with structurally confirmed dual binding mode and improved potency. When fused to the BS via sortase coupling, these BACE1 inhibitors significantly reduced brain Aβ levels in mice after intravenous administration. In plasma, both BS and non-BS BACE1 inhibitor peptides induced a significant time- and dose-dependent decrease of Aβ. Our results demonstrate that the BS is essential for BACE1 peptide inhibitors to be efficacious in the brain and active-exosite design of BACE1 peptide inhibitors together with lipid modification may be of therapeutic relevance.

  20. [Research of anti-aging mechanism of ginsenoside Rg1 on brain].

    Science.gov (United States)

    Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

    2014-11-01

    Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus

  1. Progesterone treatment shows benefit in a pediatric model of moderate to severe bilateral brain injury.

    Directory of Open Access Journals (Sweden)

    Rastafa I Geddes

    Full Text Available Controlled cortical impact (CCI models in adult and aged Sprague-Dawley (SD rats have been used extensively to study medial prefrontal cortex (mPFC injury and the effects of post-injury progesterone treatment, but the hormone's effects after traumatic brain injury (TBI in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury.Twenty-eight-day old (PND 28 male Sprague Dawley rats received sham (n = 24 or CCI (n = 47 injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight or vehicle injections on post-injury days (PID 1-7, subjected to behavioral testing from PID 9-27, and analyzed for lesion size at PID 28.The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats.Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits.

  2. In vivo electrical conductivity imaging of a canine brain using a 3 T MREIT system

    International Nuclear Information System (INIS)

    Kim, Hyung Joong; Oh, Tong In; Kim, Young Tae; Lee, Byung Il; Woo, Eung Je; Lee, Soo Yeol; Seo, Jin Keun; Kwon, Ohin; Park, Chunjae; Kang, Byeong Teck; Park, Hee Myung

    2008-01-01

    Magnetic resonance electrical impedance tomography (MREIT) aims at producing high-resolution cross-sectional conductivity images of an electrically conducting object such as the human body. Following numerous phantom imaging experiments, the most recent study demonstrated successful conductivity image reconstructions of postmortem canine brains using a 3 T MREIT system with 40 mA imaging currents. Here, we report the results of in vivo animal imaging experiments using 5 mA imaging currents. To investigate any change of electrical conductivity due to brain ischemia, canine brains having a regional ischemic model were scanned along with separate scans of canine brains having no disease model. Reconstructed multi-slice conductivity images of in vivo canine brains with a pixel size of 1.4 mm showed a clear contrast between white and gray matter and also between normal and ischemic regions. We found that the conductivity value of an ischemic region decreased by about 10–14%. In a postmortem brain, conductivity values of white and gray matter decreased by about 4–8% compared to those in a live brain. Accumulating more experience of in vivo animal imaging experiments, we plan to move to human experiments. One of the important goals of our future work is the reduction of the imaging current to a level that a human subject can tolerate. The ability to acquire high-resolution conductivity images will find numerous clinical applications not supported by other medical imaging modalities. Potential applications in biology, chemistry and material science are also expected

  3. Metabolite concentrations in the developing brain estimated with proton MR spectroscopy

    DEFF Research Database (Denmark)

    Toft, P B; Leth, H; Lou, H C

    1995-01-01

    (stimulated-echo acquisition mode) sequences with different TEs and TRs. Water was used as an internal standard. The T1 of choline-containing compounds (Cho) and the T1 of phosphocreatine plus creatine (PCr+Cr) decreased. The T2 of the N-acetyl-L-aspartate (NAA) resonance increased, probably because...... of a relatively larger signal overlap with glutamate in the most immature brains. The concentration of NAA almost doubled, whereas the Cho concentration showed only a nonsignificant tendency to decrease; therefore, the well-known increase in the ratio of NAA to Cho appears to be due mostly to an increase in NAA...

  4. Evolution of brain region volumes during artificial selection for relative brain size.

    Science.gov (United States)

    Kotrschal, Alexander; Zeng, Hong-Li; van der Bijl, Wouter; Öhman-Mägi, Caroline; Kotrschal, Kurt; Pelckmans, Kristiaan; Kolm, Niclas

    2017-12-01

    The vertebrate brain shows an extremely conserved layout across taxa. Still, the relative sizes of separate brain regions vary markedly between species. One interesting pattern is that larger brains seem associated with increased relative sizes only of certain brain regions, for instance telencephalon and cerebellum. Till now, the evolutionary association between separate brain regions and overall brain size is based on comparative evidence and remains experimentally untested. Here, we test the evolutionary response of brain regions to directional selection on brain size in guppies (Poecilia reticulata) selected for large and small relative brain size. In these animals, artificial selection led to a fast response in relative brain size, while body size remained unchanged. We use microcomputer tomography to investigate how the volumes of 11 main brain regions respond to selection for larger versus smaller brains. We found no differences in relative brain region volumes between large- and small-brained animals and only minor sex-specific variation. Also, selection did not change allometric scaling between brain and brain region sizes. Our results suggest that brain regions respond similarly to strong directional selection on relative brain size, which indicates that brain anatomy variation in contemporary species most likely stem from direct selection on key regions. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  5. Impact of bronchopulmonary dysplasia on brain and retina

    Directory of Open Access Journals (Sweden)

    Annie Wing Hoi Poon

    2016-04-01

    Full Text Available Many premature newborns develop bronchopulmonary dysplasia (BPD, a chronic lung disease resulting from prolonged mechanical ventilation and hyperoxia. BPD survivors typically suffer long-term injuries not only to the lungs, but also to the brain and retina. However, currently it is not clear whether the brain and retinal injuries in these newborns are related only to their prematurity, or also to BPD. We investigated whether the hyperoxia known to cause histologic changes in the lungs similar to BPD in an animal model also causes brain and retinal injuries. Sprague Dawley rat pups were exposed to hyperoxia (95% O2, ‘BPD’ group or room air (21% O2, ‘control’ group from postnatal day 4–14 (P4–14; the rat pups were housed in room air between P14 and P28. At P28, they were sacrificed, and their lungs, brain, and eyes were extracted. Hematoxylin and eosin staining was performed on lung and brain sections; retinas were stained with Toluidine Blue. Hyperoxia exposure resulted in an increased mean linear intercept in the lungs (P<0.0001. This increase was associated with a decrease in some brain structures [especially the whole-brain surface (P=0.02], as well as a decrease in the thickness of the retinal layers [especially the total retina (P=0.0008], compared to the room air control group. In addition, a significant negative relationship was observed between the lung structures and the brain (r=−0.49, P=0.02 and retina (r=−0.70, P=0.0008 structures. In conclusion, hyperoxia exposure impaired lung, brain, and retina structures. More severe lung injuries correlated with more severe brain and retinal injuries. This result suggests that the same animal model of chronic neonatal hyperoxia can be used to simultaneously study lung, brain and retinal injuries related to hyperoxia.

  6. Effects of ebselen on ischemia/reperfusion injury in rat brain.

    Science.gov (United States)

    Aras, M; Altaş, M; Meydan, S; Nacar, E; Karcıoğlu, M; Ulutaş, K T; Serarslan, Y

    2014-10-01

    Interruption of blood flow may result in considerable tissue damage via ischemia/reperfusion (I/R) injury-induced oxidative stress in brain tissues. The aim of the present study was to investigate the effects of Ebselen treatment in short-term global brain I/R injury in rats. The study was carried out on 27 Wistar-albino rats, divided into three groups including Sham group (n = 11), I/R group (n = 8) and I/R+Ebselen group (n = 8). Malondialdehyde (MDA) levels were significantly increased in I/R group in comparison with the Sham group and I/R+Ebselen group (p Ebselen (p Ebselen group when compared with Sham group (p Ebselen group when compared with Sham (p Ebselen showed morphological improvement. Ebselen has neuron-protective effects due to its antioxidant properties as shown by the decrease in MDA overproduction, increase in SOD activity and the histological improvement after administration of Ebselen to I/R in brain tissue.

  7. Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments.

    Directory of Open Access Journals (Sweden)

    Kimberly B Zumbrennen-Bullough

    Full Text Available Iron Regulatory Protein 2 (Irp2, Ireb2 is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2-/- mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc, expression are increased and decreased, respectively, in the brain from Irp2-/- mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments.

  8. Brain abscess mimicking brain metastasis in breast cancer.

    Science.gov (United States)

    Khullar, Pooja; Datta, Niloy R; Wahi, Inderjeet Kaur; Kataria, Sabeena

    2016-03-01

    61 year old female presented with chief complaints of headache for 30 days, fever for 10 days, altered behavior for 10 days and convulsion for 2 days. She was diagnosed and treated as a case of carcinoma of left breast 5 years ago. MRI brain showed a lobulated lesion in the left frontal lobe. She came to our hospital for whole brain radiation as a diagnosed case of carcinoma of breast with brain metastasis. Review of MRI brain scan, revealed metastasis or query infective pathology. MR spectroscopy of the lesion revealed choline: creatinine and choline: NAA (N-Acetylaspartate) ratios of ∼1.6 and 1.5 respectively with the presence of lactate within the lesion suggestive of infective pathology. She underwent left fronto temporal craniotomy and evacuation of abscess and subdural empyema. Gram stain showed gram positive cocci. After 1 month of evacuation and treatment she was fine. This case suggested a note of caution in every case of a rapidly evolving space-occupying lesion independent of the patient's previous history. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  9. CNS-syndrome. Characterization of rat brain intermediate filaments

    International Nuclear Information System (INIS)

    Nedzvetskij, V.S.; Busygina, S.G.; Berezin, V.A.; Dvoretskij, A.I.

    1990-01-01

    A study was made of the effect of ionizing radiation on the content and polypeptide composition of filamentous and soluble glial fibrillary acidic protein (GFAP) in different regions of rat brain. Ionizing radiation was shown to decrease considerably the level of soluble GFAP in cerebral cortex, cerebellum, middle brain and hippocampus. Polypeptide composition of soluble GFAP detected by the immonublot-method was found to be changed considerably in different brain areas of irradiated animals

  10. Subarachnoid Hemorrhage Severely Impairs Brain Parenchymal Cerebrospinal Fluid Circulation in Nonhuman Primate.

    Science.gov (United States)

    Goulay, Romain; Flament, Julien; Gauberti, Maxime; Naveau, Michael; Pasquet, Nolwenn; Gakuba, Clement; Emery, Evelyne; Hantraye, Philippe; Vivien, Denis; Aron-Badin, Romina; Gaberel, Thomas

    2017-08-01

    Subarachnoid hemorrhage (SAH) is a devastating form of stroke with neurological outcomes dependent on the occurrence of delayed cerebral ischemia. It has been shown in rodents that some of the mechanisms leading to delayed cerebral ischemia are related to a decreased circulation of the cerebrospinal fluid (CSF) within the brain parenchyma. Here, we evaluated the cerebral circulation of the CSF in a nonhuman primate in physiological condition and after SAH. We first evaluated in physiological condition the circulation of the brain CSF in Macaca facicularis , using magnetic resonance imaging of the temporal DOTA-Gd distribution after its injection into the CSF. Then, animals were subjected to a minimally invasive SAH before an MRI evaluation of the impact of SAH on the brain parenchymal CSF circulation. We first demonstrate that the CSF actively penetrates the brain parenchyma. Two hours after injection, almost the entire brain is labeled by DOTA-Gd. We also show that our model of SAH in nonhuman primate displays the characteristics of SAH in humans and leads to a dramatic impairment of the brain parenchymal circulation of the CSF. The CSF actively penetrates within the brain parenchyma in the gyrencephalic brain, as described for the glymphatic system in rodent. This parenchymal CSF circulation is severely impaired by SAH. © 2017 American Heart Association, Inc.

  11. Local sleep homeostasis in the avian brain: convergence of sleep function in mammals and birds?

    Science.gov (United States)

    Lesku, John A; Vyssotski, Alexei L; Martinez-Gonzalez, Dolores; Wilzeck, Christiane; Rattenborg, Niels C

    2011-08-22

    The function of the brain activity that defines slow wave sleep (SWS) and rapid eye movement (REM) sleep in mammals is unknown. During SWS, the level of electroencephalogram slow wave activity (SWA or 0.5-4.5 Hz power density) increases and decreases as a function of prior time spent awake and asleep, respectively. Such dynamics occur in response to waking brain use, as SWA increases locally in brain regions used more extensively during prior wakefulness. Thus, SWA is thought to reflect homeostatically regulated processes potentially tied to maintaining optimal brain functioning. Interestingly, birds also engage in SWS and REM sleep, a similarity that arose via convergent evolution, as sleeping reptiles and amphibians do not show similar brain activity. Although birds deprived of sleep show global increases in SWA during subsequent sleep, it is unclear whether avian sleep is likewise regulated locally. Here, we provide, to our knowledge, the first electrophysiological evidence for local sleep homeostasis in the avian brain. After staying awake watching David Attenborough's The Life of Birds with only one eye, SWA and the slope of slow waves (a purported marker of synaptic strength) increased only in the hyperpallium--a primary visual processing region--neurologically connected to the stimulated eye. Asymmetries were specific to the hyperpallium, as the non-visual mesopallium showed a symmetric increase in SWA and wave slope. Thus, hypotheses for the function of mammalian SWS that rely on local sleep homeostasis may apply also to birds.

  12. Exercise, cognition, and the adolescent brain.

    Science.gov (United States)

    Herting, Megan M; Chu, Xiaofang

    2017-12-01

    Few adolescents engage in the recommended levels of physical activity, and daily exercise levels tend to drastically decrease throughout adolescence. Beyond physical health benefits, regular exercise may also have important implications for the teenage brain and cognitive and academic capabilities. This narrative review examines how physical activity and aerobic exercise relate to school performance, cognition, and brain structure and function. A number of studies have found that habitual exercise and physical activity are associated with academic performance, cognitive function, brain structure, and brain activity in adolescents. We also discuss how additional intervention studies that examine a wide range of neurological and cognitive outcomes are necessary, as well as characterizing the type, frequency, and dose of exercise and identifying individual differences that contribute to how exercise may benefit the teen brain. Routine exercise relates to adolescent brain structure and function as well as cognitive performance. Together, these studies suggest that physical activity and aerobic exercise may be important factors for optimal adolescent brain development. © 2017 Wiley Periodicals, Inc.

  13. Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli

    Science.gov (United States)

    Field, Brent A.; Buck, Cara L.; McClure, Samuel M.; Nystrom, Leigh E.; Kahneman, Daniel; Cohen, Jonathan D.

    2015-01-01

    Studies of subjective well-being have conventionally relied upon self-report, which directs subjects’ attention to their emotional experiences. This method presumes that attention itself does not influence emotional processes, which could bias sampling. We tested whether attention influences experienced utility (the moment-by-moment experience of pleasure) by using functional magnetic resonance imaging (fMRI) to measure the activity of brain systems thought to represent hedonic value while manipulating attentional load. Subjects received appetitive or aversive solutions orally while alternatively executing a low or high attentional load task. Brain regions associated with hedonic processing, including the ventral striatum, showed a response to both juice and quinine. This response decreased during the high-load task relative to the low-load task. Thus, attentional allocation may influence experienced utility by modulating (either directly or indirectly) the activity of brain mechanisms thought to represent hedonic value. PMID:26158468

  14. Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli.

    Directory of Open Access Journals (Sweden)

    Brent A Field

    Full Text Available Studies of subjective well-being have conventionally relied upon self-report, which directs subjects' attention to their emotional experiences. This method presumes that attention itself does not influence emotional processes, which could bias sampling. We tested whether attention influences experienced utility (the moment-by-moment experience of pleasure by using functional magnetic resonance imaging (fMRI to measure the activity of brain systems thought to represent hedonic value while manipulating attentional load. Subjects received appetitive or aversive solutions orally while alternatively executing a low or high attentional load task. Brain regions associated with hedonic processing, including the ventral striatum, showed a response to both juice and quinine. This response decreased during the high-load task relative to the low-load task. Thus, attentional allocation may influence experienced utility by modulating (either directly or indirectly the activity of brain mechanisms thought to represent hedonic value.

  15. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

    Science.gov (United States)

    Wattanathorn, Jintanaporn; Jittiwat, Jinatta; Tongun, Terdthai; Muchimapura, Supaporn; Ingkaninan, Kornkanok

    2011-01-01

    Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia. PMID:21197427

  16. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2011-01-01

    Full Text Available Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO. Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

  17. Chromium supplementation improved post-stroke brain infarction and hyperglycemia.

    Science.gov (United States)

    Chen, Wen-Ying; Mao, Frank Chiahung; Liu, Chia-Hsin; Kuan, Yu-Hsiang; Lai, Nai-Wei; Wu, Chih-Cheng; Chen, Chun-Jung

    2016-04-01

    Hyperglycemia is common after acute stroke and is associated with a worse outcome of stroke. Thus, a better understanding of stress hyperglycemia is helpful to the prevention and therapeutic treatment of stroke. Chromium is an essential nutrient required for optimal insulin activity and normal carbohydrate and lipid metabolism. Beyond its nutritional effects, dietary supplement of chromium causes beneficial outcomes against several diseases, in particular diabetes-associated complications. In this study, we investigated whether post-stroke hyperglycemia involved chromium dynamic mobilization in a rat model of permanent focal cerebral ischemia and whether dietary supplement of chromium improved post-stroke injury and alterations. Stroke rats developed brain infarction, hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance. Post-stroke hyperglycemia was accompanied by elevated secretion of counter-regulatory hormones including glucagon, corticosterone, and norepinephrine, decreased insulin signaling in skeletal muscles, and increased hepatic gluconeogenesis. Correlation studies revealed that counter-regulatory hormone secretion showed a positive correlation with chromium loss and blood glucose increased together with chromium loss. Daily chromium supplementation increased tissue chromium levels, attenuated brain infarction, improved hyperglycemia, and decreased plasma levels of glucagon and corticosterone in stroke rats. Our findings suggest that stroke rats show disturbance of tissue chromium homeostasis with a net loss through urinary excretion and chromium mobilization a