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Sample records for ageing rat brain

  1. Changes in intracellular calcium in brain cells of aged rats

    Institute of Scientific and Technical Information of China (English)

    Yu Li; Yunpeng Cao

    2008-01-01

    BACKGROUND: Studies have shown that voltage-dependent calcium influx, and enhancement of certain calcium-dependent processes in neurons, is related to aging. OBJECTIVE: To observe changes in intracellular calcium ([Ca2+]i) in neurons of aged rats, and to compare with young rats. DESIGN, TIME AND SETTING: A randomized control experiment of neurophysiology was performed at the Central Laboratory of School of Pharmaceutical Science, China Medical University from June to August 2004. MATERIALS: Ten male, healthy, Wistar rats, 19 months old, were selected for the aged group. Ten male, 3-month-old, Wistar rats were selected for the young control group. Fura-2/AM was provided by the Institute of Pharmaceutical Research of Chinese Academy of Medical Sciences, and the F-2000 fluorospectrophotometer was a product of Hitachi, Japan. METHODS: Fluorescence Fura-2 spectrophotometer was used to measure [Ca2+]i in acutely dissociated brain cells of aged and young rats. The concentration of extracellular potassium was controlled by adding different volumes of chloridated potassium solution of high concentration. MAIN OUTCOME MEASURES: [Ca2+]i in neurons of young and aged rats in the presence of 1 mmol/L extracellular calcium concentration and 0 mmol/L (resting state), 5, 10, 20, and 40 mmol/L extracellular potassium. Absolute increase of [Ca2+]i in neurons of young and aged rats when extraceUular potassium was 5,10,20, 40 mmol/L. RESULTS: In the presence of 1 mmol/L extracellular Ca2+ and 0 mmol/L (resting state), 5, 10, 20, and 40 mmol/L extracellular potassium, [Ca2+]i in the neurons of aged rats was significantly less than that in young rats (P 0.05). CONCLUSION: The overload of [Ca2+]i in neurons of aged rats is greater than that of young rats under the same circumstances.

  2. Fertility, aging and the brain neuroendocrinological studies in female rats

    NARCIS (Netherlands)

    Franke, A.N.

    2003-01-01

    It is well known that fertility decreases in female mammals with advancing age. In women this decrease already starts around the age of 30 and shows a large variation between individuals. The aim of this thesis was to elucidate changes in the reproductive system, especially in the brain, that may un

  3. Combined age- and trauma-related proteomic changes in rat neocortex: a basis for brain vulnerability

    OpenAIRE

    Mehan, Neal D.; Strauss, Kenneth I

    2011-01-01

    This proteomic study investigates the widely observed clinical phenomenon, that after comparable brain injuries, geriatric patients fare worse and recover less cognitive and neurologic function than younger victims. Utilizing a rat traumatic brain injury model, sham surgery or a neocortical contusion was induced in 3 age groups. Geriatric (21 months) rats performed worse on behavioral measures than young adults (12–16 weeks) and juveniles (5– 6 weeks). Motor coordination and certain cognitive...

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

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    José Jaime Herrera-Pérez

    2013-01-01

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

  5. Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats

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    Jian-Qin Wang

    2014-01-01

    Full Text Available Objective. Numerous epidemiological studies have linked diabetes mellitus (DM with an increased risk of developing Alzheimer’s disease (AD. However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ- induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC. Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies.

  6. Maternal separation produces alterations of forebrain brain-derived neurotrophic factor expression in differently aged rats

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    Qiong eWang

    2015-09-01

    Full Text Available Early postnatal maternal separation (MS can play an important role in the development of psychopathologies during ontogeny. In the present study, we investigated the effects of repeated MS (4 h per day from postnatal day [PND] 1–21 on the brain-derived neurotrophic factor (BDNF expression in the medial prefrontal cortex (mPFC, the nucleus accumbens (NAc and the hippocampus of male and female juvenile (PND 21, adolescent (PND 35 and young adult (PND 56 Wistar rats. The results indicated that MS increased BDNF in the CA1 and the dentate gyrus (DG of adolescent rats as well as in the DG of young adult rats. However, the expression of BDNF in the mPFC in the young adult rats was decreased by MS. Additionally, in the hippocampus, there was decreased BDNF expression with age in both the MS and socially reared rats. However, in the mPFC, the BDNF expression was increased with age in the socially reared rats; nevertheless, the BDNF expression was significantly decreased in the MS young adult rats. In the NAc, the BDNF expression was increased with age in the male NMS rats, and the young adult female MS rats had less BDNF expression than the adolescent female MS rats. The

  7. Effect of monoamine nervous transmitter and neuropeptide Y in the aged rats with myocardial injury after brain ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the mechanism of myocardial injury after brain ischemia-reperfusion in aged rats from the changes in Dopamine (DA), Noradrenalin (NE), Epinephrine(E) and Neuropeptide Y(NPY).METHODS: Young (5 months) and aged (20 months or more) rats were divided into model groups and normal control groups, respectively. We observed the following items in rats with 60 minute reperfusion after 30 minute brain ischemia: the pathological changed of myocardium, the activities of lactic dehydrrogenase(LDH), creatine phosphokinase(CPK), the contents of NE, DA, E, NPY. RESULTS:The CPK and LDH activities in the young model rats were higher than those in the young control rats was higher than that in the young control rats (P<0.05). The serum CPK activity in the aged control rats was higher than that in the young control rats (P<0.05). The myocardial CPK activity was higher in the aged model rats compared with the young molel rats (P<0.05) and was higher in aged control rats compared with the young control rats (P<0.01). The myocardial LDH activity was lower in the aged control rats than that in the young control rats (P<0.05) and aged model rats (P<0.01). The serum NE level, the level of NE and DA in the hypothalamus were higher obviously than those in the young control rats. The serum NE contents in the two model groups (young and aged) were higher respectively than the two control rats (young and aged). The following items’ contents were higher in the aged model rats than in the young model rats: serum NE, serum E, hypothalamus NE. The hypothalamus NE and E content was lower in the aged model rats than in te aged control rats. NPY level in the brain tissue was lower in the aged control rats than that in the young control rats and aged model rats (P<0.05).CONCLUSION: The myocardial injury after brain ischemia-reperfusion was concerned with the enhanced excitability of sympathetic-adrenal system, espectially in the aged rats. However, the change in myocardial

  8. Age-related changes in kynurenic acid production in rat brain

    DEFF Research Database (Denmark)

    Gramsbergen, J B; Schmidt, W; Turski, W A;

    1992-01-01

    -dependent increase of KYNA concentration in brain tissue, suggest an enhanced KYNA tone in the aged brain. Together with the reported decline in cerebral excitatory amino acid receptor densities with age, increased production of KYNA may play a role in cognitive and memory dysfunction in old animals....... investigated in tissue slices and was found to be significantly enhanced in the cortex and hippocampus of old animals. The effect of depolarizing agents or sodium replacement was virtually identical in tissues from young and old rats. These data, which are in excellent agreement with reports on an age...... months of age in all five brain regions examined. No changes were observed in the liver. The changes were particularly pronounced in the cortex and in the striatum where enzyme activity increased three-fold during the period studied. KYNA production from its bioprecursor L-kynurenine was also...

  9. Brain nitric oxides synthase in major pelvic ganglia of aged (LETO) and diabetic (OLETF) rats.

    Science.gov (United States)

    Salama, N; Tamura, M; Tsuruo, Y; Ishimura, K; Kagawa, S

    2002-01-01

    This study was conducted to evaluate the effects of aging and diabetes mellitus (DM) on brain nitric oxide synthase (bNOS) expression in major pelvic ganglia (MPG) of rats. Otsuka Long Evans Tokushima Fatty rats (12, 30, and 70 weeks old), which are genetic models with non-insulin-dependent DM (NIDDM), and age-matched nondiabetic Long Evans Tokushima Otsuka controls were used. The MPG of all rats in this study were subjected to cryo-sectioning and staining with bNOS polyclonal AB and rhodamine-conjugated rabbit IgG. Fluorescence intensities of the stained neurons were assessed in randomly selected fields per each specimen. Animals of both groups revealed significant decline in the staining intensity of their neurons with aging and the progress of DM, but diabetic rats showed more decline than controls. In conclusion, both aging and NIDDM could decrease bNOS expression in rat MPG. However, NIDDM has a more evident effect than aging on that expression. The decrease in bNOS may cause a disturbance in functions of the target pelvic structures of these ganglia under both conditions. PMID:12230824

  10. Age dependent accumulation of N-acyl-ethanolamine phospholipids in ischemic rat brain

    DEFF Research Database (Denmark)

    Moesgaard, B.; Petersen, G.; Hansen, Harald S.;

    2000-01-01

    N-acyl-ethanolamine phospholipids (NAPE) can be formed as a stress response during neuronal injury, and they are precursors for N-acyl- ethanolamines (NAE), some of which are endocannabinoids. The levels of NAPE accumulated during post-decapitative ischemia (6 h at 37°C) were studied in rat brains...... of various age (1, 6, 12, 19, 30, and ~70 days) by the use of P NMR spectroscopy of lipid extracts. This ability to accumulate NAPE was compared with the activity of N-acyltransferase and of NAPE-hydrolyzing phospholipase D (NAPE-PLD) in brain microsomes. These two enzymes are involved in the formation...... and degradation of NAPE, respectively. The results showed that 1) the ability to accumulate NAPE during post-decapitative ischemia is especially high in the youngest rats and is markedly reduced in older brains [in 1-day-old rat brains NAPE accumulated to 1.5% of total phospholipids, while in 30-day-old rat...

  11. The effect of ZMS on brain M receptor in aged rats

    International Nuclear Information System (INIS)

    Objective: The purpose of this work was to study the effect of ZMS, an active component of Yin tonic, Zhimu, on brain M2 receptor density of aged animals and its correlation with the effect on learning/memory ability. Methods: A dual-site competitive binding assay using 3H-quinuclidinyl benzilate (QNB) as non selective radioligand and unlabelled Methoctramine as selective competitive agent was established for measuring M2 receptor density in aged rats. Results: In addition to the change of total density of M receptors, the density of a subtype of M receptors, M2 receptor in brain was significantly decreased in aged rats [(231.8 +- 115.9) fmol·mg-1 (x-bar +- s) in young rats and (97.9 +- 46.3) fmol·mg-1 in aged rats]. When the aged rats were treated with ZMS for two months, in addition to the up-regulation of total M receptors, the M2 receptor was up-regulated significantly [being (213 +- 77) mg at a ZMS dose of 3.6 mg·kg-1·d-'1, and (212 +- 72) mg at a ZMS dose of 18 mg·kg-1·d-1]. When the correlation between M2 or total M receptor densities and the learning/memory ability measured by Y-maze performance was examined with linear regression, the correlation coefficient was remarkable (0.721 and 0.505, respectively). Conclusions: ZMS has the ability of up-regulating M2 receptor and this may be an important factor for the improvement of learning and memory by ZMS

  12. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain

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    Sanberg Paul R

    2008-02-01

    Full Text Available Abstract Background Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation. Results We determined that human umbilical cord blood mononuclear cells (UCBMC given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells. This increase in proliferation lasted for at least 15 days after the delivery of the UCBMC. Along with the increase in proliferation following UCBMC treatment, an increase in neurogenesis was also found in the aged animals. The increase in neurogenesis as a result of UCBMC treatment seemed to be due to a decrease in inflammation, as a decrease in the number of activated microglia was found and this decrease correlated with the increase in neurogenesis. Conclusion The results demonstrate that a single intravenous injection of UCBMC in aged rats can significantly improve the microenvironment of the aged hippocampus and rejuvenate the aged neural stem/progenitor cells. Our results raise the possibility of a peripherally administered cell therapy as an effective approach to improve the microenvironment of the aged brain.

  13. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain

    Science.gov (United States)

    Bachstetter, Adam D; Pabon, Mibel M; Cole, Michael J; Hudson, Charles E; Sanberg, Paul R; Willing, Alison E; Bickford, Paula C; Gemma, Carmelina

    2008-01-01

    Background Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation. Results We determined that human umbilical cord blood mononuclear cells (UCBMC) given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells. This increase in proliferation lasted for at least 15 days after the delivery of the UCBMC. Along with the increase in proliferation following UCBMC treatment, an increase in neurogenesis was also found in the aged animals. The increase in neurogenesis as a result of UCBMC treatment seemed to be due to a decrease in inflammation, as a decrease in the number of activated microglia was found and this decrease correlated with the increase in neurogenesis. Conclusion The results demonstrate that a single intravenous injection of UCBMC in aged rats can significantly improve the microenvironment of the aged hippocampus and rejuvenate the aged neural stem/progenitor cells. Our results raise the possibility of a peripherally administered cell therapy as an effective approach to improve the microenvironment of the aged brain. PMID:18275610

  14. Non-injurious neonatal hypoxia confers resistance to brain senescence in aged male rats.

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    Nicolas Martin

    Full Text Available Whereas brief acute or intermittent episodes of hypoxia have been shown to exert a protective role in the central nervous system and to stimulate neurogenesis, other studies suggest that early hypoxia may constitute a risk factor that influences the future development of mental disorders. We therefore investigated the effects of a neonatal "conditioning-like" hypoxia (100% N₂, 5 min on the brain and the cognitive outcomes of rats until 720 days of age (physiologic senescence. We confirmed that such a short hypoxia led to brain neurogenesis within the ensuing weeks, along with reduced apoptosis in the hippocampus involving activation of Erk1/2 and repression of p38 and death-associated protein (DAP kinase. At 21 days of age, increased thicknesses and cell densities were recorded in various subregions, with strong synapsin activation. During aging, previous exposure to neonatal hypoxia was associated with enhanced memory retrieval scores specifically in males, better preservation of their brain integrity than controls, reduced age-related apoptosis, larger hippocampal cell layers, and higher expression of glutamatergic and GABAergic markers. These changes were accompanied with a marked expression of synapsin proteins, mainly of their phosphorylated active forms which constitute major players of synapse function and plasticity, and with increases of their key regulators, i.e. Erk1/2, the transcription factor EGR-1/Zif-268 and Src kinase. Moreover, the significantly higher interactions between PSD-95 scaffolding protein and NMDA receptors measured in the hippocampus of 720-day-old male animals strengthen the conclusion of increased synaptic functional activity and plasticity associated with neonatal hypoxia. Thus, early non-injurious hypoxia may trigger beneficial long term effects conferring higher resistance to senescence in aged male rats, with a better preservation of cognitive functions.

  15. Discovering novel microRNAs and age-related nonlinear changes in rat brains using deep sequencing.

    Science.gov (United States)

    Yin, Lanxuan; Sun, Yubai; Wu, Jinfeng; Yan, Siyu; Deng, Zhenglu; Wang, Jun; Liao, Shenke; Yin, Dazhong; Li, Guolin

    2015-02-01

    Elucidating the molecular mechanisms of brain aging remains a significant challenge for biogerontologists. The discovery of gene regulation by microRNAs (miRNAs) has added a new dimension for examining this process; however, the full complement of miRNAs involved in brain aging is still not known. In this study, miRNA profiles of young, adult, and old rats were obtained to evaluate molecular changes during aging. High-throughput deep sequencing revealed 547 known and 171 candidate novel miRNAs that were differentially expressed among groups. Unexpectedly, miRNA expression did not decline progressively with advancing age; moreover, genes targeted by age-associated miRNAs were predicted to be involved in biological processes linked to aging and neurodegenerative diseases. These findings provide novel insight into the molecular mechanisms underlying brain aging and a resource for future studies on age-related brain disorders.

  16. In vivo molecular imaging of the GABA/benzodiazepine receptor complex in the aged rat brain.

    Science.gov (United States)

    Hoekzema, Elseline; Rojas, Santiago; Herance, Raúl; Pareto, Deborah; Abad, Sergio; Jiménez, Xavier; Figueiras, Francisca P; Popota, Foteini; Ruiz, Alba; Flotats, Núria; Fernández, Francisco J; Rocha, Milagros; Rovira, Mariana; Víctor, Víctor M; Gispert, Juan D

    2012-07-01

    The GABA-ergic system, known to regulate neural tissue genesis during cortical development, has been postulated to play a role in cerebral aging processes. Using in vivo molecular imaging and voxel-wise quantification, we aimed to assess the effects of aging on the benzodiazepine (BDZ) recognition site of the GABA(A) receptor. To visualize BDZ site availability, [(11)C]-flumazenil microPET acquisitions were conducted in young and old rats. The data were analyzed and region of interest analyses were applied to validate the voxel-wise approach. We observed decreased [(11)C]-flumazenil binding in the aged rat brains in comparison with the young control group. More specifically, clusters of reduced radioligand uptake were detected in the bilateral hippocampus, cerebellum, midbrain, and bilateral frontal and parieto-occipital cortex. Our results support the pertinence of voxel-wise quantification in the analysis of microPET data. Moreover, these findings indicate that the aging process involves declines in neural BDZ recognition site availability, proposed to reflect alterations in GABA(A) receptor subunit polypeptide expression.

  17. Effect of a water-maze procedure on the redox mechanisms in brain parts of aged rats

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    Natalia Andreevna Krivova

    2015-03-01

    Full Text Available The Morris water maze (MWM is a tool for assessment of age-related cognitive deficits. In our work, MWM was used for appraisal of cognitive deficits in 11-month-old rats and investigation of the effect exerted by training in the Morris water maze on the redox mechanisms in rat brain parts. Young adult (3-month-old and aged (11-month-old male rats were trained in the water maze. Intact animals of the corresponding age were used as the reference groups. The level of pro- and antioxidant capacity in brain tissue homogenates was assessed using the chemiluminescence method.Cognitive deficits were found in 11-month-old rats: at the first day of training they showed only 30% of successful MWM trials. However, at the last training day the percentage of successful trials was equal for young adult and aged animals. This indicates that cognitive deficits in aged rats can be reversed by MWM training. Therewith, the MWM spatial learning procedure itself produces changes in different processes of redox homeostasis in 11-month-old and 3-month-old rats as compared to intact animals. Young adult rats showed a decrease in prooxidant capacity in all brain parts, while 11-month-old rats demonstrated an increase in antioxidant capacity in the olfactory bulb, pons + medulla oblongata and frontal lobe cortex. Hence, the MWM procedure activates the mechanisms that restrict the oxidative stress in brain parts. The obtained results may be an argument for further development of the animal training procedures aimed to activate the mechanisms responsible for age-related cognitive deficits. This may be useful not only for the development of training procedures applicable to human patients with age-related cognitive impairments, but also for their rehabilitation.

  18. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

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    Yuen-Shan Ho

    Full Text Available Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD. To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.

  19. Age- and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — Differences in various mitochondrial bioenergetics parameters in different brain regions in different age groups. This dataset is associated with the following...

  20. Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats

    Energy Technology Data Exchange (ETDEWEB)

    Kodavanti, Prasada Rao S., E-mail: kodavanti.prasada@epa.gov [Neurotoxicology Branch, Toxicity Assessment Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Royland, Joyce E. [Genetic and Cellular Toxicology Branch, Integrated Systems Toxicology Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Richards, Judy E. [Research Core Unit, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Besas, Jonathan; MacPhail, Robert C. [Neurotoxicology Branch, Toxicity Assessment Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2011-11-15

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), {gamma}-glutamylcysteine synthetase ({gamma}-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at - 80 Degree-Sign C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12 month old rats. These results indicate changes in OS parameters with age and toluene exposure

  1. Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats

    International Nuclear Information System (INIS)

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), γ-glutamylcysteine synthetase (γ-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at − 80 °C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12 month old rats. These results indicate changes in OS parameters with age and toluene exposure resulted in oxidative

  2. Age-related changes in glutathione and glutathione-related enzymes in rat brain

    OpenAIRE

    Zhu, Yuangui; Carvey, Paul M.; Ling, Zaodung

    2006-01-01

    The most reliable and robust risk factor for some neurodegenerative diseases is aging. It has been proposed that processes of aging are associated with the generation of reactive oxygen species and a disturbance of glutathione homeostasis in the brain. Yet, aged animals have rarely been used to model the diseases that are considered to be age-related such as Parkinson's or Alzheimer's disease. This suggests that the results from these studies would be more valuable if aged animals were used. ...

  3. Effects of Early Onset of Nimodipine Treatment on Microvascular Integrity in the Aging Rat Brain

    NARCIS (Netherlands)

    de Jong, Giena; Horváth, E.; Luiten, P.G.M.

    1990-01-01

    We studied the effects of long-term treatment with 1,4-dihydropyridine nimodipine on age-related changes of the cerebral microvasculature in layers I, III, and V of the frontoparietal motor cortex of aged (30 months) male Wistar rats. Ultrastructural alterations of microvessels can either be attribu

  4. Postnatal Age Influences Hypoglycemia-induced Poly(ADP-ribose) Polymerase-1 Activation in the Brain Regions of Rats

    OpenAIRE

    Rao, Raghavendra; Sperr, Dustin; Ennis, Kathleen; Tran, Phu

    2009-01-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) overactivation plays a significant role in hypoglycemia-induced brain injury in adult rats. To determine the influence of postnatal age on PARP-1 activation, developing and adult male rats were subjected to acute hypoglycemia of equivalent severity and duration. The expression of PARP-1 and its downstream effectors, apoptosis inducing factor (Aifm1), caspase 3 (Casp3), NF-κB (Nfkb1) and bcl-2 (Bcl2), and cellular poly(ADP-ribose) (PAR) polymer expression...

  5. Age and heat exposure-dependent changes in antioxidant enzymes activities in rat's liver and brain mitochondria: role of alpha-tocopherol.

    Science.gov (United States)

    Stojkovski, V; Hadzi-Petrushev, N; Ilieski, V; Sopi, R; Gjorgoski, I; Mitrov, D; Jankulovski, N; Mladenov, M

    2013-01-01

    To investigate the role of mitochondrial antioxidant capacity during increased susceptibility to heat accompanied by the aging, young and aged Wistar rats were exposed on heat for 60 min. After heat exposure, hepatic and brain mitochondria were isolated. Our results revealed changes in antioxidant enzyme activities in liver and brain mitochondria from young and to a greater extent in aged rats. Our measurements of MnSOD, GPx and GR activity indicate greater reactive oxygen species production from the mitochondria of aged heat exposed in comparison to young heat exposed rats. Also in the aged rats, the effect of alpha-tocopherol treatment in the prevention of oxidative stress occurred as a result of heat exposure, is less pronounced. Taken together, our data suggest that mitochondria in aged rats are more vulnerable and less able to prevent oxidative changes that occur in response to acute heat exposure.

  6. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Science.gov (United States)

    Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

  7. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Directory of Open Access Journals (Sweden)

    Kun Hua

    Full Text Available Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like

  8. Calcium antagonists decrease capillary wall damage in aging hypertensive rat brain

    NARCIS (Netherlands)

    Farkas, E.; de Jong, G.I.; Apro, E.; Keuker, J.I.H.; Luiten, P.G.M.

    2001-01-01

    Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillar

  9. Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats.

    Science.gov (United States)

    Singh, Rumani; Manchanda, Shaffi; Kaur, Taranjeet; Kumar, Sushil; Lakhanpal, Dinesh; Lakhman, Sukhwinder S; Kaur, Gurcharan

    2015-12-01

    Intermittent fasting dietary restriction (IF-DR) is recently reported to be an effective intervention to retard age associated disease load and to promote healthy aging. Since sustaining long term caloric restriction regimen is not practically feasible in humans, so use of alternate approach such as late onset short term IF-DR regimen which is reported to trigger similar biological pathways is gaining scientific interest. The current study was designed to investigate the effect of IF-DR regimen implemented for 12 weeks in middle age rats on their motor coordination skills and protein and DNA damage in different brain regions. Further, the effect of IF-DR regimen was also studied on expression of energy regulators, cell survival pathways and synaptic plasticity marker proteins. Our data demonstrate that there was an improvement in motor coordination and learning response with decline in protein oxidative damage and recovery in expression of energy regulating neuropeptides. We further observed significant downregulation in nuclear factor kappa B (NF-κB) and cytochrome c (Cyt c) levels and moderate upregulation of mortalin and synaptophysin expression. The present data may provide an insight on how a modest level of short term IF-DR, imposed in middle age, can slow down or prevent the age-associated impairment of brain functions and promote healthy aging by involving multiple regulatory pathways aimed at maintaining energy homeostasis. PMID:26318578

  10. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain.

    Science.gov (United States)

    Lee, Ho-Sung; Kang, Dai-In; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Inhyung; Kim, Hoon-Gi; Lee, Byung-Cheon; Lee, Ki Bog

    2015-07-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix. PMID:26330833

  11. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

    Directory of Open Access Journals (Sweden)

    Ho-Sung Lee

    2015-01-01

    Full Text Available With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix.

  12. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

    Institute of Scientific and Technical Information of China (English)

    Ho-Sung Lee; Dai-In Kang; Seung Zhoo Yoon; Yeon Hee Ryu; Inhyung Lee; Hoon-Gi Kim; Byung-Cheon Lee; Ki Bog Lee

    2015-01-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-depen-dent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-depen-dent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increas-ing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix.

  13. Effect of propofol on brain-derived neurotrophic factor and tyrosine kinase receptor B in the hippocampus of aged rats with chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Gang Chen; Qiang Fu; Jiangbei Cao; Weidong Mi

    2012-01-01

    We intraperitoneally injected 10 and 50 mg/kg of propofol for 7 consecutive days to treat a rat model of chronic cerebral ischemia. A low-dose of propofol promoted the expression of brain-derived neurotrophic factor, tyrosine kinase receptor B, phosphorylated cAMP response element binding protein, and cAMP in the hippocampus of aged rats with chronic cerebral ischemia, but a high-dose of propofol inhibited their expression. Results indicated that the protective effect of propofol against cerebral ischemia in aged rats is related to changes in the expression of brain-derived neurotrophic factor and tyrosine kinase receptor B in the hippocampus, and that the cAMP-cAMP responsive element binding protein pathway is involved in the regulatory effect of propofol on brain-derived neurotrophic factor expression.

  14. The neuron-astrocyte-microglia triad in normal brain ageing and in a model of neuroinflammation in the rat hippocampus.

    Directory of Open Access Journals (Sweden)

    Francesca Cerbai

    Full Text Available Ageing is accompanied by a decline in cognitive functions; along with a variety of neurobiological changes. The association between inflammation and ageing is based on complex molecular and cellular changes that we are only just beginning to understand. The hippocampus is one of the structures more closely related to electrophysiological, structural and morphological changes during ageing. In the present study we examined the effect of normal ageing and LPS-induced inflammation on astroglia-neuron interaction in the rat hippocampus of adult, normal aged and LPS-treated adult rats. Astrocytes were smaller, with thicker and shorter branches and less numerous in CA1 Str. radiatum of aged rats in comparison to adult and LPS-treated rats. Astrocyte branches infiltrated apoptotic neurons of aged and LPS-treated rats. Cellular debris, which were more numerous in CA1 of aged and LPS-treated rats, could be found apposed to astrocytes processes and were phagocytated by reactive microglia. Reactive microglia were present in the CA1 Str. Radiatum, often in association with apoptotic cells. Significant differences were found in the fraction of reactive microglia which was 40% of total in adult, 33% in aged and 50% in LPS-treated rats. Fractalkine (CX3CL1 increased significantly in hippocampus homogenates of aged and LPS-treated rats. The number of CA1 neurons decreased in aged rats. In the hippocampus of aged and LPS-treated rats astrocytes and microglia may help clearing apoptotic cellular debris possibly through CX3CL1 signalling. Our results indicate that astrocytes and microglia in the hippocampus of aged and LPS-infused rats possibly participate in the clearance of cellular debris associated with programmed cell death. The actions of astrocytes may represent either protective mechanisms to control inflammatory processes and the spread of further cellular damage to neighboring tissue, or they may contribute to neuronal damage in pathological conditions.

  15. Late-onset intermittent fasting dietary restriction as a potential intervention to retard age-associated brain function impairments in male rats

    OpenAIRE

    Singh, Rumani; Lakhanpal, Dinesh; Kumar, Sushil; Sharma, Sandeep; Kataria, Hardeep; Kaur, Manpreet; Kaur, Gurcharan

    2011-01-01

    Lifelong dietary restriction (DR) is known to have many potential beneficial effects on brain function as well as delaying the onset of neurological diseases. In the present investigation, the effect of late-onset short-term intermittent fasting dietary restriction (IF-DR) regimen was studied on motor coordination and cognitive ability of ageing male rats. These animals were further used to estimate protein carbonyl content and mitochondrial complex I–IV activity in different regions of brain...

  16. Age-related learning and memory deficits in rats: role of altered brain neurotransmitters, acetylcholinesterase activity and changes in antioxidant defense system

    OpenAIRE

    Haider, Saida; Saleem, Sadia; Perveen, Tahira; Tabassum, Saiqa; Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Madiha, Syeda

    2014-01-01

    Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino–Wistar rats at age of 4 and 24 months. Th...

  17. Age-and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    Science.gov (United States)

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cereb...

  18. Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats

    Institute of Scientific and Technical Information of China (English)

    LI Ying; JI Yong-juan; JIANG Hong; LIU De-xiang; ZHANG Qian; FAN Shu-jian; PAN Fang

    2009-01-01

    Background Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats. Methods Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Results Age and stress had different effects on the behavior of different aged animals (age: F=6.173, P <0.05, stress: F=6.056, P <0.05). Stress was the main factor affecting sucrose preference (F=123.608, P <0.05). Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals (P <0.05). The older stress rats showed a lower sucrose preference than young stress rats (P <0.05). Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square (P <0.05), exhibiting fewer vertical movements (P <0.05) and less grooming (P <0.05). Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress

  19. Systemic Effects of Fractionated, Whole-Brain Irradiation in Young Adult and Aging Rats

    OpenAIRE

    Forbes, M. E.; Paitsel, M.; Bourland, J. D.; Riddle, D. R.

    2013-01-01

    Cranial irradiation is a critical and effective treatment for primary brain tumors and metastases. Unfortunately, most patients who are treated and survive for more than a few months develop neural and cognitive problems as the result of radiation-induced normal tissue injury. The neurobiological mechanisms underlying these cognitive deficits remain largely unknown and there are no validated treatments to prevent or ameliorate them; thus, there is a significant and continuing need for preclin...

  20. EFFECTS OF TOLUENE ON BRAIN OXIDATIVE STRESS PARAMETERS IN AGING BROWN NORWAY RATS

    Science.gov (United States)

    Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for tol...

  1. TOXICITY PATHWAY ANALYSIS IN AGING BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    Science.gov (United States)

    The influence of aging on susceptibility to environmental stressors is poorly understood. To investigate the contribution of different life stages on response to toxicants, we examined the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.3...

  2. Effects of ginsenoside on brain-derived neurotrophic factor and tyrosine kinase B mRNA expression in the hippocampal formation of aged rats

    Institute of Scientific and Technical Information of China (English)

    Hong Lai; Wensu Liu; Zhaosheng Li; Haihua Zhao; Yongli Lü

    2008-01-01

    BACKGROUND:There are a limited number of studies involving the effects of ginsenosides,the active component of ginseng,on expression of hippocampal TrkB mRNA in aged rats.OBJECTIVE:To observe expression of brain-derived neurotrophic factor(BDNF) and tyrosine kinase B (TrkB)mRNA in the hippocampal formation of aged rats,as well as changes after ginsenoside administrated.DESIGN,TIME AND SETTING:A randomized,controlled experiment was performed at the Department of Anatomy,College of Basic Medical Sciences,China Medical University in March 2005.MATERIALS:A total of 39 female,Wistar rats were randomly divided into 3 groups (n=13 each):young (3-5 months old),aged(27 months old),and ginsenoside group(received 25mg/kg/d ginsenoside in the drinking water between 17 and 27 months of age).METHODS:Following anesthesia,the rats were exsanguinated and perfused transcardially with chilled,heparinized,0.9% saline.The brains were removed and post-fixed in 40 g/L paraformaldehyde/phosphate buffer for 20 minutes,and further incubated in 30% sucrose/phosphate buffer overnight.MAIN OUTCOME MEASURES:In situ hybridization,immunohistochemistry,and image analysis were used to investigate expression of BDNF and Trk(B mRNA in the hippocampal formation.RESULTS:The expression levels of BDNF in the hippocampal CA3 and CA1 of aged rats was significantly less than the young group(t=2.879,1.814,1.984,P<0.05).BDNF expression was significantly greater in the dentate gyrus of the ginsenoside group,compared with the aging group(t=1.943,P<0.01).The expression of TrkB mRNA in the hippocampal CA3,CA1,and dentate gyrus of aged rats was less than the young group(t=3.540,3.629,17.905,P<0.01).TrkB mRNA expression in the CA3 region and dentate gyrus of the ginsenoside group was significantly greater compared with the aging group(t=1.293,3.386,P<0.05.0.01).CONCLUSION:BDNF and TrkB mRNA expression in the hippocampal formation were reduced in the aged group.However,ginsenosides can increase BDNF and TrkB m

  3. Cognition and brain functional aging

    Directory of Open Access Journals (Sweden)

    Hui-jie LI

    2014-03-01

    Full Text Available China has the largest population of elderly adults. Meanwhile, it is one of the countries showing fastest aging speed in the world. Aging processing is always companied with a series of brain structural and functional changes, which result in the decline of processing speed, working memory, long-term memory and executive function, etc. The studies based on functional magnetic resonance imaging (fMRI found certain aging effects on brain function activation, spontaneous activity and functional connectivity in old people. However, few studies have explored the brain functional curve during the aging process while most previous studies explored the differences in the brain function between young people and old people. Delineation of the human brain functional aging curve will promote the understanding of brain aging mechanisms and support the normal aging monitoring and early detection of abnormal aging changes. doi: 10.3969/j.issn.1672-6731.2014.03.005

  4. Post-Stroke Infections Exacerbate Ischemic Brain Injury in Middle-Aged Rats: Immunomodulation and Neuroprotection by Progesterone

    OpenAIRE

    Yousuf, Seema; Atif, Fahim; Sayeed, Iqbal; Wang, Jun; Stein, Donald G.

    2012-01-01

    We investigated the effect of delayed, prolonged systemic inflammation on stroke outcomes and progesterone (P4) neuroprotection in middle-aged rats. After transient middle cerebral artery occlusion/reperfusion (MCAO) surgery, rats received P4 (8 or 16 mg/kg) or vehicle injections at 2h, 6h and every 24h until day 7 post-occlusion. At 24h post-injury systemic inflammation was induced by giving 3 doses of lipopolysaccharide (LPS; 50 mg/kg, at 4h intervals) to model post-stroke infections. We me...

  5. Effect of Ligustrazine and Shenmai Injection on ATPase and free radical metabolism in the aged rats with myocardial injury after brain ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the protecitve mechanism of Ligustrazine (LT), Shenmai Parenteral Injection (SPI), combination of Ligustrazine and Shenmai Parenteral Injection (LSP) to myocardial injury after brain ischemia-reperfusion in aged rats from the change in ATPase and free radical in order to provide theoretical basic for prevention and cure of cerebral infarction. METHODS: Aged rats (more than 20 months) were divided into model group, control group, Nimotop group, LT group, SPI group and LSP group. We measured the following items in aged rats with 60 min of reperfusion after 30 min of brain ischemia: the content of MDA, the activities of superoxide dismutase (SOD), lactic dehydrrogenase (LDH), creatine phosphokinase (CPK), ATPase. RESUTLS: The CPK and LDH activities in the model rats increased obviously. The serum CPK activity in the LSP group, the LT group, nimotop group was lower than those in the model group obviously. The serum LDH activities in LT group and SPI group were obviously lower compared with those in the model group. The activity of Na+-K+-ATPase and Ca2+-ATPase in model group was decreased. Contrast to the model group, the activity of Na+-K+-ATPase in LSP group, Nimotop group, LT group and the activities of Ca2+-ATPase in the LSP group were higher. The serum MDA/SOD ratio was larger than that in the control group. The decrease in myocardial SOD activity and the increase in the MDA level, MDA/SOD ratio in the model group showed significant difference compared with that in the control. The MDA level in the LSP group was lower than that in the model group. The increase in myocardial SOD activity and decrease in MDA, MDA/SOD ratio were obvious in the LSP group compared with the model group. CONCLUSION: The myocardial injury after brain ischemia-reperfusion in aged rats was related to the decrease in the activity of Na+-K+-ATPase and injury of free radical. LT, SPI, LSP and Nimotop could prevent this inury. Nimotop and LT could enhanced the

  6. Standardized extract of Bacopa monniera (BESEB CDRI-08) attenuates contextual associative learning deficits in the aging rat's brain induced by D-galactose.

    Science.gov (United States)

    Prisila Dulcy, Charles; Singh, Hemant K; Preethi, Jayakumar; Rajan, Koilmani Emmanuvel

    2012-10-01

    In this study, we examined the neuroprotective effect of standardized Bacopa monniera extract (BME: BESEB CDRI-08) against the D-galactose (D-gal)-induced brain aging in rats. Experimental groups were subjected to contextual-associative learning task. We found that the administration of BME in the D-gal-treated group attenuated contextual-associative learning deficits; the individuals showed more correct responses and retrieved the reward with less latency. Subsequent analysis showed that the BME administration significantly decreased advance glycation end product (AGE) in serum and increased the activity of antioxidant response element (ARE) and the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and nuclear transcription factor NF-E2-related factor 2 (Nrf2), accompanied by a reduction in the level of serotonin (5-HT) in the hippocampus. The BME treatment also reversed D-gal-induced brain aging by upregulating the levels of the presynaptic proteins synaptotagmin I (SYT1) and synaptophysin (SYP) and the postsynaptic proteins Ca(2+) /calmodulin dependent protein kinase II (αCaMKII) and postsynaptic density protein-95 (PSD-95) in the hippocampus during synaptic plasticity. A significant finding is that the D-gal- + BME-treated rats exhibited more correct responses in contextual-associative learning than D-gal alone-treated rats. Our findings suggest that BME treatment attenuates D-gal-induced brain aging and regulates the level of antioxidant enzymes, Nrf2 expression, and the level of 5-HT, which was accompanied by concomitantly increased levels of synaptic proteins SYT1, SYP, αCaMKII, p-αCaMKII, and PSD-95. PMID:22715050

  7. nNOS expression of hippocampal neurons in aged rats after brain ischemia/reperfusion and its role in DND development

    Institute of Scientific and Technical Information of China (English)

    杨传红; 赖晃文; 詹纯列; 肖育华; 郑文岭

    2002-01-01

    To study the role of neuronal nitric oxide synthase (nNOS) in aged rats' hippocampal delayed neuronal death (DND) following brain ischemia. Methods: Models of incomplete brain ischemia were induced by clipping common carotid artery. A total of 46 aged SD rats were divided into 8 groups: normal control group ( Group A, n = 5 ), sham-operation group ( Group B, n = 5), reperfusion 1, 6, 12, 24, 48, and 96 hours groups after brain ischemia for 30 minutes ( Group C, D,E, F, G, and H, n = 6/group). The expression of nNOS was examined by immunohistochemistry and neuronal ultrastructural changes were observed by the transmission electron microscopy (TEM) at different time points after reperfusion. Results: Immunohistochemistry showed that nNOS expression in the hippocampal neurons was high in Group E, iow expression in Group D, moderate expression in Group F and G. There was nearly no expression of nNOS in Group A, B, C, and H. UItrastructure of hippocampal neurons was damaged more severely in reperfusion over 24 hours groups. Conclusions: Nitric oxide (NO) may be one of the important factors in inducing DND after ischemia/reperfusion.

  8. The effects of omega 3 fatty acid supplementation on brain tissue oxidative status in aged wistar rats

    OpenAIRE

    Avramovic, N; Dragutinovic, V; Krstic, D; Colovic, MB; Trbovic, A; de Luka, S; Milovanovic, I; Popovic, T

    2012-01-01

    Background: The omega 3 fatty acids play an important role in many physiological processes. Their effect is well documented in neurodegenerative diseases and inflammatory diseases. Also, aging as a biophysiological process could be influenced by eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) components of fish oil. However there are not many studies showing the effect of PUFA (polyunsaturated FA) suplementation in eldery brain functions and the response to oxidative strees. The aim ...

  9. H2O2-mediated DNA damage and repair in the brain cells in the aging rats detected by comet assay

    Institute of Scientific and Technical Information of China (English)

    Suming ZhangM.D., Ph.D; Zongchao Han, M.D.; Siyu Fang, M.D.; Ruan Yang, M.D; Wei Wang, M.D., Ph. D

    2000-01-01

    Objective: To identify the relation between DNA damage susceptibility/ DNA repair capability and aging process after insults, an observation of H2O2_induced DNA damage and the kinetics of DNA repair in senescent murine brain cells with the alkaline single cell gel electrophoresis (SCGE/Comet assay) was made. Methods: The dissociated brain cells harvested in the area of the cerebral cortex, hippocampus, basal gang]ion from 3-month (n=10), 8-month (n=8) and 26-month (n=5) old rats were respectively treated with H2O2 in gradient doses for 10 min, or without H2O2 as controls. The cells embedded in agarose were lysed, helix-untied, electrophoresed, stained with a fluorescence DNA binding stain, viewed under a fluorescence microscope. Individual image was optically recorded. The frequency of the tailed cells and the grade of tails wereused to analyze single strand breaks of DNA and injury intensity. Results: By the cell and DNA image like comets, a linear increase was noticed in vulnerability of DNA both to H2O2 doses and to the age. Regarding the damaged region of the brain, the cortex cells were more vulnerable to the insult than the hippocampus/basal ganglionic cells. Whatever aging or not the cells were, the maximum of ratio of DNA repair was only within 1 hour during the incubation for 0.5-4 hours after the insults. Furthermore, the more aging, the less ratio of DNA repair of sick cells. Conclusion: The DNA damagesusceptibility and the DNA repair capability of individual cells, whatever its age is, can be detected by this brain cell injury model. Comet assay is a sensitive way to find out DNA damage and repair of the cells. It should be more difficult for the cells to cope with an acute and excessive than with a persistent, chronic and mild DNA damage which is more related to an accumulating injury, the aging.

  10. Influence of ginsenoside on expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in the medial septum of aged rats

    Institute of Scientific and Technical Information of China (English)

    Liang Zeng; Haihua Zhao; Yongli Lü; Wenbo Dai

    2008-01-01

    BACKGROUND: It has been shown that ginsenoside, the effective component of ginseng, can enhance expression of choline acetyl transferase, as well as brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB), in cholinergic neurons of the basal forebrain.OBJECTIVE: To qualitatively and quantitatively verify the influence of ginsenoside on expression of BDNF and its receptor, TrkB, in the medial septum of aged rats, and to provide a molecular basis for clinical application.DESIGN, TIME AND SETTING: A contrast study, which was performed in the Department of Anatomy, China Medical University, and the Department of Anatomy, Shenyang Medical College between December 2005 and May 2007.MATERIALS: Thirty-five, healthy, female, Sprague Dawley rats were selected for this study. Ginsenoside (81% purity) was provided by Jilin Ji'an Wantai Chinese Medicine Factory; anti-BDNF antibody, anti-TrkB antibody, and their kits were provided by Wuhan Boster Company.METHODS: A total of 35 rats were divided into three groups: young (four months old), aging (26 months old), and ginsenoside. Rats in the ginsenoside group were administered ginsenoside (25mg/kg/d) between 17 months and 26 months.MAIN OUTCOME MEASURES: Immunohistochemistry and in situ hybridization were used to measure expression of BDNF and TrkB in the medial septum of aged rats, and the detected results were expressed as gray values.RESULTS: ①Qualitative detection: using microscopy, degenerative neurons were visible in the medial septum in the aging group. However, neuronal morphology in the ginsenoside group was similar to neurons in the young group.②Quantitative detection: the mean gray value of BDNF-positive and TrkB-positive products in the aging group were significantly higher than in the young group (t=3.346,4.169, P<0.01); however, the mean gray value in the ginsenoside group was significantly lower than in the aging group (t=2.432,2.651, P<0.01).CONCLUSION: Ginsenoside can increase

  11. Brain aging and therapeutic interventions

    DEFF Research Database (Denmark)

    This book brings together most up-to-date information on different aspects of brain aging and on the strategies for intervention and therapy of age-related brain disorders. It includes 18 chapters by leading researchers, and each chapter is a comprehensive and critical review of the topic...

  12. Neurogenesis in the aging brain

    Directory of Open Access Journals (Sweden)

    Veronica Galvan

    2007-01-01

    Full Text Available Veronica Galvan, Kunlin JinBuck Institute for Age Research, 8001 Redwood Blvd. Novato, CA, USAAbstract: Neurogenesis, or the birth of new neural cells, was thought to occur only in the developing nervous system and a fixed neuronal population in the adult brain was believed to be necessary to maintain the functional stability of adult brain circuitry. However, recent studies have demonstrated that neurogenesis does indeed continue into and throughout adult life in discrete regions of the central nervous systems (CNS of all mammals, including humans. Although neurogenesis may contribute to the ability of the adult brain to function normally and be induced in response to cerebral diseases for self-repair, this nevertheless declines with advancing age. Understanding the basic biology of neural stem cells and the molecular and cellular regulation mechanisms of neurogenesis in young and aged brain will allow us to modulate cell replacement processes in the adult brain for the maintenance of healthy brain tissues and for repair of disease states in the elderly.Keywords: neurogenesis, aging, brain, neural stem cells, subgranular zone, subventricular zone

  13. Blood brain barrier and neuroinflammation are critical targets of IGF-1-mediated neuroprotection in stroke for middle-aged female rats.

    Directory of Open Access Journals (Sweden)

    Shameena Bake

    Full Text Available Ischemia-induced cerebral infarction is more severe in older animals as compared to younger animals, and is associated with reduced availability of insulin-like growth factor (IGF-1. This study determined the effect of post-stroke IGF-1 treatment, and used microRNA profiling to identify mechanisms underlying IGF-1's neuroprotective actions. Post-stroke ICV administration of IGF-1 to middle-aged female rats reduced infarct volume by 39% when measured 24h later. MicroRNA analyses of ischemic tissue collected at the early post-stroke phase (4h indicated that 8 out of 168 disease-related miRNA were significantly downregulated by IGF-1. KEGG pathway analysis implicated these miRNA in PI3K-Akt signaling, cell adhesion/ECM receptor pathways and T-and B-cell signaling. Specific components of these pathways were subsequently analyzed in vehicle and IGF-1 treated middle-aged females. Phospho-Akt was reduced by ischemia at 4h, but elevated by IGF-1 treatment at 24h. IGF-1 induced Akt activation was preceded by a reduction of blood brain barrier permeability at 4h post-stroke and global suppression of cytokines including IL-6, IL-10 and TNF-α. A subset of these cytokines including IL-6 was also suppressed by IGF-1 at 24h post-stroke. These data are the first to show that the temporal and mechanistic components of post-stroke IGF-1 treatment in older animals, and that cellular components of the blood brain barrier may serve as critical targets of IGF-1 in the aging brain.

  14. Surgery-induced hippocampal angiotensin II elevation causes blood-brain barrier disruption via MMP/TIMP in aged rats

    Directory of Open Access Journals (Sweden)

    Zhengqian eLi

    2016-04-01

    Full Text Available Reversible BBB disruption has been uniformly reported in several animal models of postoperative cognitive dysfunction (POCD. Nevertheless, the precise mechanism underlying this occurrence remains unclear. Using an aged rat model of POCD, we investigated the dynamic changes in expression of molecules involved in BBB disintegration, matrix metalloproteinase-2 (MMP-2 and -9 (MMP-9, as well as three of their endogenous tissue inhibitors (TIMP-1, -2, -3, and tried to establish the correlation between MMP/TIMP balance and surgery-induced hippocampal BBB disruption. We validated the increased hippocampal expression of angiotensin II (Ang II and Ang II receptor type 1 (AT1 after surgery. We also found MMP/TIMP imbalance as early as 6 h after surgery, together with increased BBB permeability and decreased expression of Occludin and zonula occludens-1 (ZO-1, as well as increased basal lamina protein laminin at 24 h postsurgery. The AT1 antagonist candesartan restored MMP/TIMP equilibrium and modulated expression of Occludin and laminin, but not ZO-1, thereby improving BBB permeability. These events were accompanied by suppression of the surgery-induced canonical nuclear factor-κB (NF-κB activation cascade. Nevertheless, AT1 antagonism did not affect nuclear receptor peroxisome proliferator-activated receptor-γ expression. Collectively, these findings suggest that surgery-induced Ang II release impairs BBB integrity by activating NF-κB signaling and disrupting downstream MMP/TIMP balance via AT1 receptor.

  15. Nutrients, Microglia Aging, and Brain Aging

    OpenAIRE

    Zhou Wu; Janchun Yu; Aiqin Zhu; Hiroshi Nakanishi

    2016-01-01

    As the life expectancy continues to increase, the cognitive decline associated with Alzheimer’s disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and ...

  16. Age-dependent actions of dexamethasone on the development of focal hypoxic-ischemic brain in new-born and adult rats

    International Nuclear Information System (INIS)

    Complete text of publication follows. The pharmacotherapy of hypoxic-ischemic (H-I) brain oedema is poorly characterized. Several clinical trials have shown that glucocorticoids exert a harmful effect in patients with cerebral ischemia, but others have described opposite results. The mechanism of H-I brain oedema and cell death is not fully elucidated yet. It is well-known that glucocorticoids have membrane stabilizing and antioxidants properties. These types of steroids may indirectly act on different enzymes playing role in H-I damage. The hypoxic brain oedema is associated with impaired water metabolism and brain water electrolyte contents change. The aim of the present study was to examine whether the neuroprotective effect of the dexamethasone on focal H-I cytotoxic and vasogenic brain oedema depends on its penetration into the brain tissue or is exerted by other mechanisms. We measured the effect of glucocorticoid dexamethasone, antiglucocorticoid mifepristone (RU 486) and their combination on focal H-I cytotoxic and vasogenic brain oedema in neonate and adult rats. We also studied different calcium-channel inhibitors influence on the survival of the H-I animals. Mifepristone alone had no effect however antagonized the inhibitory effect of dexamethasone in ipsilateral hemisphere of 1-week old rats. Our work demonstrates that dexamethasone can penetrate into both ipsilateral and contralateral hemispheres of the one and two-weeks-old rats but not in 4 or 12-weeks-old animals. Thus, the results suggest that the site of protective action of dexamethasone is in the brain tissue and the penetration of it depends on the total development of blood-brain barrier.

  17. Melatonin Counteracts at a Transcriptional Level the Inflammatory and Apoptotic Response Secondary to Ischemic Brain Injury Induced by Middle Cerebral Artery Blockade in Aging Rats

    OpenAIRE

    Paredes, Sergio D.; Rancan, Lisa; Kireev, Roman; González, Alberto; Louzao, Pedro; González, Pablo; Rodríguez-Bobada, Cruz; García, Cruz; Vara, Elena; Tresguerres, Jesús A.F.

    2015-01-01

    Abstract Aging increases oxidative stress and inflammation. Melatonin counteracts inflammation and apoptosis. This study investigated the possible protective effect of melatonin on the inflammatory and apoptotic response secondary to ischemia induced by blockade of the right middle cerebral artery (MCA) in aging male Wistar rats. Animals were subjected to MCA obstruction. After 24 h or 7 days of procedure, 14-month-old nontreated and treated rats with a daily dose of 10 mg/kg melatonin were s...

  18. TOLUENE EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF YOUNG-ADULT, MIDDLE-AGE AND SENESCENT BROWN NORWAY RATS

    Science.gov (United States)

    Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for tol...

  19. Aquaporin 9 in rat brain after severe traumatic brain injury

    OpenAIRE

    Hui Liu; Mei Yang; Guo-ping Qiu; Fei Zhuo; Wei-hua Yu; Shan-quan Sun; Yun Xiu

    2012-01-01

    OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9) in rat brain, after severe traumatic brain injury (TBI). METHODS: Brain water content (BWC), tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC), immunofluorescence (IF), western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest) peaks at 6 and 72 hours, and the blood brain barrier (BBB) was severely destroyed at six hours after ...

  20. Aluminum neurotoxicity in the rat brain

    International Nuclear Information System (INIS)

    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)

  1. Effect of DHA on Antioxidation and Fatty Acids in Aged Rat Brain%二十二碳六烯酸对老年大鼠脑组织抗氧化和脂肪酸的影响

    Institute of Scientific and Technical Information of China (English)

    蒋利和; 马博; 谢正轶; 杨志荣

    2011-01-01

    Objective:To explore the antioxidant mechanisms of DHA in the brain of aged rats.Methods:Wistar male rats were randomly divided into four groups including 7-month-old adult group,20-month-old aged group,and low-dose and high-dose DHA-treated 20-month-old aged groups at the respective doses of 180 mg/(kg·d) and 360 mg/(kg·d)(administered by gavage for 42 consecutive days).At the end of the administration period,all rats were sacrificed and the activities of superoxide dismutase(SOD),gtutathione peroxidase(GSH-Px) and catalase(CAT) and the level of malondialdehyde(MDA) were assayed in brain.In addition,the fatty acid profile in brain was analyzed by gas chromatography-mass spectrometry,and the phospholipid composition was also analyzed by thin layer chromatography and phosphomolybdate methods.Results:Compared with the aged group,the activities of SOD,GSH-Px and CAT in the brain of the DHA-treated groups were significantly increased and MDA content was significantly decreased.Fatty acid analysis showed that DHA-treated rats exhibited an obvious increase in the ratio of total n-3 fatty acids to total n-6 fatty acids and the ratio of DHA to arachidonic acid(AA) and an obvious reduction in AA level.It was also revealed that DHA could improve the levels of phosphatidylcholine,phosphatidylethanolamine,phosphatidylinositol,phosphatidylserine and sphingomgelins in the brain of rats.Conclusion:DHA can obviously improve antioxidant capacity in aged rats and its antioxidant mechanism may be due to DHA-induced change of fatty acid profile in the brain.%目的:研究二十二碳六烯酸(DHA)改善老年大鼠抗氧化的可能机制。方法:动物分为青年组(7月龄青年雄性大鼠)、老年组(20月龄雄性大鼠)、DHA低剂量组(灌喂20月龄雄性大鼠DHA 180mg/(kg.d)42d)、DHA高剂量组(灌喂20月龄雄性大鼠360mg/(kg.d)42d),处死大鼠后测定脑组织中超氧化物歧化酶

  2. NIH Conference. Brain imaging: aging and dementia

    International Nuclear Information System (INIS)

    The brain imaging techniques of positron emission tomography using [18F]-fluoro-2-deoxy-D-glucose, and computed tomography, together with neuropsychological tests, were used to examine overall brain function and anatomy in three study populations: healthy men at different ages, patients with presumptive Alzheimer's disease, and adults with Down's syndrome. Brain glucose use did not differ with age, whereas an age-related decrement in gray matter volume was found on computed tomographic assessment in healthy subjects. Memory deficits were found to precede significant reductions in brain glucose utilization in mild to moderate Alzheimer's dementia. Furthermore, differences between language and visuoconstructive impairments in patients with mild to moderate Alzheimer's disease were related to hemispheric asymmetry of brain metabolism. Brain glucose utilization was found to be significantly elevated in young adults with Down's syndrome, compared with controls. The importance of establishing strict criteria for selecting control subjects and patients is explained in relation to the findings

  3. Dietary Vitamin D Deficiency in Rats from Middle- to Old-age Leads to Elevated Tyrosine Nitration and Proteomics Changes in Levels of Key Proteins in Brain: Implications for Low Vitamin D-dependent Age-Related Cognitive Decline

    OpenAIRE

    Keeney, Jeriel T. R.; Förster, Sarah; Sultana, Rukhsana; Brewer, Lawrence D.; Caitlin S Latimer; Cai, Jian; Klein, Jon B.; Porter, Nada M.; Butterfield, D. Allan

    2013-01-01

    In addition to the well-known effects of vitamin D (VitD) in maintaining bone health, there is increasing appreciation that this vitamin may serve important roles in other organs and tissues, including the brain. Given that VitD deficiency is especially widespread among the elderly, it is important to understand how the range of serum VitD levels that mimic those found in humans (from low to high) affects the brain during aging from middle-age to old-age. To address this issue, twenty-seven m...

  4. NMDA receptor function, memory, and brain aging

    OpenAIRE

    Newcomer, John W.; Farber, Nuri B.; Olney, John W.

    2000-01-01

    An increasing level of N-methyl-D-aspartate (NMDA) receptor hypofunction within the brain is associated with memory and learning impairments, with psychosis, and ultimately with excitotoxic brain injury. As the brain ages, the NMDA receptor system becomes progressively hypofunctional, contributing to decreases in memory and learning performance. In those individuals destined to develop Alzheimer's disease, other abnormalities (eg, amyloidopathy and oxidative stress) interact to increase the N...

  5. The effects of sex on brain iron status in rats

    Institute of Scientific and Technical Information of China (English)

    HAO Qian; CHANG Yanzhong

    2015-01-01

    Objective:Iron plays essential roles in the human body. Studies have shown that iron is dis-tributed differently in male and female Rats in liver, spleen, bone marrow, kidney, heart. However, the effects of sex on iron distribution in central nervous system are not well established. Methods:To explore the effects of the above mentioned, in this study, female and male Sprague Dawley rats were used at 4 months of age. The synthesis of ferritin light chain (FTL), transferrin receptor1 (TfR1), ferroportin 1 (FPN1), divalent metal transporter 1 ( DMT1) in the cortex, hippocampus, striatum, cerebellum, and olfactory bulb was determined by Western blot a-nalysis. Results:The results showed that the levels of FTL protein in the cortex, hippocampus, striatum, cerebel-lum, and olfactory bulb were higher in female rats than in male rats, but the levels of TfR1 protein were lower in female rats than in male rats. There was no significant change in FPN1 and DMT1 expression in brain. Conclu-sions:These data suggest that sex have effects on brain iron status. Iron is distributed differently in central nervous system in male and female rats. However, the precise mechanisms need further study.

  6. Glutamate (mGluR-5 gene expression in brain regions of streptozotocin induced diabetic rats as a function of age: role in regulation of calcium release from the pancreatic islets in vitro

    Directory of Open Access Journals (Sweden)

    Paulose CS

    2009-11-01

    Full Text Available Abstract Metabotrophic glutamate receptors (mGluRs modulate cellular activities involved in the processes of differentiation and degeneration. In this study, we have analysed the expression pattern of group-I metabotropic glutamate receptor (mGlu-5 in cerebral cortex, corpus striatum, brainstem and hippocampus of streptozotocin induced and insulin treated diabetic rats (D+I as a function of age. Also, the functional role of glutamate receptors in intra cellular calcium release from the pancreatic islets was studied in vitro. The gene expression studies showed that mGlu-5 mRNA in the cerebral cortex increased siginficantly in 7 weeks old diabetic rats whereas decreased expression was observed in brainstem, corpus striatum and hippocampus when compared to control. 90 weeks old diabetic rats showed decreased expression in cerebral cortex, corpus striatum and hippocampus whereas in brainstem the expression increased significantly compared to their respective controls. In 7 weeks old D+I group, mGlu-5 mRNA expression was significantly decreased in cerebral cortex and corpus striatum whereas the expression increased significantly in brainstem and hippocampus. 90 weeks old D+I group showed an increased expression in cerebral cortex, while it was decreased significantly in corpus striatum, brainstem and hippocampus compared to their respective controls. In vitro studies showed that glutamate at lower concentration (10-7 M stimulated calcium release from the pancreatic islets. Our results suggest that mGlu-5 receptors have differential expression in brain regions of diabetes and D+I groups as a function of age. This will have clinical significance in management of degeneration in brain function and memory enhancement through glutamate receptors. Also, the regulatory role of glutamate receptors in calcium release has immense therapeutic application in insulin secretion and function.

  7. Cardiovascular and hemodynamic contribution to brain aging

    NARCIS (Netherlands)

    Sabayan, Behnam

    2014-01-01

    In summary, chapter 1 of this thesis provides a background on the demographic, biologic and cardiovascular aspects of brain aging. Chapter 2 shows that higher blood pressure is associated with lower cognitive decline in very old age. Findings of Chapter 3 indicate that higher blood pressure is assoc

  8. Laser scattering by transcranial rat brain illumination

    Science.gov (United States)

    Sousa, Marcelo V. P.; Prates, Renato; Kato, Ilka T.; Sabino, Caetano P.; Suzuki, Luis C.; Ribeiro, Martha S.; Yoshimura, Elisabeth M.

    2012-06-01

    Due to the great number of applications of Low-Level-Laser-Therapy (LLLT) in Central Nervous System (CNS), the study of light penetration through skull and distribution in the brain becomes extremely important. The aim is to analyze the possibility of precise illumination of deep regions of the rat brain, measure the penetration and distribution of red (λ = 660 nm) and Near Infra-Red (NIR) (λ = 808 nm) diode laser light and compare optical properties of brain structures. The head of the animal (Rattus Novergicus) was epilated and divided by a sagittal cut, 2.3 mm away from mid plane. This section of rat's head was illuminated with red and NIR lasers in points above three anatomical structures: hippocampus, cerebellum and frontal cortex. A high resolution camera, perpendicularly positioned, was used to obtain images of the brain structures. Profiles of scattered intensities in the laser direction were obtained from the images. There is a peak in the scattered light profile corresponding to the skin layer. The bone layer gives rise to a valley in the profile indicating low scattering coefficient, or frontal scattering. Another peak in the region related to the brain is an indication of high scattering coefficient (μs) for this tissue. This work corroborates the use of transcranial LLLT in studies with rats which are subjected to models of CNS diseases. The outcomes of this study point to the possibility of transcranial LLLT in humans for a large number of diseases.

  9. Cognitive functioning of the aging brain

    OpenAIRE

    Tam, Man-kin, Helena; 譚敏堅

    2013-01-01

    This thesis contains two studies which examined the cognitive functioning of the aging brain. Specifically, age-related changes in processing speed and its remediation via cognitive training were studied. In study 1, younger adults (n = 34) and older adults (n = 39) were recruited to investigate the age-related differences in the relationships between processing speed and general cognitive status (GCS). Their performance in GCS (as measured by The Montreal Cognitive Assessment, Hong Kong Vers...

  10. Metabolic drift in the aging brain.

    Science.gov (United States)

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

    2016-05-01

    Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication. PMID:27182841

  11. Susceptibility to calcium dysregulation during brain aging

    Directory of Open Access Journals (Sweden)

    Ashok Kumar

    2009-11-01

    Full Text Available Calcium (Ca2+ is a highly versatile intracellular signaling molecule that is essential for regulating a variety of cellular and physiological processes ranging from fertilization to programmed cell death. Research has provided ample evidence that brain aging is associated with altered Ca2+ homeostasis. Much of the work has focused on the hippocampus, a brain region critically involved in learning and memory, which is particularly susceptible to dysfunction during senescence. The current review takes a broader perspective, assessing age-related changes in Ca2+ sources, Ca2+ sequestration, and Ca2+ binding proteins throughout the nervous system. The nature of altered Ca2+ homeostasis is cell specific and may represent a deficit or a compensatory mechanism, producing complex patterns of impaired cellular function. Incorporating the knowledge of the complexity of age-related alterations in Ca2+ homeostasis will positively shape the development of highly effective therapeutics to treat brain disorders.

  12. Light-sensitive brain pathways and aging.

    Science.gov (United States)

    Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

    2016-03-15

    Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

  13. Rat brain methotrexate levels following cranial irradiation

    International Nuclear Information System (INIS)

    Brain disfunction has been reported in leukemia patients receiving both brain irradiation and methotrexate (MTX) therapy. It has been speculated that the neuropathy is a result of radiation-induced vascular permeability in the brain, allowing increased levels of MTX to cross the Blood-Brain-Barrier. If this hypothesis is correct, it may be possible to reduce brain MTX concentrations following irradiation by administering drugs which reduce the radiation-induced vascular permeability. To examine the hypothesis, the authors have irradiated male S-D rats to the brain area only with a single dose of 20 Gy /sup 137/Cs gamma rays. Various times following irradiation we have administered MTX i.v. at either 50 or 100 mg/kg. At 18 hours after MTX administration, brain tissue was taken, and the MTX concentration was measured. Compared to nonirradiated controls, elevated levels of MTX were seen in the brain when the drug was administered 30 hours following irradiation (p < 0.05). Elevated levels were not seen when the drug was administered 7 or 14 days post irradiation. Blood levels of the drug in irradiated animals were elevated compared to nonirradiated controls when MTX was administered 7 days post irradiation. Additional time points must be evaluated before any substantial conclusions can be drawn

  14. Cognitive dysfunction and histological findings in adult rats one year after whole brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Akiyama, Katsuhiko; Tanaka, Ryuichi; Sato, Mitsuya; Takeda, Norio [Niigata Univ. (Japan). Brain Research Inst.

    2001-12-01

    Cognitive dysfunction and histological changes in the brain were investigated following irradiation in 20 Fischer 344 rats aged 6 months treated with whole brain irradiation (WBR) (25 Gy/single dose), and compared with the same number of sham-irradiated rats as controls. Performance of the Morris water maze task and the passive avoidance task were examined one year after WBR. Finally, histological and immunohistochemical examinations using antibodies to myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and neurofilament (NF) were performed of the rat brains. The irradiated rats continued to gain weight 7 months after WBR whereas the control rats stopped gaining weight. Cognitive functions in both the water maze task and the passive avoidance task were lower in the irradiated rats than in the control rats. Brain damage consisting of demyelination only or with necrosis was found mainly in the body of the corpus callosum and the parietal white matter near the corpus callosum in the irradiated rats. Immunohistochemical examination of the brains without necrosis found MBP-positive fibers were markedly decreased in the affected areas by irradiation; NF-positive fibers were moderately decreased and irregularly dispersed in various shapes in the affected areas; and GFAP-positive fibers were increased, with gliosis in those areas. These findings are similar to those in clinically accelerated brain aging in conditions such as Alzheimer's disease, Binswanger's disease, and multiple sclerosis. (author)

  15. Aquaporin 9 in rat brain after severe traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hui Liu

    2012-03-01

    Full Text Available OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9 in rat brain, after severe traumatic brain injury (TBI. METHODS: Brain water content (BWC, tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC, immunofluorescence (IF, western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest peaks at 6 and 72 hours, and the blood brain barrier (BBB was severely destroyed at six hours after the TBI. The worst brain ischemia occurred at 72 hours after TBI. Widespread AQP9-positive astrocytes and neurons in the hypothalamus were detected by means of IHC and IF after TBI. The abundance of AQP9 and its mRNA increased after TBI and reached two peaks at 6 and 72 hours, respectively, after TBI. CONCLUSIONS: Increased AQP9 might contribute to clearance of excess water and lactate in the early stage of TBI. Widespread AQP9-positive astrocytes might help lactate move into neurons and result in cellular brain edema in the later stage of TBI. AQP9-positive neurons suggest that AQP9 plays a role in energy balance after TBI.

  16. The Impact of Traumatic Brain Injury on the Aging Brain.

    Science.gov (United States)

    Young, Jacob S; Hobbs, Jonathan G; Bailes, Julian E

    2016-09-01

    Traumatic brain injury (TBI) has come to the forefront of both the scientific and popular culture. Specifically, sports-related concussions or mild TBI (mTBI) has become the center of scientific scrutiny with a large amount of research focusing on the long-term sequela of this type of injury. As the populace continues to age, the impact of TBI on the aging brain will become clearer. Currently, reports have come to light that link TBI to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as certain psychiatric diseases. Whether these associations are causations, however, is yet to be determined. Other long-term sequelae, such as chronic traumatic encephalopathy (CTE), appear to be associated with repetitive injuries. Going forward, as we gain better understanding of the pathophysiological process involved in TBI and subclinical head traumas, and individual traits that influence susceptibility to neurocognitive diseases, a clearer, more comprehensive understanding of the connection between brain injury and resultant disease processes in the aging brain will become evident. PMID:27432348

  17. Functional interrelationship of brain aging and delirium.

    Science.gov (United States)

    Rapazzini, Piero

    2016-02-01

    Theories on the development of delirium are complementary rather than competing and they may relate to each other. Here, we highlight that similar alterations in functional brain connectivity underlie both the observed age-related deficits and episodes of delirium. The default mode network (DMN) is a group of brain regions showing a greater level of activity at rest than during attention-based tasks. These regions include the posteromedial-anteromedial cortices and temporoparietal junctions. Evidence suggests that awareness is subserved through higher order neurons associated with the DMN. By using functional MRI disruption of DMN, connectivity and weaker task-induced deactivations of these regions are observed both in age-related cognitive impairment and during episodes of delirium. We can assume that an acute up-regulation of inhibitory tone within the brain acts to further disrupt network connectivity in vulnerable patients, who are predisposed by a reduced baseline connectivity, and triggers the delirium.

  18. Brain plasticity, memory, and aging: a discussion

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, E.L.; Rosenzweig, M.R.

    1977-12-01

    It is generally assumed that memory faculties decline with age. A discussion of the relationship of memory and aging and the possibility of retarding the potential decline is hampered by the fact that no satisfactory explanation of memory is available in either molecular or anatomical terms. However, this lack of description of memory does not mean that there is a lack of suggested mechanisms for long-term memory storage. Present theories of memory usually include first, neurophysiological or electrical events, followed by a series of chemical events which ultimately lead to long-lasting anatomical changes in the brain. Evidence is increasing for the biochemical and anatomical plasticity of the nervous system and its importance in the normal functioning of the brain. Modification of this plasticity may be an important factor in senescence. This discussion reports experiments which indicate that protein synthesis and anatomical changes may be involved in long-term memory storage. Environmental influences can produce quantitative differences in brain anatomy and in behavior. In experimental animals, enriched environments lead to more complex anatomical patterns than do colony or impoverished environments. This raises fundamental questions about the adequacy of the isolated animal which is frequently being used as a model for aging research. A more important applied question is the role of social and intellectual stimulation in influencing aging of the human brain.

  19. Sirtuins: from Metabolic Regulation to Brain Aging

    Directory of Open Access Journals (Sweden)

    Wenzhen eDuan

    2013-07-01

    Full Text Available Brain aging is characterized by progressive loss of neurophysiological functions that is often accompanied by age-associated neurodegeneration. Calorie restriction has been linked to extension of lifespan and reduction of the risk of neurodegenerative diseases in experimental model systems. Several signaling pathways have been indicated to underlie the beneficial effects of calorie restriction, among which the sirtuin family has been suggested to play a central role. In mammals, it has been established that sirtuins regulate physiological responses to metabolism and stress, two key factors that affect the process of aging. Sirtuins represent a promising new class of conserved deacetylases that play an important role in regulating metabolism and aging. This review focuses on current understanding of the relation between metabolic pathways involving sirtuins and the brain aging process, with focus on SIRT1 and SIRT3. Identification of therapeutic agents capable of modulating the expression and/or activity of sirtuins is expected to provide promising strategies for ameliorating neurodegeneration. Future investigations regarding the concerted interplay of the different sirtuins will help us understand more about the aging process, and potentially lead to the development of therapeutic approaches for the treatment of age-related neurodegenerative diseases and promotion of successful aging.

  20. Immunochemical characterization of rat brain protein kinase

    International Nuclear Information System (INIS)

    Polyclonal antibodies against rat brain protein kinase C (the Ca2+/phospholipid-dependent enzyme) were raised in goat. These antibodies can neutralize completely the kinase activity in purified enzyme preparation as well as that in the crude homogenate. Immunoblot analysis of the purified and the crude protein kinase C preparations revealed a major immunoreactive band of 80 kDa. The antibodies also recognize the same enzyme from other rat tissues. Neuronal tissues (cerebral cortex, cerebellum, hypothalamus, and retina) and lymphoid organs (thymus and spleen) were found to be enriched in protein kinase C, whereas lung, kidney, liver, heart, and skeletal muscle contained relatively low amounts of this kinase. Limited proteolysis of the purified rat brain protein kinase C with trypsin results in an initial degradation of the kinase into two major fragments of 48 and 38 kDa. Both fragments are recognized by the antibodies. However, further digestion of the 48-kDa fragment to 45 kDa and the 38-kDa fragment to 33 kDa causes a loss of the immunoreactivity. Upon incubation of the cerebellar extract with Ca2+, the 48-kDa fragment was also identified as a major proteolytic product of protein kinase C. Proteolytic degradation of protein kinase C converts the Ca2+/phospholipid-dependent kinase to an independent form without causing a large impairment of the binding of [3H]phorbol 12,13-dibutyrate. The two major proteolytic fragments were separated by ion exchange chromatography and one of them (45-48 kDa) was identified as a protein kinase and the other (33-38 kDa) as a phorbol ester-binding protein. These results demonstrate that rat brain protein kinase C is composed of two functionally distinct units, namely, a protein kinase and a Ca2+-independent/phospholipid-dependent phorbol ester-binding protein

  1. Age- and brain-region-specific effects of dietary vitamin K on myelin sulfatides

    OpenAIRE

    Crivello, Natalia A.; Casseus, Sherley L.; Peterson, James W.; Smith, Donald E.; Sarah L. Booth

    2010-01-01

    Dysregulation of myelin sulfatides is a risk factor for cognitive decline with age. Vitamin K is present in high concentrations in the brain and has been implicated in the regulation of sulfatide metabolism. Our objective was to investigate the age-related interrelation between dietary vitamin K and sulfatides in myelin fractions isolated from the brain regions of Fischer 344 male rats fed one of two dietary forms of vitamin K: phylloquinone or its hydrogenated form, dihydrophylloquinone for ...

  2. 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. PMID:26364584

  3. Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model.

    Science.gov (United States)

    Aydın, A Fatih; Çoban, Jale; Doğan-Ekici, Işın; Betül-Kalaz, Esra; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2016-04-01

    D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; β-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5% w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats. PMID:26518192

  4. “脑功复得”改善脑老化的基础研究%xperimental study on the effect of Naogongfude on the aging of the rat brain

    Institute of Scientific and Technical Information of China (English)

    何小川; 蔡文琴; 李泽桂; 杨忠

    2001-01-01

    Objective To evaluate the effect of Naogongfude (NGFD, a traditional Chinese medicine orally administrated) on learning and memory and the expressions of synaptophysin (SY) and Tau-protein in cerebral cortex and hippocampus in aged rats and to explore the possible mechanism. Methods Rats were divided into normal and neural disturbance groups according to the outcomes of active avoidance reaction (AAR) test, and then each group was randomly divided into control and NGFD-treated experimental groups. Animals were orally fed with NGFD for 2 months (5 ml/d) in experimental group or routinely fed in control and taken AAR and passive avoidance reaction (PAR) tests. After the rats were sacrificed, the synaptosome count, the expression of SY and Tau-protein, and the neuron apoptosis in cerebrum were examined. Results The rats after 2-month NGFD administration had an increased AAR acquisition, obviously delayed AAR extinction and prolonged step through latency (STL) of PAR. The number of synaptosomes was raised and the immunoreactive intensity of synaptophysin was increased remarkedly, while Tau-protein immunoreactivity and apoptotic cells were decreased in cerebrum. Conclusion NGFD does have the effect of improving brain function and putting off the aging of rat brain according to the results of behavior study and morphological observation.%目的 研究中药合剂 “脑功复得”口服液(以下简称脑功复得)对老龄大鼠学习记忆能力及大脑皮质海马突触泡膜素(Synaptophysin, SY)、Tau-蛋白表达等的影响,探讨其延缓脑老化的功效及可能机制。方法 应用爬杆主动回避反应(Active avoidance reaction,AAR)将动物分为学习记忆正常组和障碍组,再随机分别设置对照组(普食)和实验喂药组(5 ml/d,2月)。在此基础上进行AAR和多功能箱被动回避反应(Passive avoidance reaction,PAR)训练、突触体计数、突触泡膜素和Tau蛋白免疫组化染色

  5. 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.

  6. Aged rats are hypo-responsive to acute restraint: implications for psychosocial stress in aging

    Directory of Open Access Journals (Sweden)

    Heather M Buechel

    2014-02-01

    Full Text Available Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/ stress hormone/ allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation, and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events. However, the mechanistic underpinnings of this age-related shift in chronic psychosocial stress response, or the initial acute phase of that chronic response, have been less well-studied. Here, we separated young (3 mo. and aged (21 mo. male F344 rats into control and acute restraint (an animal model of psychosocial stress groups (n = 9-12/ group. We then assessed hippocampus-associated behavioral, electrophysiological, and transcriptional outcomes, as well as blood glucocorticoid and sleep architecture changes. Aged rats showed characteristic water maze, deep sleep, transcriptome, and synaptic sensitivity changes compared to young. Young and aged rats showed similar levels of distress during the three hour restraint, as well as highly significant increases in blood glucocorticoid levels 21 hours after restraint. However, young, but not aged, animals responded to stress exposure with water maze deficits, loss of deep sleep and hyperthermia. These results demonstrate that aged subjects are hypo-responsive to new-onset acute psychosocial stress, which may have negative consequences for long-term stress adaptation and suggest that age itself may act as a stressor occluding the influence of new onset stressors.

  7. Aged rats are hypo-responsive to acute restraint: implications for psychosocial stress in aging.

    Science.gov (United States)

    Buechel, Heather M; Popovic, Jelena; Staggs, Kendra; Anderson, Katie L; Thibault, Olivier; Blalock, Eric M

    2014-01-01

    Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/stress hormone/allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation), and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events. However, the mechanistic underpinnings of this age-related shift in chronic psychosocial stress response, or the initial acute phase of that chronic response, have been less well-studied. Here, we separated young (3 month) and aged (21 month) male F344 rats into control and acute restraint (an animal model of psychosocial stress) groups (n = 9-12/group). We then assessed hippocampus-associated behavioral, electrophysiological, and transcriptional outcomes, as well as blood glucocorticoid and sleep architecture changes. Aged rats showed characteristic water maze, deep sleep, transcriptome, and synaptic sensitivity changes compared to young. Young and aged rats showed similar levels of distress during the 3 h restraint, as well as highly significant increases in blood glucocorticoid levels 21 h after restraint. However, young, but not aged, animals responded to stress exposure with water maze deficits, loss of deep sleep and hyperthermia. These results demonstrate that aged subjects are hypo-responsive to new-onset acute psychosocial stress, which may have negative consequences for long-term stress adaptation and suggest that age itself may act as a stressor occluding the influence of new onset stressors.

  8. Poststroke Cell Therapy of the Aged Brain

    Directory of Open Access Journals (Sweden)

    Aurel Popa-Wagner

    2015-01-01

    Full Text Available During aging, many neurodegenerative disorders are associated with reduced neurogenesis and a decline in the proliferation of stem/progenitor cells. The development of the stem cell (SC, the regenerative therapy field, gained tremendous expectations in the diseases that suffer from the lack of treatment options. Stem cell based therapy is a promising approach to promote neuroregeneration after brain injury and can be potentiated when combined with supportive pharmacological drug treatment, especially in the aged. However, the mechanism of action for a particular grafted cell type, the optimal delivery route, doses, or time window of administration after lesion is still under debate. Today, it is proved that these protections are most likely due to modulatory mechanisms rather than the expected cell replacement. Our group proved that important differences appear in the aged brain compared with young one, that is, the accelerated progression of ischemic area, or the delayed initiation of neurological recovery. In this light, these age-related aspects should be carefully evaluated in the clinical translation of neurorestorative therapies. This review is focused on the current perspectives and suitable sources of stem cells (SCs, mechanisms of action, and the most efficient delivery routes in neurorestoration therapies in the poststroke aged environment.

  9. Relationship between aged-rat brain fatty acid composition and fatty acid beta-oxidation%老年大鼠脑脂肪酸含量与脂肪酸β-氧化的关系

    Institute of Scientific and Technical Information of China (English)

    杨磊; 石如玲; 张煜; 赵春澎; 付云; 黄艳梅

    2011-01-01

    目的 比较老年及青年大鼠脑脂肪酸含量、肝脏脂肪酸β-氧化关键酶表达水平的不同,探讨衰老时脂肪酸含量的变化与脂肪酸β-氧化功能的关系.方法 老年组和青年组大鼠各10只,用气相色谱法分析脑皮质脂肪酸含量,用反转录聚合酶链反应(RT-PCR)方法测定过氧化物酶体β-氧化关键酶脂酰辅酶A氧化酶(AOX1)、线粒体β-氧化关键酶肉碱脂酰转移酶1( CPT1)及过氧化物酶体增殖剂激活受体α(PPARα) mRNA的表达水平,用游离脂肪酸试剂盒测定血清游离脂肪酸(FFA)含量.结果 与青年组相比,老年组大鼠脑内C18∶0、C20∶4、C22∶6含量降低(P<0.05或P<0.01),脑内C16∶1、C18∶1、C20∶0、C20∶1、C22∶1、C24∶0、C24∶1含量升高(P<0.05或P<0.01),肝脏AOX1、CPT1、PPARα mRNA水平降低(P<0.05),血清总FFA含量降低(P<0.05).结论 衰老时大鼠脑脂肪酸含量变化的原因可能由线粒体和过氧化物酶体β-氧化功能降低所致.%Objective To analyze the differences of brain fatty acid content and liver fatty acid beta-oxidation enzyme expression between aged and young rats, and to explore the relationship between aged brain fatty acid composition and fatty acid beta-oxidation. Methods Old (22 months) and young (3 months) male rats were used in this experiment. Every ten mice in old group and young group. Fatty acid composition and contents of cerebral cortex were detected by gas chromatography analysis. The mRNA levels of acyl-CoA oxidase 1 (AOX1) ,camitine palmitoyltransferase 1 (CPT1) and peroxisome proliferator-ac-tivated receptor-a (PPARa) in liver were detected by reverse transcription-polymerase chain reaction (RT-PCR). Serum free fatty acid (FFA) level was measured by the assay kit. Results Compared with the young group, C18 : 0.C20 : 4 and C22 : 6 levels decreased( P<0.05 or P<0.01), while C16 : 1.C18 : l,C20 :0,C20 : 1,C22 : 1,C24 : 0 and C24 : 1 levels increased (P< 0.05 orP<0

  10. Executive dysfunction, brain aging, and political leadership.

    Science.gov (United States)

    Fisher, Mark; Franklin, David L; Post, Jerrold M

    2014-01-01

    Decision-making is an essential component of executive function, and a critical skill of political leadership. Neuroanatomic localization studies have established the prefrontal cortex as the critical brain site for executive function. In addition to the prefrontal cortex, white matter tracts as well as subcortical brain structures are crucial for optimal executive function. Executive function shows a significant decline beginning at age 60, and this is associated with age-related atrophy of prefrontal cortex, cerebral white matter disease, and cerebral microbleeds. Notably, age-related decline in executive function appears to be a relatively selective cognitive deterioration, generally sparing language and memory function. While an individual may appear to be functioning normally with regard to relatively obvious cognitive functions such as language and memory, that same individual may lack the capacity to integrate these cognitive functions to achieve normal decision-making. From a historical perspective, global decline in cognitive function of political leaders has been alternatively described as a catastrophic event, a slowly progressive deterioration, or a relatively episodic phenomenon. Selective loss of executive function in political leaders is less appreciated, but increased utilization of highly sensitive brain imaging techniques will likely bring greater appreciation to this phenomenon. Former Israeli Prime Minister Ariel Sharon was an example of a political leader with a well-described neurodegenerative condition (cerebral amyloid angiopathy) that creates a neuropathological substrate for executive dysfunction. Based on the known neuroanatomical and neuropathological changes that occur with aging, we should probably assume that a significant proportion of political leaders over the age of 65 have impairment of executive function. PMID:25901887

  11. Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

    Science.gov (United States)

    Banerjee, S; Poddar, M K

    2016-04-01

    Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity. PMID:26808776

  12. Lithium: modification of behavioral activity and brain biogenic amines in developing hyperthyroid rats.

    Science.gov (United States)

    Rastoge, R B; Singhal, R L

    1977-04-01

    Daily treatment of neonatal rats with 1-triiodothyronine for 30 days increased locomotor activity as well as the synthesis and presumably, release of brain norepinephrine, dopamine and 5-hydroxytryptamine. Whereas administration of lithium carbonate (60 mg/kg) to normal rats for 10 days, beginning from the 20th day of age, produced no significant effect, this antimanic drug significantly decreased the observed increase in spontaneous locomotor activity in l-triiodothyronine-treated rats. Lithium treatment in normal rats increased the activity of striatal tyrosine hydroxylase, but produced no significant effect on the endogenous levels of norepinephrine and dopamine in several discrete brain regions examined. Lithium, enhanced deamination of catecholamines as evidenced by increased level of 3,4-dihydroxyphenylacetic acid and monoamine oxidase activity in normal rats. The activity of catechol o-methyltransferase was decreased to 82 and 59% in midbrain and crebral cortex of normal rats, respectively. Furthermore, chronic treatment with lithium increased endogenous levels of tryptophan, tryptophan hydroxylase, 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, in normal animals. In contrast to the effects seen in normal rats, admininstration of lithium in l-triiodothyronine-treated animals significantly decreased tyrosine hydroxylase as well as dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid, suggesting that this antimanic drug reduced the synthesis and turnover of dopamine. However, the steady-state levels of norepinephrine were raised in hypothalamus, pons-medulla, midbrain and striatum of lithium-treated hyperthyroid rats. As seen in normal animals, lithium in l-triidothyronine-treated rats increased trytophan, tryptophan hydroxylase and 5-hydroxytryptamine levels, but decreased the concentration of 5-hydroxyindoleacetic acid. The results show that the suppressed behavioral activity seen in lithium-treated hyperthyroid rats may be

  13. The quantitative analysis of S100 in the brain tissue and serum following diffuse brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Wang Qi; Huang Ping; Xing Bo; Tuo Ya; Zhang Yongpan; Tian Weiping; Wang Zhenyuan

    2007-01-01

    Objective To investigate the dynamics of the level of S100 in cerebrum, brainstem, and serum following the diffuse brain injury in rats and provide the experimental evidences for estimating injury time. Methods ELISA was used to determine whether S100 protein is changed after diffuse brain injury in rats. Forty rats were sacrificed at 0.5 hour, 2 hours, 4 hours, 12 hours, 24 hours, 3 d and 7 d after diffuse brain injury and normal rats as control. Results The level of S100 in cerebrum, brainstem, and serum increased, followed by a decrease, and then further increased. The level of S100 could be detected to increase at 30 minutes and reached the peak at 4 hours after DBI. The level decreased gradually to the normal at 1d and till 3 d formed the second peak. The level returned to the normal at 7d following injury again. In the postmortem injury groups, there were no significant changes compared to the control group. Conclusion The present study showed that the time-dependent expression of S100 is obvious following diffuse brain injury in rats and suggested that S100 will be a suitable marker for diffuse brain injury age determination.

  14. Brain mitochondrial dysfunction in aging, neurodegeneration and Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Ana Navarro

    2010-09-01

    Full Text Available Brain senescence and neurodegeneration occur with a mitochondrial dysfunction characterized by impaired electron transfer and by oxidative damage. Brain mitochondria of old animals show decreased rates of electron transfer in complexes I and IV, decreased membrane potential, increased content of the oxidation products of phospholipids and proteins and increased size and fragility. This impairment, with complex I inactivation and oxidative damage, is named “complex I syndrome” and is recognized as characteristic of mammalian brain aging and of neurodegenerative diseases. Mitochondrial dysfunction is more marked in brain areas as rat hippocampus and frontal cortex, in human cortex in Parkinson’s disease and dementia with Lewy bodies, and in substantia nigra in Parkinson’s disease. The molecular mechanisms involved in complex I inactivation include the synergistic inactivations produced by ONOO- mediated reactions, by reactions with free radical intermediates of lipid peroxidation and by amine-aldehyde adduction reactions. The accumulation of oxidation products prompts the idea of antioxidant therapies. High doses of vitamin E produce a significant protection of complex I activity and mitochondrial function in rats and mice, and with improvement of neurological functions and increased median life span in mice. Mitochondria-targeted antioxidants, as the Skulachev cations covalently attached to vitamin E, ubiquinone and PBN and the SS tetrapeptides, are negatively charged and accumulate in mitochondria where they exert their antioxidant effects. Activation of the cellular mechanisms that regulate mitochondrial biogenesis is another potential therapeutic strategy, since the process generates organelles devoid of oxidation products and with full enzymatic activity and capacity for ATP production.

  15. Age-related differences in the toxicity of ochratoxin A in female rats.

    Science.gov (United States)

    Dortant, P M; Peters-Volleberg, G W; Van Loveren, H; Marquardt, R R; Speijers, G J

    2001-01-01

    Ochratoxin A (OTA) is a mycotoxin found in food and feedstuffs of plant and animal origin. OTA exposure is related to nephropathy in humans. Age-related differences, especially in nephro- and immunotoxicity of OTA, were investigated in young adult (aged 12 weeks) and old (aged 27-30 months) female SPF Wag rats, treated by gavage with 0, 0.07, 0.34 or 1.68 mg OTA/kg body weight for 4 weeks. In both age groups, survival was significantly decreased in the highest dose group. Clinical condition, body weight, clinical chemistry parameters (ALAT, ASAT, creatinin and urea) and target organs (as identified by weight and pathology - kidney, liver, adrenals, forestomach and brain) were affected by age and dose, but often more severely in old than in young rats. OTA induced primarily nephropathy. Old rats were more sensitive to induction of tubular karyomegaly and vacuolation/necrosis. In young rats, OTA induced a dose-related thickening of the basement membrane and reduction in splenic T-cell fraction. Decreased IgG levels were seen at 0.34 mg/kg OTA (young and old rats) and 1.68 mg/kg OTA (young rats). Vacuolation of the white brain matter (cerebellar medulla and ventral parts of the brain stem) was significantly increased in young rats at 0.34 and 1.68 mg/kg OTA and in old rats at 0.07 and 0.34 mg/kg OTA. It was concluded that: (1) the profiles of OTA toxicity for both age groups are similar, with the kidney and possibly the brain being primary target organs; (2) based on clinical and pathological data old rats are more sensitive to OTA than young rats; and (3) the immune system is probably not the primary target of OTA toxicity.

  16. Moxibustion on Telomerase Activity in Aging Rat

    Institute of Scientific and Technical Information of China (English)

    WU Huan-gan; GUO Lan-qin; CHEN Han-ping; SUN Guo-jie; ZHANG Wei; SHI Yin; ZHANG Qiu-juan; LIU Hui-rong

    2007-01-01

    Objective: To investigate the effect of moxibustion on telomerase activity and genes expression in tissues of senescent rats. Methods: Subacute aging rats model were established by injection with D-gal solution. Points Shenshu (BL 23) were treated with moxibustion in treatment group, contrasting with a model group and a normal group. Enzyme-Linked Immunosorbent Assays(ELISA) was used for the level oftelomerase activity in liver tissues, and In Situ Hybridization(ISH) was used for the condition of expression of telomerase genes in liver tissues. Results: The level of telomerase activity in the aging model group was obviously lower than that in normal control group (P<0.01), the level in moxibustion group was obviously higher than that in model group(P<0.05). In comparison with normal rats, the positive-expressed areas and photodensity of telomerase genes in aging model group were all significantly lower (P<0.01,P<0.01), and the positive-expressed areas in moxibustion group was significantly higher than that in model group (P<0.01). Conclusions: Moxibustion could regulate telomerase activity of senile rats, hence delaying aging.

  17. Propofol Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats.

    Science.gov (United States)

    Shi, Song-sheng; Zhang, Hua-bin; Wang, Chun-hua; Yang, Wei-zhong; Liang, Ri-sheng; Chen, Ye; Tu, Xian-kun

    2015-12-01

    Our previous studies demonstrated that propofol protects rat brain against focal cerebral ischemia. However, whether propofol attenuates early brain injury after subarachnoid hemorrhage in rats remains unknown until now. The present study was performed to evaluate the effect of propofol on early brain injury after subarachnoid hemorrhage in rats and further explore the potential mechanisms. Sprague-Dawley rats underwent subarachnoid hemorrhage (SAH) by endovascular perforation then received treatment with propofol (10 or 50 mg/kg) or vehicle after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and malondialdehyde (MDA) content were measured 24 h after SAH. Expression of nuclear factor erythroid-related factor 2 (Nrf2), nuclear factor-kappa B (NF-κB) p65, and aquaporin 4 (AQP4) expression in rat brain were detected by Western blot. Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) were determined by reverse transcription-polymerase chain reaction (RT-PCR). Expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were assessed by ELISA. Neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and MDA content were significantly reduced by propofol. Furthermore, expression of Nrf2 in rat brain was upregulated by propofol, and expression of NF-κB p65, AQP4, COX-2, MMP-9, TNF-α, and IL-1β in rat brain were attenuated by propofol. Our results demonstrated that propofol improves neurological scores, reduces brain edema, blood-brain barrier (BBB) permeability, inflammatory reaction, and lipid peroxidation in rats of SAH. Propofol exerts neuroprotection against SAH-induced early brain injury, which might be associated with the inhibition of inflammation and lipid peroxidation. PMID:26342279

  18. Exercise and the Aging Brain. (The 1982 C. H. McCloy Research Lecture)

    Science.gov (United States)

    Spirduso, Waneen W.

    1983-01-01

    Exercise may postpone the deterioration in response speed that generally appears in the motor system of the aging by maintaining the nigrostriatal dopaminergic system in the brain. Exercise may also ameliorate symptoms of Parkinson's disease. Results of laboratory studies involving animals and rats are reported. (Author/PP)

  19. Brain Aging in the Oldest-Old

    Directory of Open Access Journals (Sweden)

    A. von Gunten

    2010-01-01

    Full Text Available Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimer's disease (AD decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. Brain aging is characterised by the formation of neurofibrillary tangles (NFTs and senile plaques (SPs as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions

  20. Congenital viral infections of the brain: lessons learned from lymphocytic choriomeningitis virus in the neonatal rat.

    Directory of Open Access Journals (Sweden)

    Daniel J Bonthius

    2007-11-01

    Full Text Available The fetal brain is highly vulnerable to teratogens, including many infectious agents. As a consequence of prenatal infection, many children suffer severe and permanent brain injury and dysfunction. Because most animal models of congenital brain infection do not strongly mirror human disease, the models are highly limited in their abilities to shed light on the pathogenesis of these diseases. The animal model for congenital lymphocytic choriomeningitis virus (LCMV infection, however, does not suffer from this limitation. LCMV is a well-known human pathogen. When the infection occurs during pregnancy, the virus can infect the fetus, and the developing brain is particularly vulnerable. Children with congenital LCMV infection often have substantial neurological deficits. The neonatal rat inoculated with LCMV is a superb model system of human congenital LCMV infection. Virtually all of the neuropathologic changes observed in humans congenitally infected with LCMV, including microencephaly, encephalomalacia, chorioretinitis, porencephalic cysts, neuronal migration disturbances, periventricular infection, and cerebellar hypoplasia, are reproduced in the rat model. Within the developing rat brain, LCMV selectively targets mitotically active neuronal precursors. Thus, the targets of infection and sites of pathology depend on host age at the time of infection. The rat model has further shown that the pathogenic changes induced by LCMV infection are both virus-mediated and immune-mediated. Furthermore, different brain regions simultaneously infected with LCMV can undergo widely different pathologic changes, reflecting different brain region-virus-immune system interactions. Because the neonatal rat inoculated with LCMV so faithfully reproduces the diverse neuropathology observed in the human counterpart, the rat model system is a highly valuable tool for the study of congenital LCMV infection and of all prenatal brain infections In addition, because LCMV

  1. Social support, stress and the aging brain.

    Science.gov (United States)

    Sherman, Stephanie M; Cheng, Yen-Pi; Fingerman, Karen L; Schnyer, David M

    2016-07-01

    Social support benefits health and well-being in older individuals, however the mechanism remains poorly understood. One proposal, the stress-buffering hypothesis states social support 'buffers' the effects of stress on health. Alternatively, the main effect hypothesis suggests social support independently promotes health. We examined the combined association of social support and stress on the aging brain. Forty healthy older adults completed stress questionnaires, a social network interview and structural MRI to investigate the amygdala-medial prefrontal cortex circuitry, which is implicated in social and emotional processing and negatively affected by stress. Social support was positively correlated with right medial prefrontal cortical thickness while amygdala volume was negatively associated with social support and positively related to stress. We examined whether the association between social support and amygdala volume varied across stress level. Stress and social support uniquely contribute to amygdala volume, which is consistent with the health benefits of social support being independent of stress. PMID:26060327

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

    Science.gov (United States)

    Cape, Ronald D. T.

    1989-01-01

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

  3. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

    Directory of Open Access Journals (Sweden)

    Huang Yen

    2011-09-01

    Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

  4. Correlation of brain-derived neurotrophic factor to cognitive impairment following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Dezhi Kang; Zhang Guo

    2008-01-01

    BACKGROUND: In vitro and in vivo studies have confirmed that brain-derived neurotrophic factor (BDNF) can promote survival and differentiation of cholinergic, dopaminergic and motor neurons, and axonal regeneration. BDNF has neuroprotective effects on the nervous system. OBJECTIVE: To explore changes in BDNF expression and cognitive function in rats after brain injury DESIGN, TIME AND SETTING: The neuropathology experiment was performed at the Second Research Room, Department of Neurosurgery, Fujian Medical University (China) from July 2007 to July 2008. MATERIALS: A total of 72 healthy, male, Sprague Dawley, rats were selected for this study. METHODS: Rat models of mild and moderate traumatic brain injury were created by percussion, according to Feeney's method (n = 24, each group). A bone window was made in rats from the sham operation group (n = 24), but no attack was conducted. MAIN OUTCOME MEASURES: At days 1,2, 4 and 7 following injury, BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was examined by immunohistochemistry (streptavidin-biotin-peroxidase complex method). Changes in rat cognitive function were assessed by the walking test, balance-beam test and memory function detection. RESULTS: Cognitive impairment was aggravated at day 2, and recovered to normal at days 3 and 7 in rats from the mild and moderate traumatic brain injury groups. BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was increased at 1 day, decreased at day 2, and then gradually increased in the mild and moderate traumatic brain injury groups. BDNF expression was greater in rats from the moderate traumatic brain injury group than in the sham operation and mild traumatic brain injury groups (P < 0.05). CONCLUSION: BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain is correlated to cognitive impairment after traumatic brain injury. BDNF has a protective effect on cognitive function in rats

  5. Effects of smoking on brain aging, 1

    International Nuclear Information System (INIS)

    The chronic effects of smoking on regional cerebral blood flow (CBF), and on serum lipids and lipoprotein levels in neurologically normal subjects from 25 to 85 years old were studied. CBF was studied by the 133-Xenon inhalation method and gray matter flow was calculated following the method of Obrist et al. A hundred and twentyfive subjects who had no abnormalities in neurological examinations nor in CT scan, were divided into two groups smokers (48) and non-smokers (77). Those who had a smoking index (Number of cigarettes/day) x (years of smoking history)>200 were designated as smokers. The mean smoking index of smokers was 697. sixty-five of the 77 subjects in the non-smoking group had never smoked, and the mean smoking index of non-smokers was 16. Increased reduction of CBF with advancing age was clearly observed. In the male, CBF was significantly lower in smokers than in non-smokers (mean CBF 15% lower in smokers, p<0.001). Compared to non-smokers, CBF in smokers was found to be significantly lower than the expected age matched value. Serum high density lipoprotein cholesterol values in smokers were significantly lower, and total cholesterol levels significantly higher than in non-smokers. We concluded that smoking chronically reduced CBF. Age dependent decrease of CBF was deteriorated by chronic smoking. Then, chronic smoking was suggested to be a risk factor for brain aging. Decrease of CBF in smokers was probably due to advanced atherosclerosis which produces vascular narrowing and raised resistance in cerebral blood vessels. (author)

  6. Brain dysfunctions in Wistar rats exposed to municipal landfill leachates

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    Chibuisi G. Alimba

    2015-12-01

    Full Text Available Brain damage induced by Olusosun and Aba-Eku municipal landfill leachates was investigated in Wistar rats. Male rats were orally exposed to 1–25% concentrations of the leachates for 30 days. Catalase (CAT and superoxide dismutase (SOD activities, and malondialdehyde (MDA concentrations in the brain and serum of rats were evaluated; body and brain weight gain and histopathology were examined. There was significant (p < 0.05 decrease in body weight gain and SOD activity but increase in absolute and relative brain weight gain, MDA concentration and CAT activity in both brain and serum of treated rats. The biochemical parameters, which were more altered in the brain than serum, corroborated the neurologic lesions; neurodegeneration of purkinje cells with loss of dendrites, perineural vacuolations of the neuronal cytoplasm (spongiosis and neuronal necrosis in the brain. The concentrations of Cr, Cu, Pb, As, Cd, Mn, Ni, sulphates, ammonia, chloride and phosphate in the leachate samples were above standard permissible limits. The interactions of the neurotoxic constituents of the leachates induced the observed brain damage in the rats via oxidative damage. This suggests health risk in wildlife and human populations.

  7. Taurine content in different brain structures during ageing: effect on hippocampal synaptic plasticity.

    Science.gov (United States)

    Suárez, Luz M; Muñoz, María-Dolores; Martín Del Río, Rafael; Solís, José M

    2016-05-01

    A reduction in taurine content accompanies the ageing process in many tissues. In fact, the decline of brain taurine levels has been associated with cognitive deficits whereas chronic administration of taurine seems to ameliorate age-related deficits such as memory acquisition and retention. In the present study, using rats of three age groups (young, adult and aged) we determined whether the content of taurine and other amino acids (glutamate, serine, glutamine, glycine, alanine and GABA) was altered during ageing in different brain areas (cerebellum, cortex and hippocampus) as well non-brain tissues (heart, kidney, liver and plasma). Moreover, using hippocampal slices we tested whether ageing affects synaptic function and plasticity. These parameters were also determined in aged rats fed with either taurine-devoid or taurine-supplemented diets. With age, we found heterogeneous changes in amino acid content depending on the amino acid type and the tissue. In the case of taurine, its content was reduced in the cerebellum of adult and aged rats, but it remained unchanged in the hippocampus, cortex, heart and liver. The synaptic response amplitude decreased in aged rats, although the late phase of long-term synaptic potentiation (late-LTP), a taurine-dependent process, was not altered. Our study highlights the stability of taurine content in the hippocampus during ageing regardless of whether taurine was present in the diet, which is consistent with the lack of changes detected in late-LTP. These results indicate that the beneficial effects of taurine supplementation might be independent of the replenishment of taurine stores. PMID:26803657

  8. Aluminium toxicity in the rat liver and brain

    International Nuclear Information System (INIS)

    To investigate the etiology of Alzheimer's disease, we examined the brain and liver tissue uptake of aluminium 5-75 days after aluminium injection into healthy rats. Ten days after the last injection, Al was detected in the brain and the brain cell nuclei by particle-induced X-ray emission (PIXE) analysis. Al was also demonstrated in the liver and the liver cell nuclei by PIXE analysis and electron energy loss spectrometry (EELS). The morphological changes of the rat brain examined 75 days after the injection were similar to those which have been reportedly observed in the brain of patients with Alzheimer's disease. These results support the theory that Alzheimer's disease is caused by irreversible accumulation of aluminium in the brain, as well as the nuclei of brain cells. (orig.)

  9. 26Al uptake and accumulation in the rat brain

    Science.gov (United States)

    Yumoto, S.; Nagai, H.; Imamura, M.; Matsuzaki, H.; Hayashi, K.; Masuda, A.; Kumazawa, H.; Ohashi, H.; Kobayashi, K.

    1997-03-01

    To investigate the cause of Alzheimer's disease (senile dementia), 26Al incorporation in the rat brain was studied by accelerator mass spectrometry (AMS). When 26Al was injected into healthy rats, a considerable amount of 26Al entered the brain (cerebrum) through the blood-brain barrier 5 days after a single injection, and the brain 26Al level remained almost constant from 5 to 270 days. On the other hand, the level of 26Al in the blood decreased remarkably 75 days after injection. Approximately 89% of the 26Al taken in by the brain cell nuclei bound to chromatin. This study supports the theory that Alzheimer's disease is caused by irreversible accumulation of aluminium (Al) in the brain, and brain cell nuclei.

  10. Autoradiographic localization of imipramine binding in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Rainbow, T.C.; Biegon, A.; McEwen, B.S. (Rockefeller Univ., New York (USA))

    1982-02-05

    The authors have used the recent LKB film method of receptor autoradiography to determine the distribution of imipramine binding sites in sections of rat brain. They find that the location of imipramine binding sites parallels the known distribution of 5HT terminals in rat brain. This provides additional evidence that (/sup 3/H)imipramine labels the presynaptic uptake size for 5HT, and offers the possibility of labeling presynaptic uptake sites in vitro for quantitative autoradiography.

  11. Lipoprotein lipase is produced, regulated, and functional in rat brain.

    OpenAIRE

    Eckel, R.H.; Robbins, R J

    1984-01-01

    Lipoprotein lipase (LP lipase, triacylglycero-protein acylhydrolase EC 3.1.1.34) activity was found in four dissimilar brain regions (hypothalamus, cortex, cerebellum, and midbrain) of adult male rats. Progressive accumulation of LP lipase activity in cultured fetal rat hypothalamic cells was also observed, indicating de novo synthesis of the lipase. The brain LP lipase activity was serum-dependent and was inhibited by 1 M NaCl and by protamine sulfate. Kinetic analysis revealed an apparent K...

  12. The pituitary - Aging and spaceflown rats

    Science.gov (United States)

    Hymer, W. C.; Grindeland, R. E.

    1991-01-01

    Decrements in growth hormone (GH) release we observed in two spaceflight experiments and four tail-suspended rat studies mimic age-associated changes in the mammalian pituitary GH system seen by Meites and others. The spaceflight data suggest that formation of high molecular weight bioactive disulfide-linked aggregates of the 20 and 22K monomeric GH forms may be reduced in microgravity, thereby, reducing target tissue activity. Correlative studies to confirm spaceflight as a model for pituitary GH system aging should include: (1) investigation of mechanisms of intracellular hormone packaging, (2) consequences to biological activity of the hormone molecule, and (3) study of intracellular microtubule dynamics.

  13. Effect of high fat diet on metabolic indices, cognition and neuronal physiology in aging F344 rats

    OpenAIRE

    Pancani, Tristano; Anderson, Katie L.; Lawrence D Brewer; Kadish, Inga; DeMoll, Chris; Landfield, Philip W.; Blalock, Eric M.; Porter, Nada M.; Thibault, Olivier

    2013-01-01

    The prevalence of obesity and type 2 diabetes increases with age. Despite this, few studies have examined these conditions simultaneously in aged animals, and fewer studies have measured the impact of these conditions on brain function. Using an established animal model of brain aging (F344 rats), we investigated whether high fat diet (HFD) exacerbates cognitive decline and the hippocampal calcium-dependent afterhyperpolarization (a marker of age-dependent calcium dysregulation). Young and mi...

  14. The effect of aging on synaptosomal Ca2+ transport in the brain.

    Science.gov (United States)

    Sun, A Y; Seaman, R N

    1977-03-01

    The effect of aging on Ca2+ -transport in synaptosomal preparations from rat brains was assessed by measuring the accumulation of radioactive 45Ca within these particles. Four groups of rats at 6, 12 24 and 30 months of age were used for this study. Synaptosomal particles were isolated from the cerebral cortex of each animal and the radioactive 45Ca inside the particles were measured after incubating the particles with media containing an energy source and 45Ca Cl2. Results indicated that the transport of 45Ca was lower in the younger rats than the older groups. A 20% increase was consistent with the old rats (30 mo) as compared with the young ones (6 mo). The increase in Ca2+ -transport across synaptic plasma membranes may be related to the transmitter release and behavioral activity after senescence. PMID:885150

  15. Successful brain aging: plasticity, environmental enrichment, and lifestyle

    OpenAIRE

    Mora, Francisco

    2013-01-01

    Aging is a physiological process that can develop without the appearance of concurrent diseases. However, very frequently, older people suffer from memory loss and an accelerated cognitive decline. Studies of the neurobiology of aging are beginning to decipher the mechanisms underlying not only the physiology of aging of the brain but also the mechanisms that make people more vulnerable to cognitive dysfunction and neurodegenerative diseases. Today we know that the aging brain retains a consi...

  16. Neuroimaging studies of the aging HIV-1-infected brain

    OpenAIRE

    Holt, John L.; Kraft-Terry, Stephanie D.; Chang, Linda

    2012-01-01

    Highly active antiretroviral therapy (HAART) has increased life expectancy among HIV-infected individuals, and by 2015, at least half of all HIV-infected individuals will be over 50 years of age. Neurodegenerative processes associated with aging may be facilitated by HIV-1 infection, resulting in premature brain aging. This review will highlight brain abnormalities in HIV patients in the setting of aging, focusing on recent neuroimaging studies of the structural, physiological, functional and...

  17. Impairments of astrocytes are involved in the D-galactose-induced brain aging

    International Nuclear Information System (INIS)

    Astrocyte dysfunction is implicated in course of various age-related neurodegenerative diseases. Chronic injection of D-galactose can cause a progressive deterioration in learning and memory capacity and serve as an animal model of aging. To investigate the involvement of astrocytes in this model, oxidative stress biomarkers, biochemical and pathological changes of astrocytes were examined in the hippocampus of the rats with six weeks of D-galactose injection. D-galactose-injected rats displayed impaired antioxidant systems, an increase in nitric oxide levels, and a decrease in reduced glutathione levels. Consistently, western blotting and immunostaining of glial fibrillary acidic protein showed extensive activation of astrocytes. Double-immunofluorescent staining further showed activated astrocytes highly expressed inducible nitric oxide synthase. Electron microscopy demonstrated the degeneration of astrocytes, especially in the aggregated area of synapse and brain microvessels. These findings indicate that impairments of astrocytes are involved in oxidative stress-induced brain aging by chronic injection of D-galactose

  18. The effects of aging on dopaminergic neurotransmission: a microPET study of [11C]-raclopride binding in the aged rodent brain.

    Science.gov (United States)

    Hoekzema, E; Herance, R; Rojas, S; Pareto, D; Abad, S; Jiménez, X; Figueiras, F P; Popota, F; Ruiz, A; Torrent, È; Fernández-Soriano, F J; Rocha, M; Rovira, M; Víctor, V M; Gispert, J D

    2010-12-29

    Rodent models are frequently used in aging research to investigate biochemical age effects and aid in the development of therapies for pathological and non-pathological age-related degenerative processes. In order to validate the use of animal models in aging research and pave the way for longitudinal intervention-based animal studies, the consistency of cerebral aging processes across species needs to be evaluated. The dopaminergic system seems particularly susceptible to the aging process, and one of the most consistent findings in human brain aging research is a decline in striatal D2-like receptor (D2R) availability, quantifiable by positron emission tomography (PET) imaging. In this study, we aimed to assess whether similar age effects can be discerned in rat brains, using in vivo molecular imaging with the radioactive compound [(11)C]-raclopride. We observed a robust decline in striatal [(11)C]-raclopride uptake in the aged rats in comparison to the young control group, comprising a 41% decrement in striatal binding potential. In accordance with human studies, these results indicate that substantial reductions in D2R availability can be measured in the aged striatal complex. Our findings suggest that rat and human brains exhibit similar biochemical alterations with age in the striatal dopaminergic system, providing support for the pertinence of rodent models in aging research.

  19. Parameters of glucose metabolism and the aging brain

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  20. The expression of Fetuin-A in brain tissues of WAG/Rij Rats, genetic rat model of absence epilepsy

    Directory of Open Access Journals (Sweden)

    Ramazan Yüksel

    2015-12-01

    Full Text Available Objective: In the present study, we aimed to determine the Fetuin-A levels in different regions of the brain in absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij rats in order to contribute the identification of new potential biomarkers of the diagnosis, prognosis and follow up the epilepsy treatment. Methods: 1, 3 and 6 months old male WAG/Rij rats (n=21 with absence epilepsy were used in this study. All of the rats were decapitated under anesthesia and their cortex and thalamus tissues were isolated. Fetuin-A levels of the groups were determined by Western Blot method by using standard techniques and differences between densities of the groups were compared. Results: According to data obtained, there was no Fetuin-A expression in brain cortex and thalamus tissues of WAG/Rij rats with absence epilepsy. Conclusion: In this study, it was shown that Fetuin-A is not expressed in brain cortex and thalamus tissues of WAG/Rij rats with absence epilepsy throughout the age-related development. By evaluating the findings obtained, extensive researches that contain molecular and histological methods must be planned, Fetuin-A findings that are obtained experimentally must be confirmed. J Clin Exp Invest 2015; 6 (4: 387-390

  1. Transport of 3-hydroxybutyrate by cultured rat brain astrocytes

    International Nuclear Information System (INIS)

    Studies by a number of investigators have shown that 3-hydroxybutyrate is a preferred energy substrate for brain during early development. Since recent studies by the authors group suggest that the utilization of oxidizable substrates by brain may be regulated in part by transport across the plasma membrane, the authors investigated the transport of [3H] D- and L-3-hydroxybutyrate and 3-hydroxy-[3-14C] butyrate by primary cultures of rat brain astrocytes. The data is consistent with the hypothesis that 3-hydroxybutyrate is taken up into cultured rat brain astrocytes by both diffusion and a carrier mediated transport system, and further support the concept that transport at the cellular level contributes to the regulation of substrate utilization by brain cells

  2. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    Science.gov (United States)

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population. PMID:26184082

  3. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    Science.gov (United States)

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population.

  4. Shaping the aging brain: Role of auditory input patterns in the emergence of auditory cortical impairments

    Directory of Open Access Journals (Sweden)

    Brishna Soraya Kamal

    2013-09-01

    Full Text Available Age-related impairments in the primary auditory cortex (A1 include poor tuning selectivity, neural desynchronization and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function.

  5. Comparison of catalase immunoreactivity in the hippocampus between young, adult and aged mice and rats.

    Science.gov (United States)

    Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Lee, Tae-Kyeong; Cho, Jeong Hwi; Kim, In Hye; Park, Joon Ha; Lee, Jae-Chul; Tae, Hyun-Jin; Lee, Choong-Hyun; Won, Moo-Ho; Lee, Yun Lyul; Choi, Soo Young; Hong, Seongkweon

    2016-07-01

    Catalase (CAT) is an important antioxidant enzyme and is crucial in modulating synaptic plasticity in the brain. In this study, CAT expression as well as neuronal distribution was compared in the hippocampus among young, adult and aged mice and rats. Male ICR mice and Sprague Dawley rats were used at postnatal month (PM) 1, PM 6 and PM 24 as the young, adult and aged groups, respectively (n=14/group). CAT expression was examined by immunohistochemistry and western blot analysis. In addition, neuronal distribution was examined by NeuN immunohistochemistry. In the present study, the mean number of NeuN‑immunoreactive neurons was marginally decreased in mouse and rat hippocampi during aging, although this change was not identified to be significantly different. However, CAT immunoreactivity was significantly increased in pyramidal and granule neurons in the adult mouse and rat hippocampi and was significantly decreased in the aged mouse and rat hippocampi compared with that in the young animals. CAT protein levels in the hippocampus were also lowest in the aged mouse and rat hippocampus. These results indicate that CAT expression is significantly decreased in the hippocampi of aged animals and decreased CAT expression may be closely associated with aging. PMID:27221506

  6. Cocaine disposition in discrete regions of rat brain.

    Science.gov (United States)

    Javaid, J I; Davis, J M

    1993-05-01

    It has been proposed that various effects of psychoactive drugs on the central nervous system may be related to the capacity of the drug to selectively concentrate in specific regions of the brain. In rat brain, cocaine effects on striatal and nucleus accumbens dopaminergic systems show quantitative differences. However, the disposition of cocaine in various brain regions has not been reported. In the present studies we examined the cocaine concentrations over time in serum and discrete brain regions of the rat after single intraperitoneal (i.p.) injection. At different time points (5, 10, 20, 30, 60, 120, and 240 min) after i.p. injection of cocaine hydrochloride (10 mg kg-1, free base) the rats were decapitated and cocaine in serum and various brain regions was quantitated by a specific gas liquid chromatographic method. There was large inter-individual variability in different rats at each time-point. The disposition pattern of cocaine in rats after i.p. administration was similar to that observed in humans after intranasal administration. Initial absorption rate was rapid and, on average, the peak levels of cocaine were achieved in 10 min. The cocaine levels remained relatively high over the next 50 min indicating continual absorption, and then declined with a rate such that the levels 4 h after cocaine administration were undetectable in most of the animals. The overall changes in cocaine levels in various brain regions paralleled the serum concentrations. The area under the cocaine concentration-time curve (AUC) revealed more than three-fold differences in cocaine accumulation in various brain regions. This unequal disposition of cocaine may be responsible in part for differential biochemical effects in different brain regions. PMID:8499585

  7. A longitudinal study of brain volume changes in normal aging

    International Nuclear Information System (INIS)

    Purpose: To evaluate the effect of normal aging on brain volumes and examine the effects of age and sex on the rates of changes in global and regional brain volumes. Methods: A total of 199 normal subjects (65 females and 134 males, mean age = 56.4 ± 9.9 years, age range = 38.1–82.9 years) were included in this study. Each subject was scanned twice, at an interval of about 2 years (range = 1.5–2.3 years). Two-time-point percentage brain volume change (PBVC) was estimated with SIENA 2.6. Results: The mean annualized PBVC was −0.23%/y. Analysis of covariance (ANCOVA) for annual brain volume changes revealed a main effect of age. There was no main effect of sex, nor was there a sex-by-age interaction. Voxel-wise analysis revealed a negative correlation between age and edge displacement values mainly in the periventricular region. Conclusions: The results of our study indicate that brain atrophy accelerates with increasing age and that there is no gender difference in the rate of brain atrophy

  8. Effect of Pomegranate Juice and Apple Juice on Free Radical Metabolism in Liver, Heart and Brain of Aged Rats%石榴汁和苹果汁干预对老龄大鼠肝、心、脑组织自由基代谢的影响

    Institute of Scientific and Technical Information of China (English)

    徐静; 刁焕荣; 拱玉华; 郭长江; 韦京豫; 杨继军

    2011-01-01

    Objective To study the effect of pomegranate juice and apple juice on free radical metabolism in the liver, heart and brain tissues of aged rats. Methods Thirty aged Wistar rats (22 months old) were randomly divided into three groups: pomegranate juice and apple juice as two experimental groups, while distilled water as normal control group. They were administrated fruit juices or distilled water respectively by gavage daily for 4 weeks. At the end of experiment, total antioxidant capacity (TAOC), content of MDA and free radical of the liver, heart and brain tissues were measured. Results The aged rats in pomegranate group showed significantly higher TAOC and lower content of free radicals in liver and brain respectively, while the concentrations of MDA in the liver, brain and heart tissues declined remarkably as compared to control group. The concentration of MDA and content of free radical in the liver tissue of aged rats in apple juice group decreased significantly. The pomegranate juice and apple juice had no evident effect on TAOC and concentration of free radical in the heart tissue of aged rats. Conclusion The pomegranate juice which showed stronger antioxidant capacity in vitro possessed higher capability to improve the metabolism offree radical in the liver, heart and brain tissues of aged rats.%目的 研究抗氧化活性较强的石榴汁和较弱的苹果汁对老龄大鼠肝、心、脑组织自由基代谢的影响.方法 自然衰老Wistar大鼠(22月龄)30只,随机分为三组,分别灌胃石榴汁3.2 ml,苹果汁2.4 ml和蒸馏水3.2 ml(对照组),实验周期4周,实验结束后取大鼠肝、心、脑组织制作匀浆液测定总抗氧化力、丙二醛(MDA)及自由基含量.结果 石榴汁干预组老龄大鼠肝脏、脑组织抗氧化能力显著升高、自由基水平明显下降,肝、心、脑MDA含量均显著降低,与对照组比较差异有统计学意义;苹果汁干预后老龄大鼠肝组织MDA含量及自由基水平明显

  9. Accelerated brain aging in schizophrenia : A longitudinal pattern recognition study

    NARCIS (Netherlands)

    Schnack, Hugo G.; Van Haren, Neeltje E M; Nieuwenhuis, Mireille; Pol, Hilleke E Hulshoff; Cahn, Wiepke; Kahn, René S.

    2016-01-01

    OBJECTIVE: Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used

  10. Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Lifang Lei; Xiaohong Zi; Qiuyun Tu

    2008-01-01

    BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 (MMP-9) is closely related to cerebral ischemia/reperfusion injuryOBJECTIVE: This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability.DESIGN, TIME AND SETTING: This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006.MATERIALS: Ninety healthy male SD rats, aged 3-4 months, weighing 200-280g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody (Boster, Wuhan, China) and Evans blue (Sigma, USA) were also used.METHODS: All rats were randomly divided into 9 groups with 10 rats in each group: normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3,6,12 hours, 1,2,4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled.MAIN OUTCOME MEASURES: BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method.RESULTS: All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter

  11. Modeling the brain morphology distribution in the general aging population

    Science.gov (United States)

    Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

    2016-03-01

    Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

  12. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats

    Directory of Open Access Journals (Sweden)

    Mohamed Naguib Zakaria

    2015-01-01

    Full Text Available Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE, AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS complications in STZ-induced (50 mg/kg, IP diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze, neuronal degeneration (Fluoro-Jade staining, AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde. These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications.

  13. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats.

    Science.gov (United States)

    Zakaria, Mohamed Naguib; El-Bassossy, Hany M; Barakat, Waleed

    2015-01-01

    Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs) is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE), AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE) and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS) complications in STZ-induced (50 mg/kg, IP) diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze), neuronal degeneration (Fluoro-Jade staining), AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde). These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications. PMID:26491434

  14. Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state

    OpenAIRE

    Briones, Teresita L; Darwish, Hala

    2014-01-01

    In the present study we examined whether vitamin D supplementation can reduce age-related tau hyperphosphorylation and cognitive impairment by enhancing brain energy homeostasis and protein phosphatase-2A (PP2A) activity, and modulating the redox state. Male F344 rats age 20 months (aged) and 6 months (young) were randomly assigned to either vitamin D supplementation or no supplementation (control). Rats were housed in pairs and the supplementation group (n=10 young and n=10 aged) received su...

  15. Statistical Approaches for the Study of Cognitive and Brain Aging

    Science.gov (United States)

    Chen, Huaihou; Zhao, Bingxin; Cao, Guanqun; Proges, Eric C.; O'Shea, Andrew; Woods, Adam J.; Cohen, Ronald A.

    2016-01-01

    Neuroimaging studies of cognitive and brain aging often yield massive datasets that create many analytic and statistical challenges. In this paper, we discuss and address several limitations in the existing work. (1) Linear models are often used to model the age effects on neuroimaging markers, which may be inadequate in capturing the potential nonlinear age effects. (2) Marginal correlations are often used in brain network analysis, which are not efficient in characterizing a complex brain network. (3) Due to the challenge of high-dimensionality, only a small subset of the regional neuroimaging markers is considered in a prediction model, which could miss important regional markers. To overcome those obstacles, we introduce several advanced statistical methods for analyzing data from cognitive and brain aging studies. Specifically, we introduce semiparametric models for modeling age effects, graphical models for brain network analysis, and penalized regression methods for selecting the most important markers in predicting cognitive outcomes. We illustrate these methods using the healthy aging data from the Active Brain Study. PMID:27486400

  16. Brain Damage in School Age Children.

    Science.gov (United States)

    Haywood, H. Carl, Ed.

    The product of a professional workshop, 10 papers discuss brain damage. An introduction to clinical neuropsychology is presented by H. Carl Haywood. A section on neurological foundations includes papers on the organization of the central nervous system by Jack T. Tapp and Lance L. Simpson, on epilepsy by Angela T. Folsom, and on organic language…

  17. Ageing and diabetes: implications for brain function

    NARCIS (Netherlands)

    Gispen, W.H.; Biessels, G.J.; Heide, L.P. van der; Kamal, A.; Bleys, R.L.A.W.

    2002-01-01

    Diabetes mellitus is associated with moderate cognitive deficits and neurophysiological and structural changes in the brain, a condition that may be referred to as diabetic encephalopathy. Diabetes increases the risk of dementia, particularly in the elderly. The emerging view is that the diabetic br

  18. Distribution of nimodipine in brain following intranasal administration in rats

    Institute of Scientific and Technical Information of China (English)

    Qi-zhi ZHANG; Xin-guo JIANG; Chun-hua WU

    2004-01-01

    AIM: To determine whether nasally applied nimodipine (NM) could improve its systemic bioavailability and be transported directly from the nasal cavity to the brain. METHODS: NM was administered nasally, intravenously (iv), and orally to male Sprague-Dawley rats. At different times post dose, blood, cerebrospinal fluid (CSF), and brain tissue samples were collected, and the concentrations of NM in the samples were analyzed by HPLC. RESULTS:Oral systemic bioavailability of NM in rats was 1.17 %, nasal dosing improved bioavailibility to 67.4 %. Following intranasal administration, NM concentrations in olfactory bulb (OB) within 30 min post dose were found significant higher than in the other brain tissues. However, similar NM levels in different brain regions were observed after iv injection. AUC in CSF and OB from the nasal route was 1.26 and 1.39 fold compared with the iv route, respectively.The brain-to-plasma AUC ratios were significantly higher after nasal administration than after iv administration (P<0.01). CONCLUSION: Nasally administered NM could markedly improve the bioavailability and a fraction of the NM dose could be transported into brain via the olfactory pathway in rats.

  19. Aging differentially affects the loss of neuronal dendritic spine, neuroinflammation and memory impairment at rats after surgery.

    Directory of Open Access Journals (Sweden)

    Yuan Le

    Full Text Available It is known that age is an important factor for postoperative cognitive dysfunction (POCD and the patients with POCD suffer from the impairment of multiple brain regions and multiple brain functions. However currently animal studies of POCD mainly focus on hippocampus region, therefore in this study we performed partial hepatectomy in young adult and aged rats to test the questions (1 whether POCD in animals involves other brain areas besides hippocampus; (2 how age influences POCD of young adult and aged animals. We found that (1 in young adult rats, the memory was not significantly affected (P>0.05 1d, 3d and 7d after partial hepatectomy, but was significantly impaired (p0.05, respectively 1d and 3d post-surgery, but the spine densities at CA1 and DG of aged rats were significant reduced 1d and 3d post-surgery (p0.05; (3 In young adult rats, surgery didn't affect the activation of microglia and levels of TNF-α and IL-1β at hippocampus (P>0.05, but significantly activated microglia and increased levels of TNF-α and IL-1β at hippocampus of aged rats (P<0.05. Our data suggest that (1 partial hepatectomy-induced POCD mainly involves hippocampus impairments, and (2 differential loss of neuronal dendritic spines and neuroinflammation at hippocampus are most likely the mechanism for the formation of POCD in aged rats.

  20. Effect of ketamine on aquaporin-4 expression and neuronal apoptosis in brain tissues following brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Zangong Zhou; Xiangyu Ji; Li Song; Jianfang Song; Shiduan Wang; Yanwei Yin

    2006-01-01

    BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats.OBJECTIVE: To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury.DESIGN: Randomized grouping design, controlled animal trial.SETTING: Department of Anesthesiology, the Medical School Hospital of Qingdao University.MATERIALS: Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents:homemade beat machine, ketamine hydrochloride (Hengrui Pharmaceutical Factory, Jiangsu), rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit (Boster Co.,Ltd.,Wuhan).METHODS: This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine (120 mg/kg) one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal

  1. Brain catecholamines in spontaneously hypertensive and DOCA-salt hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Fujino,Kazuyuki

    1984-08-01

    Full Text Available The concentrations and alpha-methyl-p-tyrosine (alpha-MPT induced disappearance of catecholamines, adrenaline, noradrenaline and dopamine, were measured in selected areas of the brainstem and hypothalamus of spontaneously hypertensive rats (SHR and deoxycorticosterone acetate (DOCA-salt hypertensive rats. The catecholamine levels were measured by a sensitive radioenzymatic assay method combined with microdissection of the rat brain. The adrenaline concentration was higher in the area A1 of young SHR, but not in adult SHR, than in age-matched control rats. Noradrenaline concentrations and the alpha-MPT induced noradrenaline disappearance were less in the rostral part of the nucleus tractus solitarii (NTS and the nucleus hypothalamic anterior of young SHR, and in the rostral part of the NTS of adult SHR. On the other hand in DOCA-salt hypertensive rats, the concentrations of adrenaline and noradrenaline were the same as in control rats in the examined areas. The alpha-MPT induced noradrenaline disappearance was less in the rostral part of the NTS of DOCA-salt hypertensive rats. Dopamine concentrations and the alpha-MPT induced dopamine disappearance were the same in the examined areas of SHR and DOCA-salt hypertensive rats. The results suggest that SHR have a change in adrenergic neural activity in the brainstem and a decrease in noradrenergic neural activity in the brainstem and hypothalamus while DOCA-salt hypertensive rats have a decrease in noradrenergic neural activity in the brainstem. Such changes in brain catecholaminergic neurons may have played an important role in the development of hypertension in these rats.

  2. The rate of training response to aerobic exercise affects brain function of rats.

    Science.gov (United States)

    Marton, Orsolya; Koltai, Erika; Takeda, Masaki; Mimura, Tatsuya; Pajk, Melitta; Abraham, Dora; Koch, Lauren Gerard; Britton, Steven L; Higuchi, Mitsuru; Boldogh, Istvan; Radak, Zsolt

    2016-10-01

    There is an increasing volume of data connecting capacity to respond to exercise training with quality of life and aging. In this study, we used a rat model in which animals were selectively bred for low and high gain in running distance to test t whether genetic segregation for trainability is associated with brain function and signaling processes in the hippocampus. Rats selected for low response (LRT) and high response training (HRT) were randomly divided into control or exercise group that trained five times a week for 30 min per day for three months at 70% VO2max. All four groups had similar running distance before training. With training, HRT rats showed significantly greater increases in VO2max and running distance than LRT rats (p brain-derived neurotrophic factor (BDNF), ratio of phospho and total cAMP-response element binding protein (CREB), and apoptotic index, also showed significant differences between LRT and HRT groups. These findings suggest that aerobic training responses are not localized to skeletal muscle, but differently involve signaling processes in the brain of LRT and HRT rats. PMID:27262284

  3. Muscarinic receptor plasticity in the brain of senescent rats: down-regulation after repeated administration of diisopropyl fluorophosphate

    Energy Technology Data Exchange (ETDEWEB)

    Pintor, A.; Fortuna, S.; Volpe, M.T.; Michalek, H.

    1988-01-01

    Potential age-related differences in the response of Fischer 344 rats to subchronic treatment with diisopropylfluorophosphate (DFP) were evaluated in terms of brain cholinesterase (ChE) inhibition and muscarinic receptor sites. Male 3- and 24-month old rats were sc injected with sublethal doses of DFP for 2 weeks and killed 48 hrs after the last treatment. In the cerebral cortex, hippocampus and striatum of control rats a significant age-related reduction of ChE and of maximum number of /sup 3/H-QNB binding sites (Bmax) was observed. The administration of DFP to senescent rats resulted in more pronounced and longer lasting syndrome of cholinergic stimulation, with marked body weight loss and 60% mortality. The percentage inhibition of brain ChE induced by DFP did not differ between young and senescent rats. As expected, in young rats DFP caused a significant decrease of Bmax, which in the cerebral cortex reached about 40%. In the surviving senescent rats, the percentage decrease of Bmax due to DFP with respect to age-matched controls was very similar to that of young animals, especially in the cerebral cortex. Thus there is great variability in the response of aged rats to DFP treatment, from total failure of adaptive mechanisms resulting in death to considerable muscarinic receptor plasticity.

  4. Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

    Directory of Open Access Journals (Sweden)

    Marta Karolina Zamroziewicz

    2016-06-01

    Full Text Available Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition’s impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition – from entire diets to specific nutrients – affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns, along with (ii modern indices of brain health derived from high-resolution magnetic resonance imaging. By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

  5. Emotion and Aging: Evidence from Brain and Behavior

    Directory of Open Access Journals (Sweden)

    Natalie eEbner

    2014-09-01

    Full Text Available Emotions play a central role in every human life from the moment we are born until we die. They prepare the body for action, highlight what should be noticed and remembered, and guide decisions and actions. As emotions are central to daily functioning, it is important to understand how aging affects perception, memory, experience, as well as regulation of emotions. The Frontiers research topic Emotion and Aging: Evidence from Brain and Behavior takes a step into uncovering emotional aging considering both brain and behavioral processes. The contributions featured in this issue adopt innovative theoretical perspectives and use novel methodological approaches to target a variety of topics that can be categorized into three overarching questions: How do cognition and emotion interact in aging in brain and behavior? What are behavioral and brain-related moderators of emotional aging? Does emotion-regulatory success as reflected in brain and behavior change with age? In this perspective paper we discuss theoretical innovation, methodological approach, and scientific advancement of the thirteen papers in the context of the broader literature on emotional aging. We conclude by reflecting on topics untouched and future directions to take.

  6. Do brain image databanks support understanding of normal ageing brain structure? A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Dickie, David Alexander; Job, Dominic E.; Wardlaw, Joanna M. [University of Edinburgh, Division of Clinical Neurosciences, Western General Hospital, Brain Research Imaging Centre (BRIC), Edinburgh (United Kingdom); Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE), Edinburgh (United Kingdom); Poole, Ian [Toshiba Medical Visualisation Systems Europe, Ltd., Edinburgh (United Kingdom); Ahearn, Trevor S.; Staff, Roger T.; Murray, Alison D. [University of Aberdeen, Aberdeen Biomedical Imaging Centre, Aberdeen (United Kingdom); Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE), Edinburgh (United Kingdom)

    2012-07-15

    To document accessible magnetic resonance (MR) brain images, metadata and statistical results from normal older subjects that may be used to improve diagnoses of dementia. We systematically reviewed published brain image databanks (print literature and Internet) concerned with normal ageing brain structure. From nine eligible databanks, there appeared to be 944 normal subjects aged {>=}60 years. However, many subjects were in more than one databank and not all were fully representative of normal ageing clinical characteristics. Therefore, there were approximately 343 subjects aged {>=}60 years with metadata representative of normal ageing, but only 98 subjects were openly accessible. No databank had the range of MR image sequences, e.g. T2*, fluid-attenuated inversion recovery (FLAIR), required to effectively characterise the features of brain ageing. No databank supported random subject retrieval; therefore, manual selection bias and errors may occur in studies that use these subjects as controls. Finally, no databank stored results from statistical analyses of its brain image and metadata that may be validated with analyses of further data. Brain image databanks require open access, more subjects, metadata, MR image sequences, searchability and statistical results to improve understanding of normal ageing brain structure and diagnoses of dementia. (orig.)

  7. Influence of age on brain edema formation, secondary brain damage and inflammatory response after brain trauma in mice.

    Directory of Open Access Journals (Sweden)

    Ralph Timaru-Kast

    Full Text Available After traumatic brain injury (TBI elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months and old (21 months male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2% compared to young (0%. This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1β expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral

  8. Neuroprotective effect of Shenqi Fuzheng injection pretreatment in aged rats with cerebral ischemia/reperfusion injury

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    Ying-min Cai

    2016-01-01

    Full Text Available Shenqi Fuzheng injection is extracted from the Chinese herbs Radix Astragali and Radix Codonopsis. The aim of the present study was to investigate the neuroprotective effects of Shenqi Fuzheng injection in cerebral ischemia and reperfusion. Aged rats (20-22 months were divided into three groups: sham, model, and treatment. Shenqi Fuzheng injection or saline (40 mL/kg was injected into the tail vein daily for 1 week, after which a cerebral ischemia/reperfusion injury model was established. Compared with model rats that received saline, rats in the treatment group had smaller infarct volumes, lower brain water and malondialdehyde content, lower brain Ca 2+ levels, lower activities of serum lactate dehydrogenase and creatine kinase, and higher superoxide dismutase activity. In addition, the treatment group showed less damage to the brain tissue ultrastructure and better neurological function. Our findings indicate that Shenqi Fuzheng injection exerts neuroprotective effects in aged rats with cerebral ischemia/reperfusion injury, and that the underlying mechanism relies on oxygen free radical scavenging and inhibition of brain Ca 2+ accumulation.

  9. Titanium dioxide nanoparticles decreases activity of rat brain when administered prenatally

    Directory of Open Access Journals (Sweden)

    Nikita Saraswat

    2016-06-01

    Conclusions: We studied the neurobehaviour of progenies, when the drug was administered to rat brain prenatally. The results showed that the titanium dioxide nanoparticles particles have decreased the brain activity of the rat brain by showing decreased brain activity in progenies also. [Int J Basic Clin Pharmacol 2016; 5(3.000: 733-738

  10. Autoradiographic localization of relaxin binding sites in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Osheroff, P.L.; Phillips, H.S. (Genentech, Inc., South San Francisco, CA (USA))

    1991-08-01

    Relaxin is a member of the insulin family of polypeptide hormones and exerts its best understood actions in the mammalian reproductive system. Using a biologically active 32P-labeled human relaxin, the authors have previously shown by in vitro autoradiography specific relaxin binding sites in rat uterus, cervix, and brain tissues. Using the same approach, they describe here a detailed localization of human relaxin binding sites in the rat brain. Displaceable relaxin binding sites are distributed in discrete regions of the olfactory system, neocortex, hypothalamus, hippocampus, thalamus, amygdala, midbrain, and medulla of the male and female rat brain. Characterization of the relaxin binding sites in the subfornical organ and neocortex reveals a single class of high-affinity sites (Kd = 1.4 nM) in both regions. The binding of relaxin to two of the circumventricular organs (subfornical organ and organum vasculosum of the lamina terminalis) and the neurosecretory magnocellular hypothalamic nuclei (i.e., paraventricular and supraoptic nuclei) provides the anatomical and biochemical basis for emerging physiological evidence suggesting a central role for relaxin in the control of blood pressure and hormone release. They conclude that specific, high-affinity relaxin binding sites are present in discrete regions of the rat brain and that the distribution of some of these sites may be consistent with a role for relaxin in control of vascular volume and blood pressure.

  11. The effect of chemotherapy on rat brain PET: preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Su; Kim, Il Han; Yu, A Ram; Park, Ji Ae; Woo, Sang Keun; Kim, Jong Guk; Cheon, Gi Jeong; Kim, Byeong Il; Choi, Chang Woon; Lim, Sang Moo; Kim, Hee Joung; Kim, Kyeong Min [Korea Institute Radiological and Medical Science, Seoul (Korea, Republic of)

    2010-10-15

    Chemotherapy was widely used for the therapy of cancer patients. When chemotherapy was performed, transient cognitive memory problem was occurred. This cognitive problem in brain was called as chemobrain. In this study, we have developed rat model for chemobrain. Cerebral glucose metabolism after chemotherapy was assessed using animal PET and voxel based statistical analysis method

  12. Brain tumors induced in rats by human adenovirus type 12

    Directory of Open Access Journals (Sweden)

    Murao,Tsuyoshi

    1974-02-01

    Full Text Available Oncogenesis of human adenovirus type 12 in the brain of rats was examined. Newborn rats of Sprague-Dawley and Donryu strains were injected intracranially with human adenovirus type 12. The incidence of intracranial tumors was 91% (30/33 in SpragueDawley and 56% (14/25 in Donryu rats. Except for one tumor nodule located in the parietal cortex of a Sprague.Dawley rat, all tumors developed in the paraventricular areas or in the meninges. Tumors were quite similar histologically to those induced in hamsters and mice resembling the undifferentiated human brain tumors such as medulloblastoma, ependymoblastoma and embryonic gliomas. From the histological features and primary sites of tumor development, it is suggested that the tumors in the brain of rats induced by adenovirus type 12 originate from the embryonic cells in the paraventricular area and also from the undifferentiated supporting cells of the peripheral nerves in the leptomeninges.

  13. Effects of magnesium sulfate on traumatic brain edema in rats

    Institute of Scientific and Technical Information of China (English)

    冯东福; 朱志安; 卢亦成

    2004-01-01

    Objective: To investigate the effects of magnesium sulfate on traumatic brain edema and explore its possible mechanism.Methods: Forty-eight Sprague-Dawley ( SD ) rats were randomly divided into three groups: Control, Trauma and Treatment groups. In Treatment group, magnesium sulfate was intraperitoneally administered immediately after the induction of brain trauma. At 24 h after trauma, total tissue water content and Na + , K + , Ca2 + , Mg2+ contents were measured. Permeability of blood-brain barrier (BBB)was assessed quantitatively by Evans Blue (EB) dye technique. The pathological changes were also studied.Results: Water, Na + , Ca2 + and EB contents in Treatment group were significantly lower than those in Trauma group ( P < 0. 05 ). Results of light microscopy and electron microscopy confirmed that magnesium sulfate can attenuate traumatic brain injury and relieve BBB injury.Conclusions: Treatment with MgSO4 in the early stage can attenuate traumatic brain edema and prevent BBB injury.

  14. Outer brain barriers in rat and human development

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

    2015-01-01

    diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post...... of the arachnoid blood-CSF barrier. Collagen 1 delineated the subarachnoid space and stained pial surface layer. BLBP defined radial glial end feet layer and SSEA-4 and YKL-40 were present in both leptomeningeal cells and end feet layer, which transformed into glial limitans. IL-13Rα2 and EAAT1 were present...... in the end feet layer illustrating transporter/receptor presence in the outer CSF-brain barrier. MAP2 immunostaining in adult brain outlined the lower border of glia limitans; remnants of end feet were YKL-40 positive in some areas. We propose that outer brain barriers are composed of at least 3 interfaces...

  15. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug.

    Science.gov (United States)

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D Chichung; Abbracchio, Maria P; Aigner, Ludwig

    2015-10-27

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias.

  16. Inducible gene manipulations in brain serotonergic neurons of transgenic rats.

    Directory of Open Access Journals (Sweden)

    Tillmann Weber

    Full Text Available The serotonergic (5-HT system has been implicated in various physiological processes and neuropsychiatric disorders, but in many aspects its role in normal and pathologic brain function is still unclear. One reason for this might be the lack of appropriate animal models which can address the complexity of physiological and pathophysiological 5-HT functioning. In this respect, rats offer many advantages over mice as they have been the animal of choice for sophisticated neurophysiological and behavioral studies. However, only recently technologies for the targeted and tissue specific modification of rat genes - a prerequisite for a detailed study of the 5-HT system - have been successfully developed. Here, we describe a rat transgenic system for inducible gene manipulations in 5-HT neurons. We generated a Cre driver line consisting of a tamoxifen-inducible CreERT2 recombinase under the control of mouse Tph2 regulatory sequences. Tissue-specific serotonergic Cre recombinase expression was detected in four transgenic TPH2-CreERT2 rat founder lines. For functional analysis of Cre-mediated recombination, we used a rat Cre reporter line (CAG-loxP.EGFP, in which EGFP is expressed after Cre-mediated removal of a loxP-flanked lacZ STOP cassette. We show an in-depth characterisation of this rat Cre reporter line and demonstrate its applicability for monitoring Cre-mediated recombination in all major neuronal subpopulations of the rat brain. Upon tamoxifen induction, double transgenic TPH2-CreERT2/CAG-loxP.EGFP rats show selective and efficient EGFP expression in 5-HT neurons. Without tamoxifen administration, EGFP is only expressed in few 5-HT neurons which confirms minimal background recombination. This 5-HT neuron specific CreERT2 line allows Cre-mediated, inducible gene deletion or gene overexpression in transgenic rats which provides new opportunities to decipher the complex functions of the mammalian serotonergic system.

  17. Alteration of CNS dopamine transporter and D2 receptor in aged and scopolamine induced amnestic rats

    International Nuclear Information System (INIS)

    Objective: To evaluate the effect of aging and scopolamine (Sco) induced amnesia on central dopamine transporter (DAT), D2 receptor in rats. Methods: The 3 month old amnestic rat models were made by peritoneal injection of the muscarinic receptor antagonist Sco (5 mg/kg) for 10 d. Passive avoidance task was carried out to evaluate the recent learning and memory of rats. The biodistribution of 125I-2-β-carbomethoxy-3-β(4-iodophenyl)-tropan (125I-β-CIT) and 125I-s-3-iodo-N-(1-ethyl-2-pyrolidinyl) methyl-2-hydroxy-6-methoxybenzamide (IBZM) in the brain was used to evaluate the DAT and D2 receptor. Results: During 10 d passive avoidance task testing, no difference was found for the first day among 3 month control, 26 month old and Sco group rats, on the 10th day the entry number of aged and Sco group rats was (1.33 +- 0.82)/10 min, (3.00 +- 0.63)/10 min, respectively, higher than that of the control rats (t was 5.682 and 6.372, respectively, P125I-β-CIT binding were found in the striatum (ST), hippocampus (HIP) and frontal cortex (FC) of the aged and Sco group rats (t was 4.151, 5.416, 4.871, 6.922, 7.331 and 3.990, respectively, P125I-IBZM binding in ST was found in both Sco and old rats (t was 6.021 and 3.227, respectively, P 2 receptor, was found in ST, HIP and cortex of the aged and Sco group suggesting a gradual degeneration of dopaminergic neurons in aged rats. The decreased levels of 125I-β-CIT and 125I-IBZM binding in cortex area might be responsible for the amnesia in he Sco group through the dopaminergic pathway of midbrain-frontal cortex

  18. Phospholipase C I and II brain isozymes: immunohistochemical localization in neuronal systems in rat brain.

    OpenAIRE

    Gerfen, C R; Choi, W C; Suh, P G; Rhee, S G

    1988-01-01

    Two distinct inositol phospholipid-specific phospholipase C (PLC; phosphatidylcholine phosphatidohydrolase, EC 3.1.4.3) isozymes, PLC-I and PLC-II, have been purified and characterized from bovine brain. Monoclonal antibodies that distinguish between these isozymes are used in the present study to map isozyme distribution in the rat brain with immunohistochemical techniques. Both isozymes are localized in neurons, and, whereas PLC-II is rather ubiquitous--being expressed in most neurons, PLC-...

  19. Tualang Honey Attenuates Noise Stress-Induced Memory Deficits in Aged Rats.

    Science.gov (United States)

    Azman, Khairunnuur Fairuz; Zakaria, Rahimah; Abdul Aziz, Che Badariah; Othman, Zahiruddin

    2016-01-01

    Ageing and stress exposure may lead to memory impairment while oxidative stress is thought to be one of the underlying mechanisms involved. This study aimed to investigate the potential protective effects of Tualang honey supplementation on memory performance in aged rats exposed to noise stress. Tualang honey supplementation was given orally, 200 mg/kg body weight for 28 days. Rats in the stress group were subjected to loud noise, 100 dB(A), 4 hours daily for 14 days. All rats were subjected to novel object recognition test for evaluation of memory performance. It was observed that the rats subjected to noise stress exhibited significantly lower memory performance and higher oxidative stress as evident by elevated malondialdehyde and protein carbonyl levels and reduction of antioxidant enzymes activities compared to the nonstressed rats. Tualang honey supplementation was able to improve memory performance, decrease oxidative stress levels, increase brain-derived neurotrophic factor (BDNF) concentration, decrease acetylcholinesterase activity, and enhance neuronal proliferation in the medial prefrontal cortex (mPFC) and hippocampus. In conclusion, Tualang honey protects against memory decline due to stress exposure and/or ageing via enhancement of mPFC and hippocampal morphology possibly secondary to reduction in brain oxidative stress and/or upregulation of BDNF concentration and cholinergic system. PMID:27119005

  20. Tualang Honey Attenuates Noise Stress-Induced Memory Deficits in Aged Rats

    Directory of Open Access Journals (Sweden)

    Khairunnuur Fairuz Azman

    2016-01-01

    Full Text Available Ageing and stress exposure may lead to memory impairment while oxidative stress is thought to be one of the underlying mechanisms involved. This study aimed to investigate the potential protective effects of Tualang honey supplementation on memory performance in aged rats exposed to noise stress. Tualang honey supplementation was given orally, 200 mg/kg body weight for 28 days. Rats in the stress group were subjected to loud noise, 100 dB(A, 4 hours daily for 14 days. All rats were subjected to novel object recognition test for evaluation of memory performance. It was observed that the rats subjected to noise stress exhibited significantly lower memory performance and higher oxidative stress as evident by elevated malondialdehyde and protein carbonyl levels and reduction of antioxidant enzymes activities compared to the nonstressed rats. Tualang honey supplementation was able to improve memory performance, decrease oxidative stress levels, increase brain-derived neurotrophic factor (BDNF concentration, decrease acetylcholinesterase activity, and enhance neuronal proliferation in the medial prefrontal cortex (mPFC and hippocampus. In conclusion, Tualang honey protects against memory decline due to stress exposure and/or ageing via enhancement of mPFC and hippocampal morphology possibly secondary to reduction in brain oxidative stress and/or upregulation of BDNF concentration and cholinergic system.

  1. Effect of ketamine on aquaporin-4 expression and neuronal apoptosis in brain tissues following brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Zangong Zhou; Xiangyu Ji; Li Song; Jianfang Song; Shiduan Wang; Yanwei Yin

    2006-01-01

    BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats.OBJECTIVE: To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury.DESIGN: Randomized grouping design, controlled animal trial.SETTING: Department of Anesthesiology, the Medical School Hospital of Qingdao University.MATERIALS: Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents:homemade beat machine, ketamine hydrochloride (Hengrui Pharmaceutical Factory, Jiangsu), rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit (Boster Co.,Ltd.,Wuhan).METHODS: This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine (120 mg/kg) one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal

  2. Chronic Methamphetamine Effects on Brain Structure and Function in Rats

    Science.gov (United States)

    Thanos, Panayotis K.; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J.; Masad, Ihssan; Muniz, Jose A.; Grant, Samuel C.; Gold, Mark S.; Cadet, Jean Lud; Volkow, Nora D.

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  3. Chronic Methamphetamine Effects on Brain Structure and Function in Rats.

    Directory of Open Access Journals (Sweden)

    Panayotis K Thanos

    Full Text Available Methamphetamine (MA addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET studies have shown decreased brain glucose metabolism (BGluM in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls, or low dose (LD MA (4 mg/kg, or high dose (HD MA (8 mg/kg. Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG, and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  4. Berry Fruit Supplementation in the Aging Brain

    Science.gov (United States)

    The onset of age-related neurodegenerative diseases such as Alzheimer’s or Parkinson’s Disease, superimposed on a declining nervous system, could exacerbate the motor and cognitive behavioral deficits that normally occur in senescence. In cases of severe deficits in memory or motor function, hospit...

  5. Aged rats are hypo-responsive to acute restraint: implications for psychosocial stress in aging

    OpenAIRE

    Eric Blalock

    2014-01-01

    Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/ stress hormone/ allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation), and aged humans ar...

  6. Abdominal surgery activates nesfatin-1 immunoreactive brain nuclei in rats.

    Science.gov (United States)

    Stengel, Andreas; Goebel, Miriam; Wang, Lixin; Taché, Yvette

    2010-02-01

    Abdominal surgery-induced postoperative gastric ileus is well established to induce Fos expression in specific brain nuclei in rats within 2-h after surgery. However, the phenotype of activated neurons has not been thoroughly characterized. Nesfatin-1 was recently discovered in the rat hypothalamus as a new anorexigenic peptide that also inhibits gastric emptying and is widely distributed in rat brain autonomic nuclei suggesting an involvement in stress responses. Therefore, we investigated whether abdominal surgery activates nesfatin-1-immunoreactive (ir) neurons in the rat brain. Two hours after abdominal surgery with cecal palpation under short isoflurane anesthesia or anesthesia alone, rats were transcardially perfused and brains processed for double immunohistochemical labeling of Fos and nesfatin-1. Abdominal surgery, compared to anesthesia alone, induced Fos expression in neurons of the supraoptic nucleus (SON), paraventricular nucleus (PVN), locus coeruleus (LC), Edinger-Westphal nucleus (EW), rostral raphe pallidus (rRPa), nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM). Double Fos/nesfatin-1 labeling showed that of the activated cells, 99% were nesfatin-1-immunoreactive in the SON, 91% in the LC, 82% in the rRPa, 74% in the EW and VLM, 71% in the anterior parvicellular PVN, 47% in the lateral magnocellular PVN, 41% in the medial magnocellular PVN, 14% in the NTS and 9% in the medial parvicellular PVN. These data established nesfatin-1 immunoreactive neurons in specific nuclei of the hypothalamus and brainstem as part of the neuronal response to abdominal surgery and suggest a possible implication of nesfatin-1 in the alterations of food intake and gastric transit associated with such a stressor. PMID:19944727

  7. In vivo calcium imaging of the aging and diseased brain

    Energy Technology Data Exchange (ETDEWEB)

    Eichhoff, Gerhard; Busche, Marc A.; Garaschuk, Olga [Technical University of Munich, Institute of Neuroscience, Munich (Germany)

    2008-03-15

    Over the last decade, in vivo calcium imaging became a powerful tool for studying brain function. With the use of two-photon microscopy and modern labelling techniques, it allows functional studies of individual living cells, their processes and their interactions within neuronal networks. In vivo calcium imaging is even more important for studying the aged brain, which is hard to investigate in situ due to the fragility of neuronal tissue. In this article, we give a brief overview of the techniques applicable to image aged rodent brain at cellular resolution. We use multicolor imaging to visualize specific cell types (neurons, astrocytes, microglia) as well as the autofluorescence of the ''aging pigment'' lipofuscin. Further, we illustrate an approach for simultaneous imaging of cortical cells and senile plaques in mouse models of Alzheimer's disease. (orig.)

  8. Expression of neuropeptide Y in rat brain ischemia

    Directory of Open Access Journals (Sweden)

    Babović Siniša S.

    2013-01-01

    Full Text Available Introduction. The immunohistochemical method was used to follow the expression of neuropeptide Y in the course of pre ischemia of the rat brain. The aim of the study was to define all the areas of expression of this protein, show their localization, their map of distribution and histological types. Material and Methods. All the sections of telencephalon, diencephalon and midbrain were studied in resistant, and transitory ischemia, which enabled us to observe the reaction of neurons to an ischemic attack or to repeated attacks. The mapping was done for all three proteins by introducing our results into the maps of rat brain atlas, George Paxinos, Charles Watson. Photographing and protein expression was done using Analysis program. Results. The results of this research show that there is a differens in reaction between the resistant and transitory ischemia groups of rats, especially in the caudoputamen, gyrus dentatus, corpus amygdaloideum, particularly in the medial nucleus. The mapping shows the reaction in caudoputamen, gyrusdentatus, corpus amygdaloideum - especially in the central nucleus, then in the sensitive and secondary auditory cortex, mostly in the laminae V/VI, but less in neuron groups CA1, CA2, CA3 of hippocampus. Discussion. The phylogenetically older parts of the brain-rhinencephalon, also showed reaction, which lead us to conclude that both newer and older brain structures reacted immunohistochemically. Histological data have shown that small neurons are most commonly found while the second most common ones are big pyramidal cells of multipolar and bipolar type, with a different body shape. Conclusion. Our findings have confirmed the results obtained in some rare studies dealing with this issue, and offered a precise and detailed map of cells expressing neuropeptide Y in the rat brain following ischemic attack.

  9. The dopaminergic system in the aging brain of Drosophila

    Directory of Open Access Journals (Sweden)

    Katherine E White

    2010-12-01

    Full Text Available Drosophila models of Parkinson’s disease are characterised by two principal phenotypes: the specific loss of dopaminergic neurons in the aging brain and defects in motor behavior. However, an age-related analysis of these baseline parameters in wildtype Drosophila is lacking. Here we analysed the dopaminergic system and motor behavior in aging Drosophila. Dopaminergic neurons in the adult brain can be grouped into bilateral symmetric clusters, each comprising a stereotypical number of cells. Analysis of TH>mCD8::GFP and cell type-specific MARCM clones revealed that dopaminergic neurons show cluster-specific, stereotypical projection patterns with terminal arborization in target regions that represent distinct functional areas of the adult brain. Target areas include the mushroom bodies, involved in memory formation and motivation, and the central complex, involved in the control of motor behavior, indicating that similar to the mammalian brain, dopaminergic neurons in the fly brain are involved in the regulation of specific behaviors. Behavioral analysis revealed that Drosophila show an age-related decline in startle-induced locomotion and negative geotaxis. Motion tracking however, revealed that walking activity and exploration behavior, but not centrophobism increase at late stages of life. Analysis of TH>Dcr2, mCD8::GFP revealed a specific effect of Dcr2 expression on walking activity but not on exploratory or centrophobic behavior, indicating that the siRNA pathway may modulate distinct dopaminergic behaviors in Drosophila. Moreover, dopaminergic neurons were maintained between early- and late life, as quantified by TH>mCD8::GFP and anti-TH labelling, indicating that adult onset, age-related degeneration of dopaminergic neurons does not occur in the aging brain of Drosophila. Taken together, our data establish baseline parameters in Drosophila for the study of Parkinson’s disease as well as other disorders affecting dopaminergic neurons

  10. 'When an old rat smells a cat': A decline in defense-related, but not accessory olfactory, Fos expression in aged rats.

    Science.gov (United States)

    Hunt, Glenn E; Van Nieuwenhuijzen, Petra S; Chan-Ling, Tailoi; McGregor, Iain S

    2011-04-01

    Comparisons were made between young (3-6 months) and aged (20-30 months) Wistar rats on locomotor activity, emergence, social interaction and cat odor avoidance. Aged rats were less active and spent less time in the open field during the emergence test than younger rats. Older rats also showed fewer contacts with a novel conspecific in the social interaction test, although total duration of interaction did not differ. There were very few behavioral differences between male and female rats. Older rats were less reactive than younger rats in a test of cat odor avoidance. However, they expressed similar amounts of cat odor-induced Fos in the posterior accessory olfactory bulb, a critical region for processing the predator odor stimulus. Older rats had reduced Fos expression in several defense-related brain regions that are normally activated by predator odors such as the medial amygdala and dorsal premammillary nucleus. These results indicate that aged rats are less reactive than younger rats to predator odors due to decreased responsiveness in defense-related but not necessarily olfactory circuits. PMID:19394115

  11. Changes of monoamine nervous transmitter and free radical met abolism in aged rats with gastrointestinal injury after brain ischemia reper fusion%脑缺血再灌注胃肠损伤老龄大鼠单胺类神经递质 和自由基代谢的变化

    Institute of Scientific and Technical Information of China (English)

    李建生; 赵君玫; 郭盛典; 李建国

    2001-01-01

    Objective: To study the mechanism of gastrointestinal injury after brain ischemia reperfusi on in aged rats from the changes of dopamine(DA),noradrenalin(NE),epinephrine(E) and the injury of free radical.Methods:Young(5months) and aged (20 months or more) rats were divided into young model group (YMG),young control group(YCG),aged model group (AMG),aged control group(ACG).The following items were measured in rats with 60 minute reperfusion after 30 minute brain ischemia:the pathological change of ga strointestinal tract:the activities of super-oxide dismutase(SOD),the contents of MDA,DA,NE,E. Results:The pathological change of gastrointestinal tract was found in the YMG and the AMG.The excitability of sympathetic-adrenal system was enhanced in the YMG and the AMG,this change in the AMG was serious compared w ith that in the YMG.The gastrointestinal MDA/SOD ratio was larger in the ACG and the YMG than that in the YCG.The stomach MDA/SOD ratio was larger in the AMG th an that in the ACG and the YMG.Conclusion: The gastrointestinal injury after brain ischemia rep erfusion in aged rats was correlated with the change of the enhanced excitabilit y of sympathetic-adrenal system and free radical injury.With aging these pathol ogical change were obvious and distinctive compared with that in the young rats.%目的:从多巴胺(DA)、去甲肾上腺素(NE)、肾上腺素(E)变化和自由基损伤方面揭示脑缺血再灌注胃肠损伤的机制。方法:青年(5月龄)和老龄(20月龄以上)大鼠均分为模型组和正常对照组,观察大鼠全脑缺血30 min再灌注60 min后胃肠损伤的病理改变和超氧化物岐化酶(SOD)的活性及丙二醛(MDA)、DA、NE、E含量。结果:青年和老龄模型组胃肠出现明显的病理改变。青年和老龄模型组交感-肾上腺系统兴奋性增强,其中老龄模型组较青年模型组大鼠严重。老龄对照组和青年模型组胃肠组织MDA/SOD比值高于青年对照组,

  12. Enhanced post-ischemic neurogenesis in aging rats

    Directory of Open Access Journals (Sweden)

    Yao-Fang Tan

    2010-08-01

    Full Text Available Hippocampal neurogenesis persists in adult mammals, but its rate declines dramatically with age. Evidence indicates that experimentally-reduced levels of neurogenesis (e.g. by irradiation in young rats has profound influence on cognition as determined by learning and memory tests. In the present study we asked whether in middle-aged, 10-13 months old rats, cell production can be restored towards the level present in young rats. To manipulate neurogenesis we induced bilateral carotid occlusion with hypotension. This procedure is known to increase neurogenesis in young rats, presumably in a compensatory manner, but until now, has never been tested in aging rats. Cell production was measured at 10, 35 and 90 days after ischemia. The results indicate that neuronal proliferation and differentiation can be transiently restored in middle-aged rats. Furthermore, the effects are more pronounced in the dorsal as opposed to ventral hippocampus thus restoring the dorso-ventral gradient seen in younger rats. Our results support previous findings showing that some of the essential features of the age-dependent decline in neurogenesis are reversible. Thus, it may be possible to manipulate neurogenesis and improve learning and memory in old age.

  13. Features of intervertebral disc degeneration in rat's aging process

    Institute of Scientific and Technical Information of China (English)

    Yin-gang ZHANG; Zheng-ming SUN; Jiang-tao LIU; Shi-jie WANG; Feng-ling REN; Xiong GUO

    2009-01-01

    Objective: The age-related change is important part of degenerative disc disease. However, no appropriate animal model or objective evaluation index is available. This study aimed to investigate the features of intervertebral disc degeneration in aging process of rats. Methods: 22-month-old Sprague-Dawley (SD) rats were used as spontaneously occurring intervertebral disc degeneration models and 6-month-old rats as young controls. Expression of collagen types Ⅱ and Ⅹ was measured by immunohistochemistry. Degenerations of intervertebral discs were scored according to Miyamoto's method. Numbers and areas of afferent vascular buds were measured. The thicknesses of non-calcified and calcified layers were measured and statistically analyzed.Results: There were less collagen type Ⅱ expression and more collagen type Ⅹ expression in the calcified layer of the cartilage endplates and nucleus pulposus in the rats of the aged group than in the young control. There were fewer and smaller afferent vascular buds in the rats of the aged group than in the young control group. The ratio of the non-calcified to the calcified layers in the rats of the aged group significantly decreased, compared with that of the young control group (P<0.01). Conclusion: Rats can spontaneously establish intervertebral disc age-related degeneration. The expression of collagen types Ⅱ and Ⅹ, numbers and areas of afferent vascular buds, the ratio of the non-calcified to the calcified layers, and water and glycosaminoglycan contents in the nucleus pulposus are sensitive indexes of intervertebral disc degeneration.

  14. Toluene effects on Oxidative Stress in Brain regions of Young-adult, Middleage,and Senescent Brown Norway Rats

    Science.gov (United States)

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound toluene. The objective was to test whether oxidative stress plays a role in the adver...

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

    Science.gov (United States)

    Luders, Eileen; Cherbuin, Nicolas; Gaser, Christian

    2016-07-01

    Normal aging is known to be accompanied by loss of brain substance. The present study was designed to examine whether the practice of meditation is associated with a reduced brain age. Specific focus was directed at age fifty and beyond, as mid-life is a time when aging processes are known to become more prominent. We applied a recently developed machine learning algorithm trained to identify anatomical correlates of age in the brain translating those into one single score: the BrainAGE index (in years). Using this validated approach based on high-dimensional pattern recognition, we re-analyzed a large sample of 50 long-term meditators and 50 control subjects estimating and comparing their brain ages. We observed that, at age fifty, brains of meditators were estimated to be 7.5years younger than those of controls. In addition, we examined if the brain age estimates change with increasing age. While brain age estimates varied only little in controls, significant changes were detected in meditators: for every additional year over fifty, meditators' brains were estimated to be an additional 1month and 22days younger than their chronological age. Altogether, these findings seem to suggest that meditation is beneficial for brain preservation, effectively protecting against age-related atrophy with a consistently slower rate of brain aging throughout life. PMID:27079530

  16. Daily supplementation with mushroom (Agaricus bisporus) improves balance and working memory in aged rats.

    Science.gov (United States)

    Thangthaeng, Nopporn; Miller, Marshall G; Gomes, Stacey M; Shukitt-Hale, Barbara

    2015-12-01

    Decline in brain function during normal aging is partly due to the long-term effects of oxidative stress and inflammation. Several fruits and vegetables have been shown to possess antioxidant and anti-inflammatory properties. The present study investigated the effects of dietary mushroom intervention on mobility and memory in aged Fischer 344 rats. We hypothesized that daily supplementation of mushroom would have beneficial effects on behavioral outcomes in a dose-dependent manner. Rats were randomly assigned to receive a diet containing either 0%, 0.5%, 1%, 2%, or 5% lyophilized white button mushroom (Agaricus bisporus); after 8 weeks on the diet, a battery of behavioral tasks was given to assess balance, coordination, and cognition. Rats on the 2% or 5% mushroom-supplemented diet consumed more food, without gaining weight, than rats in the other diet groups. Rats in the 0.5% and 1% group stayed on a narrow beam longer, indicating an improvement in balance. Only rats on the 0.5% mushroom diet showed improved performance in a working memory version of the Morris water maze. When taken together, the most effective mushroom dose that produced improvements in both balance and working memory was 0.5%, equivalent to about 1.5 ounces of fresh mushrooms for humans. Therefore, the results suggest that the inclusion of mushroom in the daily diet may have beneficial effects on age-related deficits in cognitive and motor function. PMID:26475179

  17. Huayu capsule enhances limb-catching capability of rats with experimental open traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Chunyang Zhou; Juan Zhang; Yong Wang; Haibing Qian; Li Gong; Guojun Huang

    2007-01-01

    BACKGROUND: It is hard to cure the open traumatic brain injury (TBI), especially for the brain functional recovery after brain injury. In this regard, traditional Chinese medicine (TCM) has a wide prospect.OBJECTIVE: To observe the effect of Huayu capsule on limb-catching capability of rat models of open TBI,and investigate its possible mechanism.DESIGN: Randomized and controlled study.SETTING: Grade 3 Pharmacological Laboratory of TCM, State Administration of TCM, Chengdu University of TCM.MATERIALS: This study was performed from October 2005 to January 2006. Fifty Sprague-Dawley rats of either gender, aged 3 months old, weighing from 190 to 220 g, were involved in this study. Huayu capsule was made and supplied by the Department of TCM Processing of Chengdu University of TCM, Lot No.050121; Xuefuzhuyu oral liquid was manufactured by Jilin Aodong Yanbian Pharmaceutical Industry Co.,Ltd., Lot No. 050406.METHODS: Open right parietal lobe TBI rat models were made as described in references. The involved rat models were randomized into 5 groups according to gender and body mass: model group, high-, middle-,low-dose Huayu capsule groups and Xuefuzhuyu oral liquid group, with 10 rats in each. Rats in the model group were administrated with distilled water of 5 mL/kg; Rats in the high-, middle- and low-dose Huayu capsule groups were administrated with 1.030, 0.515, 0.258 g/kg raw herbs; Rats in the Xuefuzhuyu oral liquid group were administrated with Xuefuzhuyu oral liquid of 5 mL/kg, intragastrically once a day for 7 days successively for all after recovering consciousness from anesthetization. ① One hour after administration on the 6th day, rats in each group were placed on a 100 cm fine straight iron wire paralleling to the ground and 20 cm above the operational table. The time of the rats keeping on the wire was counted and it indicated the nerve-muscle catching capability. The longer the remained time, the better the nerve-muscle catching capability.② Twenty

  18. A brain network processing the age of faces.

    Directory of Open Access Journals (Sweden)

    György A Homola

    Full Text Available Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships.

  19. Identification and culture of neural stem cells isolated from adult rat subventricular zone following fluid percussion brain injury

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To analyze proliferation and differentiation of glial fibrillary acid protein(GFAP)-and nestin-positive(GFAP+/nestin+)cells isolated from the subventricular zone following fluid percussion brain injury to determine whether GFAP+/nestin+ cells exhibit characteristics of neural stem cells.Methods Male Sprague-Dawley rats,aged 12 weeks and weighing 200-250 g,were randomly and evenly assigned to normal control group and model group.In the model group,a rat model of fluid percussion brain injury was es...

  20. The Function of the Glutamate-Nitric Oxide-cGMP Pathway in Brain in Vivo and Learning Ability Decrease in Parallel in Mature Compared with Young Rats

    Science.gov (United States)

    Piedrafita, Blanca; Cauli, Omar; Montoliu, Carmina; Felipo, Vicente

    2007-01-01

    Aging is associated with cognitive impairment, but the underlying mechanisms remain unclear. We have recently reported that the ability of rats to learn a Y-maze conditional discrimination task depends on the function of the glutamate-nitric oxide-cGMP pathway in brain. The aims of the present work were to assess whether the ability of rats to…

  1. Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.

    Science.gov (United States)

    Allagui, M S; Feriani, A; Saoudi, M; Badraoui, R; Bouoni, Z; Nciri, R; Murat, J C; Elfeki, A

    2014-08-01

    This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8-arms maze' tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS).

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

    Directory of Open Access Journals (Sweden)

    Motoyama Caio SM

    2011-09-01

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

  3. Intrinsic brain connectivity related to age in young and middle aged adults.

    Directory of Open Access Journals (Sweden)

    Michelle Hampson

    Full Text Available Age-related variations in resting state connectivity of the human brain were examined from young adulthood through middle age. A voxel-based network measure, degree, was used to assess age-related differences in tissue connectivity throughout the brain. Increases in connectivity with age were found in paralimbic cortical and subcortical regions. Decreases in connectivity were found in cortical regions, including visual areas and the default mode network. These findings differ from those of recent developmental studies examining earlier growth trajectories, and are consistent with known changes in cognitive function and emotional processing during mature aging. The results support and extend previous findings that relied on a priori definitions of regions of interest for their analyses. This approach of applying a voxel-based measure to examine the functional connectivity of individual tissue elements over time, without the need for a priori region of interest definitions, provides an important new tool in brain science.

  4. Effects of NOS inhibitor on dentate gyrus neurogenesis after diffuse brain injury in the adult rats

    Institute of Scientific and Technical Information of China (English)

    SunLi-Sha; XuJiang-ping

    2004-01-01

    Objective To investigate the effects of selective nitric oxide synthase (NOS) inhibitors on dentate gyrus neurogenesis after diffuse brain injury (DBI) in the adult rat brain. Methods Adult male SD rats were subjected to diffuse brain injury (DBI) model. By using systemic bromodeoxyuridine (BrdU) to label dividing cells, we compared the proliferation rate of

  5. Efficacy of Female Rat Models in Translational Cardiovascular Aging Research

    Directory of Open Access Journals (Sweden)

    K. M. Rice

    2014-01-01

    Full Text Available Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. This review addresses the systemic pathophysiology of the cardiovascular system associated with aging and gender for aging research with regard to the applicability of rat derived data for translational application to human aging.

  6. Brain plasticity of rats exposed to prenatal immobilization stress

    OpenAIRE

    Badalyan B. Yu.; Tumasyan N. V.; Meliksetyan I. B.; Sahakyan I. K.; Abrahamyan S. S.; Galoyan A. A.

    2011-01-01

    Aim. This histochemical and immunohistochemical study was aimed at examining the brain cellular structures of newborn rats exposed to prenatal immobilization (IMO) stress. Methods. Histochemical method on detection of Ca2+-dependent acid phosphatase activity and ABC immunohistochemical technique. Results. Cell structures with radial astrocytes marker GFAP, neuroepithelial stem cell marker gene nestin, stem-cells marker and the hypothalamic neuroprotective proline-rich polypeptide PRP-1 (Galar...

  7. [Effect of phenibut on interhemispheric transmission in the rat brain].

    Science.gov (United States)

    Borodkina, L E; Molodavkin, G M; Tiurenkov, I N

    2009-01-01

    Effects of the nootropic drug phenibut on the transcallosal potential amplitude in the sensomotor brain cortex have been studied in rats. It is established that a single administration of phenibut in a dose of 25 mg/kg (i.p.) increases the transcallosal response amplitude, thus improving the interhemispheric transmission. This effect, being an objective evidence of the nootrope activity, confirms the drug status and corroborates the positive action of phenibut on the learning and memory processes. PMID:19334513

  8. Regional distribution of SGLT activity in rat brain in vivo

    OpenAIRE

    Yu, Amy S.; Hirayama, Bruce A.; Timbol, Gerald; Liu, Jie; Diez-Sampedro, Ana; Kepe, Vladimir; Satyamurthy, Nagichettiar; Huang, Sung-Cheng; Wright, Ernest M.; Barrio, Jorge R.

    2012-01-01

    Na+-glucose cotransporter (SGLT) mRNAs have been detected in many organs of the body, but, apart from kidney and intestine, transporter expression, localization, and functional activity, as well as physiological significance, remain elusive. Using a SGLT-specific molecular imaging probe, α-methyl-4-deoxy-4-[18F]fluoro-d-glucopyranoside (Me-4-FDG) with ex vivo autoradiography and immunohistochemistry, we mapped in vivo the regional distribution of functional SGLTs in rat brain. Since Me-4-FDG ...

  9. Effects of magnesium sulfate on brain mitochondrial respiratory function in rats after experimental traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    许民辉; 代文光; 邓洵鼎

    2002-01-01

    Objective: To study the effects of magnesium sulfate on brain mitochondrial respiratory function in rats after experimental traumatic brain injury and the possible mechanism.Methods: The middle degree brain injury in rats was made by BIM-III multi-function impacting machine. The brain mitochondrial respiratory function was measured with oxygen electrode and the ultra-structural changes were observed with transmission electron microscope (TEM).Results: 1. The brain mitochondrial respiratory stage III and respiration control rate reduced significantly in the untreated groups within 24 and 72 hours. But treated Group A showed certain degree of recovery of respiratory function; treated Group B showed further improvement. 2. Untreated Group, treated Groups A and B had different degrees of mitochondrial ultra-structural damage respectively, which could be attenuated after the treatment with magnesium sulfate.Conclusions: The mitochondrial respiratory function decreases significantly after traumatic brain injury. But it can be apparently improved after magnesium sulfate management along with the attenuated damage of mitochondria discovered by TEM. The longer course of treatment can obtain a better improvement of mitochondrial respiratory function.

  10. Multiple opiate receptors in the brain of spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Das, S.; Bhargava, H.N.

    1986-03-01

    The characteristics of ..mu.., delta and kappa -opiate receptors in the brain of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats were determined using the receptor binding assays. The ligands used were /sup 3/H-naltrexone (..mu..), /sup 3/H-ethylketocyclazocine (EKC, kappa) and /sup 3/H-Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta). Since EKC binds to ..mu.. and delta receptors in addition to kappa, the binding was done in the presence of 100 nM each of DAGO and DADLE to suppress ..mu.. and delta sites, respectively. All three ligands bound to brain membranes of WKY rats at a single high affinity site with the following B/sub max/ (fmol/mg protein) and K/sub d/ (nM) values: /sup 3/H-naltrexone (130.5; 0.43) /sup 3/H-EKC (19.8, 1.7) and /sup 3/H-DSTLE (139, 2.5). The binding of /sup 3/H-naltrexone and /sup 3/H-DSTLE in the brain of WKY and SH did not differ. A consistent increase (22%) in B/sub max/ of /sup 3/H-EKC was found in SHR compared to WKY rats. However, the K/sub d/ values did not differ. The increase in B/sub max/ was due to increases in hypothalamus and cortex. It is concluded that SH rats have higher density of kappa-opiate receptors, particularly in hypothalamus and cortex, compared to WKY rats, and that kappa-opiate receptors may be involved in the pathophysiology of hypertension.

  11. Evolution of the aging brain transcriptome and synaptic regulation.

    Directory of Open Access Journals (Sweden)

    Patrick M Loerch

    Full Text Available Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4. However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes.

  12. Marrow stromal cells administrated intracisternally to rats after traumatic brain injury migrate into the brain and improve neurological function

    Institute of Scientific and Technical Information of China (English)

    胡德志; 周良辅; 朱剑虹

    2004-01-01

    @@ Marrow stromal cells(MSCs) have been reported to transplant into injured brain via intravenous or intraarterial or direct intracerebral administration.1-3 In the present study, we observed that MSCs migrated into the brain, survived and diffeneriated into neural cells after they were injected into the cisterna magna of rats, and that the behavior of the rats after traumatic brain injury (TBI) was improved.

  13. Alpha oscillatory correlates of motor inhibition in the aged brain

    Directory of Open Access Journals (Sweden)

    Marlene eBoenstrup

    2015-10-01

    Full Text Available Exerting inhibitory control is a cognitive ability mediated by functions known to decline with age. The goal of this study is to add to the mechanistic understanding of cortical inhibition during motor control in aged brains. Based on behavioral findings of impaired inhibitory control with age we hypothesized that elderly will show a reduced or a lack of EEG alpha-power increase during tasks that require motor inhibition. Since inhibitory control over movements has been shown to rely on prior motor memory formation, we investigated cortical inhibitory processes at two points in time - early after learning and after an overnight consolidation phase and hypothesized an overnight increase of inhibitory capacities. Young and elderly participants acquired a complex finger movement sequence and in each experimental session brain activity during execution and inhibition of the sequence was recorded with multi-channel EEG. We assessed cortical processes of sustained inhibition by means of task-induced changes of alpha oscillatory power. During inhibition of the learned movement, young participants showed a significant alpha power increase at the sensorimotor cortices whereas elderly did not. Interestingly, for both groups, the overnight consolidation phase improved up-regulation of alpha power during sustained inhibition. This points to deficits in the generation and enhancement of local inhibitory mechanisms at the sensorimotor cortices in aged brains. However, the alpha power increase in both groups implies neuroplastic changes that strengthen the network of alpha power generation over time in young as well as elderly brains.

  14. Brain-Based Teaching in the Digital Age

    Science.gov (United States)

    Sprenger, Marilee

    2010-01-01

    In the digital age, your students have the ways, means, and speed to gather any information they want. But they need your guidance more than ever. Discover how digital technology is actually changing your students' brains. Learn why this creates new obstacles for teachers, but also opens up potential new pathways for learning. You will understand…

  15. Carbofuran Modulating Functions of Acetylcholinesterase from Rat Brain In Vitro

    Directory of Open Access Journals (Sweden)

    Vivek Kumar Gupta

    2016-01-01

    Full Text Available Carbofuran, a potential environmental xenobiotic, has the ability to cross blood brain barrier and to adversely influence brain functions. In the present study, the impact of carbofuran on the biophysical and biochemical properties of rat brain AChE has been evaluated in vitro. This enzyme was membrane-bound which could be solubilised using Triton-X100 (0.2%, v/v, a nonionic detergent, in the extraction buffer (50 mM phosphate, pH 7.4. The enzyme was highly stable up to one month when stored at -20°C and exhibited optimum activity at pH 7.4 and 37°C. AChE displayed a direct relationship between activity and varying substrate concentrations (acetylthiocholine iodide (ATI by following Michaelis-Menten curve. The Km and Vmax values as computed from the Lineweaver-Burk double reciprocal plot of the data were found to be 0.07 mM and 0.066 µmole/mL/min, respectively. The enzyme exhibited IC50 value for carbofuran equal to 6.0 nM. The steady-state kinetic studies to determine mode of action of carbofuran on rat brain AChE displayed it to be noncompetitive in nature with Ki value equal to 5 nm. These experiments suggested that rat brain AChE was very sensitive to carbofuran and this enzyme might serve as a significant biomarker of carbofuran induced neurotoxicity.

  16. Oxymatrine reduces neuroinflammation in rat brain A signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Jiahui Mao; Yae Hu; Ailing Zhou; Bing Zheng; Yi Liu; Yueming Du; Jia Li; Jinyang Lu; Pengcheng Zhou

    2012-01-01

    Cerebral neuroinflammation models were established by injecting 10 μg lipopolysaccharide into the hippocampus of male Sprague-Dawley rats.The rats were treated with an intraperitoneal injection of 120,90,or 60 mg/kg oxymatrine daily for three days prior to the lipopolysaccharide injection.Twenty-four hours after model induction,the hippocampus was analyzed by real-time quantitative PCR,and the cerebral cortex was analyzed by enzyme-linked immunosorbent assay and western blot assay.The results of the enzyme-linked immunosorbent assay and the real-time quantitative PCR showed that the secretion and mRNA expression of the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α were significantly decreased in the hippocampus and cerebral cortex of model rats treated with oxymatrine.Western blot assay and real-time quantitative PCR analysis indicated that toll-like receptor 4 mRNA and protein expression were significantly decreased in the groups receiving different doses of oxymatrine.Additionally,120 and 90 mg/kg oxymatrine were shown to reduce protein levels of nuclear factor-kB p65 in the nucleus and of phosphorylated IkBα in the cytoplasm of brain cells,as detected by western blot assay.Experimental findings indicate that oxymatrine may inhibit neuroinflammation in rat brain via downregulating the expression of molecules in the toll-like receptor 4/nuclear factor-kB signaling pathway.

  17. Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury.

    Science.gov (United States)

    Das, Mahasweta; Wang, Chunyan; Bedi, Raminder; Mohapatra, Shyam S; Mohapatra, Subhra

    2014-10-01

    Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CP-mag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM-tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 h after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI. From the clinical editor: In this study, chitosan and PEI-coated magnetic micelles (CPMM) were demonstrated as potentially useful vehicles in traumatic brain injury in a rodent model. Magnetofection increased the concentration of CPMMs in the brain and, after intranasal delivery, CPMM did not evoke any inflammatory response and were excreted from the body. PMID:24486465

  18. Effect of Zhuang Jing Decoction on Learning and Memory Ability in Aging Rats.

    Science.gov (United States)

    Cai, Hao-Bin; Wu, Guang-Liang; Huang, Cen-Han; Huang, Zhong-Shi; Chen, Yun-Bo; Wang, Qi

    2016-08-01

    With the average life span of humans on the rise, aging in the world has drawn considerable attentions. The monoamine neurotransmitters and neurotrophic factors in brain areas are involved in learning and memory processes and are an essential part of normal synaptic neurotransmission and plasticity. In the present study, the effect of Zhuang Jing Decoction (ZJD) on the learning and memory ability in aging rats was examined in vivo using Morris water maze. Furthermore, the levels of monoamine neurotransmitters and neurotrophic factors in brain were detected by high-performance liquid chromatography with a fluorescence detector and enzyme-linked immunosorbent assay, respectively. These data showed that oral administration with ZJD at the dose of 30 g·kg(-1) exerted an improved effect on learning and memory ability in aging rats. The results revealed that ZJD could effectively adjust the monoamine neurotransmitters and neurotrophic factors, restore the balance of the level of monoamine neurotransmitters and neurotrophic factors in brain, and finally attenuate the degeneration of learning and memory ability. These findings suggested that ZJD might be a potential agent as cognitive-enhancing drug in improving learning and memory ability. It may exert through regulating the levels of monoamine neurotransmitters and neurotrophic factors in brain, which demonstrated that ZJD had certain antiaging effects. PMID:26649780

  19. Relationship between Morphofunctional Changes in Open Traumatic Brain Injury and the Severity of Brain Damage in Rats.

    Science.gov (United States)

    Shakova, F M; Barskov, I V; Gulyaev, M V; Prokhorenko, S V; Romanova, G A; Grechko, A V

    2016-07-01

    A correlation between the severity of morphofunctional disturbances and the volume of brain tissue injury determined by MRT was demonstrated on the model of open traumatic brain injury in rats. A relationship between the studied parameters (limb placing and beam walking tests and histological changes) and impact force (the height of load fell onto exposed brain surface) was revealed.

  20. Aging and Gene Expression in the Primate Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.; Paabo, Svante; Eisen, Michael B.

    2005-02-18

    It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  1. Aging and gene expression in the primate brain.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  2. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats.

    Science.gov (United States)

    Zhao, Jinbing; Chen, Zhi; Xi, Guohua; Keep, Richard F; Hua, Ya

    2014-10-01

    Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron levels in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. This study was to determine whether or not iron has a role in hydrocephalus development after TBI. TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some rats had intraventricular injection of iron. Acute hydrocephalus was measured by magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2* gradient-echo sequence imaging and brain hemoglobin levels. The effect of deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute hydrocephalus at 24 h (lateral ventricle volume: 24.1 ± 3.0 vs. 9.9 ± 0.2 mm(3) in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm(3) in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI.

  3. Photoacoustic imaging for transvascular drug delivery to the rat brain

    Science.gov (United States)

    Watanabe, Ryota; Sato, Shunichi; Tsunoi, Yasuyuki; Kawauchi, Satoko; Takemura, Toshiya; Terakawa, Mitsuhiro

    2015-03-01

    Transvascular drug delivery to the brain is difficult due to the blood-brain barrier (BBB). Thus, various methods for safely opening the BBB have been investigated, for which real-time imaging methods are desired both for the blood vessels and distribution of a drug. Photoacoustic (PA) imaging, which enables depth-resolved visualization of chromophores in tissue, would be useful for this purpose. In this study, we performed in vivo PA imaging of the blood vessels and distribution of a drug in the rat brain by using an originally developed compact PA imaging system with fiber-based illumination. As a test drug, Evans blue (EB) was injected to the tail vein, and a photomechanical wave was applied to the targeted brain tissue to increase the permeability of the blood vessel walls. For PA imaging of blood vessels and EB distribution, nanosecond pulses at 532 nm and 670 nm were used, respectively. We clearly visualized blood vessels with diameters larger than 50 μm and the distribution of EB in the brain, showing spatiotemporal characteristics of EB that was transvascularly delivered to the target tissue in the brain.

  4. Greater glucocorticoid receptor activation in hippocampus of aged rats sensitizes microglia.

    Science.gov (United States)

    Barrientos, Ruth M; Thompson, Vanessa M; Kitt, Meagan M; Amat, Jose; Hale, Matthew W; Frank, Matthew G; Crysdale, Nicole Y; Stamper, Christopher E; Hennessey, Patrick A; Watkins, Linda R; Spencer, Robert L; Lowry, Christopher A; Maier, Steven F

    2015-03-01

    Healthy aging individuals are more likely to suffer profound memory impairments following an immune challenge than are younger adults. These challenges produce a brain inflammatory response that is exaggerated with age. Sensitized microglia found in the normal aging brain are responsible for this amplified response, which in turn interferes with processes involved in memory formation. Here, we examine factors that may lead aging to sensitize microglia. Aged rats exhibited higher corticosterone levels in the hippocampus, but not in plasma, throughout the daytime (diurnal inactive phase). These elevated hippocampal corticosterone levels were associated with increased hippocampal 11β-hydroxysteroid dehydrogenase type 1 protein expression, the enzyme that catalyzes glucocorticoid formation and greater hippocampal glucocorticoid receptor (GR) activation. Intracisternal administration of mifepristone, a GR antagonist, effectively reduced immune-activated proinflammatory responses, specifically from hippocampal microglia and prevented Escherichia coli-induced memory impairments in aged rats. Voluntary exercise as a therapeutic intervention significantly reduced total hippocampal GR expression. These data strongly suggest that increased GR activation in the aged hippocampus plays a critical role in sensitizing microglia.

  5. Detecting Behavioral Deficits Post Traumatic Brain Injury in Rats.

    Science.gov (United States)

    Awwad, Hibah O

    2016-01-01

    Traumatic brain injury (TBI), ranging from mild to severe, almost always elicits an array of behavioral deficits in injured subjects. Some of these TBI-induced behavioral deficits include cognitive and vestibulomotor deficits as well as anxiety and other consequences. Rodent models of TBI have been (and still are) fundamental in establishing many of the pathophysiological mechanisms of TBI. Animal models are also utilized in screening and testing pharmacological effects of potential therapeutic agents for brain injury treatment. This chapter details validated protocols for each of these behavioral deficits post traumatic brain injury in Sprague-Dawley male rats. The elevated plus maze (EPM) protocol is described for assessing anxiety-like behavior; the Morris water maze protocol for assessing cognitive deficits in learning memory and spatial working memory and the rotarod test for assessing vestibulomotor deficits. PMID:27604739

  6. Age-dependent complex noise fluctuations in the brain

    International Nuclear Information System (INIS)

    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/fλ 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)

  7. Relationships between choline acetyl-transferase and muscarinic binding in aging rodent brain and in Alzheimers disease

    International Nuclear Information System (INIS)

    This paper examines how the relation between ChAT and muscarinic binding might be affected by aging in mouse and rat brains. Preliminary data are presented regarding this relation in postmortem cerebral cortex samples from human subjects who died with Alzheimer's disease (AD) and from age-matched controls. The effect of acetyl coenzme A (1- C 14-acetyl coenzyme A concentration on enzyme activity was determined by varying the concentration of the coenzyme in the assay medium. Assays of muscarinic binding were performed on tissue sonicates diluted with Tris-HC1 buffer using tritium-quinuclidinyl benzilate tritium-QNB as the ligand. For brain regions obtained from rats, significance of age differences were assessed by one-way analysis of variance and Bonferroni t statistics. Differences in ChAT activity and binding site density from human postmortem samples between diagnostic groups were assessed separately by region using an analysis of covariance

  8. Brain energy metabolism and blood flow differences in healthy aging

    DEFF Research Database (Denmark)

    Aanerud, Joel; Borghammer, Per; Chakravarty, M Mallar;

    2012-01-01

    Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO(2) during normal aging are still controversial, as some authors...... years. The magnitudes of CMRO(2) and CBF declined in large parts of the cerebral cortex, including association areas, but the primary motor and sensory areas were relatively spared. We found significant increases of OEF in frontal and parietal cortices, excluding primary motor and somatosensory regions......, and in the temporal cortex. Because of the inverse relation between OEF and capillary oxygen tension, increased OEF can compromise oxygen delivery to neurons, with possible perturbation of energy turnover. The results establish a possible mechanism of progression from healthy to unhealthy brain aging, as the regions...

  9. Long-term BPA infusions. Evaluation in the rat brain tumor and rat spinal cord models

    Energy Technology Data Exchange (ETDEWEB)

    Coderre, J.A.; Micca, P.L.; Nawrocky, M.M.; Joel, D.D. [Brookhaven National Laboratory, Medical Department, Upton, NY (United States); Morris, G.M. [University of Oxford, Research Institute, Oxford (United Kingdom)

    2000-10-01

    In the BPA-based dose escalation clinical trial, the observations of tumor recurrence in areas of extremely high calculated tumor doses suggest that the BPA distribution is non-uniform. Longer (6-hour) i.v. infusions of BPA are evaluated in the rat brain tumor and spinal cord models to address the questions of whether long-term infusions are more effective against the tumor and whether long-term infusions are detrimental in the central nervous system. In the rat spinal cord, the 50% effective doses (ED{sub 50}) for myeloparesis were not significantly different after a single i.p. injection of BPA-fructose or a 6 hour i.v. infusion. In the rat 9L gliosarcoma brain tumor model, BNCT following 2-hr or 6-hr infusions of BPA-F produced similar levels of long term survival. (author)

  10. Long-term BPA infusions. Evaluation in the rat brain tumor and rat spinal cord models

    International Nuclear Information System (INIS)

    In the BPA-based dose escalation clinical trial, the observations of tumor recurrence in areas of extremely high calculated tumor doses suggest that the BPA distribution is non-uniform. Longer (6-hour) i.v. infusions of BPA are evaluated in the rat brain tumor and spinal cord models to address the questions of whether long-term infusions are more effective against the tumor and whether long-term infusions are detrimental in the central nervous system. In the rat spinal cord, the 50% effective doses (ED50) for myeloparesis were not significantly different after a single i.p. injection of BPA-fructose or a 6 hour i.v. infusion. In the rat 9L gliosarcoma brain tumor model, BNCT following 2-hr or 6-hr infusions of BPA-F produced similar levels of long term survival. (author)

  11. Consequences of nicotine exposure during different phases of rat brain development.

    Science.gov (United States)

    Khanna Sood, Pooja; Sharma, Sonika; Nehru, Bimla

    2012-08-01

    Nicotine is a psychoactive drug whose intensity of the addiction is so tremendous that it is now the fastest growing public health hazard in the world. The present study was designed to study the toxic effects of nicotine during different phases of rat brain development. The study is extended through adult brain designated as group A, that received nicotine at the dosage of 5 mg/kg of b.wt. for 21 days and were sacrificed following 21 days of recovery. In the second group P, pups in different gestational phases (P2-P4) were given maternal nicotine exposures for only a period of 7 days followed by recovery till they had achieved the age of 40 days. A significant decrease in long term memory was observed in adult rats which correlated well with a significant decrease in the acetylcholine esterase activity. Simultaneously a significant decrease in the total glutathione, GSH content and catalase activity was observed which could account for the increase in peroxidation of lipids as evaluated by malondialdehyde (MDA) content in the nicotine exposed adult rats. The consequences of maternal nicotine exposure were different during different exposures regimes the alterations were least during the early gestation period, i.e. P2 (2-9 days of their gestation period) as compared to P3 (7-14 days of their gestation period) and P4 (21 days of their weanling period). The study indicates that the consequences of nicotine exposure are varied during different stages of brain development. PMID:22169521

  12. Cerebrolysin improves memory and ameliorates neuronal atrophy in spontaneously hypertensive, aged rats.

    Science.gov (United States)

    Solis-Gaspar, Carlos; Vazquez-Roque, Ruben A; De Jesús Gómez-Villalobos, Ma; Flores, Gonzalo

    2016-09-01

    The spontaneously hypertensive (SH) rat has been used as an animal model of vascular dementia (VD). Our previous report showed that, SH rats exhibited dendritic atrophy of pyramidal neurons of the CA1 dorsal hippocampus and layers 3 and 5 of the prefrontal cortex (PFC) at 8 months of age. In addition, we showed that cerebrolysin (Cbl), a neurotrophic peptide mixture, reduces the dendritic atrophy in aged animal models. This study aimed to determine whether Cbl was capable of reducing behavioral and neuronal alterations, in old female SH rats. The level of diastolic and systolic pressure was measured every month for the 6 first months and only animals with more than 160 mm Hg of systolic pressure were used. Female SH rats (6 months old) received 6 months of Cbl treatment. Immediately after the Cbl treatment, two behavioral tests were applied, the Morris water maze test for memory and learning and locomotor activity in novel environments. Immediately after the last behavioral test, dendritic morphology was studied with the Golgi-Cox stain procedure followed by a Sholl analysis. Clearly, SH rats with Cbl showed an increase in the dendritic length and dendritic spine density of pyramidal neurons in the CA1 in the dorsal hippocampus and layers 3 and 5 of the PFC. Interestingly, Cbl improved memory of the old SH rats. Our results support the possibility that Cbl may have beneficial effects on the management of brain alterations in an animal model with VD. Synapse 70:378-389, 2016. © 2016 Wiley Periodicals, Inc.

  13. Light-sheet microscopy imaging of a whole cleared rat brain with Thy1-GFP transgene

    OpenAIRE

    Marzena Stefaniuk; Gualda, Emilio J.; Monika Pawlowska; Diana Legutko; Paweł Matryba; Paulina Koza; Witold Konopka; Dorota Owczarek; Marcin Wawrzyniak; Pablo Loza-Alvarez; Leszek Kaczmarek

    2016-01-01

    Whole-brain imaging with light-sheet fluorescence microscopy and optically cleared tissue is a new, rapidly developing research field. Whereas successful attempts to clear and image mouse brain have been reported, a similar result for rats has proven difficult to achieve. Herein, we report on creating novel transgenic rat harboring fluorescent reporter GFP under control of neuronal gene promoter. We then present data on clearing the rat brain, showing that FluoClearBABB was found superior ove...

  14. Resveratrol attenuates peripheral and brain inflammation and reduces ischemic brain injury in aged female mice.

    Science.gov (United States)

    Jeong, Sae Im; Shin, Jin A; Cho, Sunghee; Kim, Hye Won; Lee, Ji Yoon; Kang, Jihee Lee; Park, Eun-Mi

    2016-08-01

    Resveratrol is known to improve metabolic dysfunction associated with obesity. Visceral obesity is a sign of aging and is considered a risk factor for ischemic stroke. In this study, we investigated the effects of resveratrol on inflammation in visceral adipose tissue and the brain and its effects on ischemic brain injury in aged female mice. Mice treated with resveratrol (0.1 mg/kg, p.o.) for 10 days showed reduced levels of interleukin-1β and tumor necrosis factor-α, as well as a reduction in the size of adipocytes in visceral adipose tissue. Resveratrol also reduced interleukin-1β and tumor necrosis factor-α protein levels and immunoglobulin G extravasation in the brain. Mice treated with resveratrol demonstrated smaller infarct size, improved neurological function, and blunted peripheral inflammation at 3 days postischemic stroke. These results showed that resveratrol counteracted inflammation in visceral adipose tissue and in the brain and reduced stroke-induced brain injury and peripheral inflammation in aged female mice. Therefore, resveratrol administration can be a valuable strategy for the prevention of age-associated and disease-provoked inflammation in postmenopausal women. PMID:27318135

  15. Antioxidant Role of Pomegranates on Liver and Brain Tissues of Rats Exposed to an Organophosphorus Insecticide

    International Nuclear Information System (INIS)

    Toxicities of organophosphorus insecticides cause oxidative damage on many organs such as the liver and brain due to generation of reactive oxygen species. Pomegranate is among the richest fruit in poly - phenols. The aim of this study was to compare between the antioxidant strength of pomegranate juice (PJ) and pomegranate molasses (PM) and their effects on alanine transferase (ALT), aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and total protein (TP) in liver and levels of malondialdehyde (MAD), reduced glutathione (GSH) and nitric oxide (NO) in rat liver and brain tissues exposed to 1/10 LD 50 diazinon (DI). Six groups each of 6 male albino rats were used comprising control, DI, PJ, PM, PJ + DI and PM + DI for 15 days. The activities of ALT, AST, and TP concentration in liver have been increased due to treatment of rats with DI. These increases restored to normalcy when rats were supplemented with PJ or PM with DI. The results demonstrate that treatment with DI induced significant increase in MDA and NO concentrations and significant decrease in GSH levels of liver and brain tissues. The administration of PJ or PM along with DI significant decrease in MDA and NO levels and significant increase in GSH level compared to DI-group. The present study suggest that PJ or PM has a potential protective effect as it can elevate antioxidant defense system, lessens induced oxidative dam - ages and protect the brain and liver tissue against DI-induced toxicity. In addition, comaring PJ with PM it was noticed that PJ had higher antioxidant activity as evidenced by increased GSH content and decreased NO level in the liver by greater extend than PM.

  16. Elemental distribution in brain of wistar rats by X-ray microfluorescence with synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Serpa, Renata F.B.; Jesus, Edgar F.O. de; Lopes, Ricardo T. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia. Lab. de Instrumentacao Nuclear]. E-mail: renata@lin.ufrj.br; Anjos, Marcelino J. dos; Oliveira, Luis F. de [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Fisica]. E-mail: marcelin@lin.ufrj.br; Carmo, Maria da Graca T. do [Universidade Federal, Rio de Janeiro, RJ (Brazil). Inst. de Nutricao]. E-mail: tcarmo@editema.com.br; Rocha, Monica S. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Dept. de Farmacologia]. E-mail: mrocha@farmaco.ufrj.br; Moreira, Silvana [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Engenharia Civil]. E-mail: silvana@fec.unicamp.br; Correa Junior, Jose D.; Martinez, Ana Maria B. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Dept. de Histologia]. E-mail: martinez@histo.ufrj.br

    2005-07-01

    The main goal of this research is to study the changes in the elemental distribution in brain rats, due the knowledge of the spatial distribution and the local concentration of trace elements in tissues have great importance since trace elements are involved in many biological functions of living organisms. For perform this research, Wistar rats with different ages (3, 48 and 72 weeks) were used. The microfluorescence measurements were carried out in a standard geometry of 45 deg/45 deg, exciting with a white beam and using a conventional system collimation (orthogonal slits) in the XRF beamline at the Synchrotron Light National Laboratory (Campinas, Brazil). The following elements were studied: P, S, Cl, K, Ca, Fe, and Zn. Among these elements, Fe and Zn are related with Parkinson and Alzheimer diseases, respectively. By the elemental maps, we can observe that the distribution of zinc was more pronounced in the hippocampus area, the distribution of iron was more conspicuous in the cortical region and bellows the thalamus and, moreover potassium and chlorine distributions were more present in the cortical area. Although, the small statistic, we can view that almost all measured elements are present in lower intensity in brains of rats with 3 weeks, and are usually the same for the other ages studied. (author)

  17. Hyperglycemia induces protein nonenzymeatic glycosylation in brain neurons of diabetic rats at early stage

    Institute of Scientific and Technical Information of China (English)

    Jingsheng Hu; Xueyi Ma; Shuli Sheng

    2007-01-01

    BACKGROUND: Protein nonenzymatic glycosylation is supposed to be one of mechanisms for chronic complications development in diabetes mellitus, and therefore, might play an important role in the neuronal degeneration.OBJECTIVE: To study the protein nonenzymatic glycosylation in brain neurons of diabetic rats, and to analyze the pathway of neuronal degeneration at the early stage of hyperglymecia.DESIGN: Randomized controlled animal experiment.SETTING: Department of Endocrinology, First hospital Affiliated to General Hospital of Chinese PLA and Beijing Laboratory for Brain Aging, Xuanwu Hospital Affiliated to Capital Medical University.MATERIALS: Thirty-five male Wistar rats (grade Ⅱ), aged 3 months old, and 11 male purebred Kunming mice (grade Ⅲ) without special pathogen, aged 3 months old, were provided by the Animal Room of Capital Medical University.METHODS: This experiment was carried out in the Beijing Laboratory for Brain Aging, Xuanwu Hospital Affiliated to Capital Medical University in 1998. The rats in the diabetic model group were intraperitoneally injected into 10 g/L STZ according to 60 mg/kg to establish rat models of diabetes mellitus. The blood glucose and body mass of rats in each group were determined respectively at 1, 2 and 3 months after modeling. The antibodies of advanced glycosylation end products (AGEs) of bovine serum albumin (anti-BSA) were self-prepared: ①The antigen of AGEs-BSA was prepared.②Eleven male Kuming mice (grade Ⅱ) of 3 months old without special pathogen were selected to inoculate AGEs-BSA. ③ The animals were immunized. ④Primary purification and detection of poly-antibodies of AGEs: the AGEs were performed immunohistochemical examination at 1 month after diabetic modeling by ELISA method.MAIN OUTCOME MEASURES: ① Detection results of blood glucose and body mass of rats in two groups at different time points. ② Determination of polyclonal antibody titer of AGEs-BSA. ③ Changes in immunohistochemical image of

  18. Hyperglycemia induces protein nonenzymeatic glycosylation in brain neurons of diabetic rats at early stage

    Institute of Scientific and Technical Information of China (English)

    Jingsheng Hu; Xueyi Ma; Shuli Sheng

    2007-01-01

    BACKGROUND: Protein nonenzymatic glycosylation is supposed to be one of mechanisms for chronic complications development in diabetes mellitus, and therefore, might play an important role in the neuronal degeneration.OBJECTIVE: To study the protein nonenzymatic glycosylation in brain neurons of diabetic rats, and to analyze the pathway of neuronal degeneration at the early stage of hyperglymecia.DESIGN: Randomized controlled animal experiment.SETTING: Department of Endocrinology, First hospital Affiliated to General Hospital of Chinese PLA and Beijing Laboratory for Brain Aging, Xuanwu Hospital Affiliated to Capital Medical University.MATERIALS: Thirty-five male Wistar rats (grade Ⅱ), aged 3 months old, and 11 male purebred Kunming mice (grade Ⅲ) without special pathogen, aged 3 months old, were provided by the Animal Room of Capital Medical University.METHODS: This experiment was carried out in the Beijing Laboratory for Brain Aging, Xuanwu Hospital Affiliated to Capital Medical University in 1998. The rats in the diabetic model group were intraperitoneally injected into 10 g/L STZ according to 60 mg/kg to establish rat models of diabetes mellitus. The blood glucose and body mass of rats in each group were determined respectively at 1, 2 and 3 months after modeling. The antibodies of advanced glycosylation end products (AGEs) of bovine serum albumin (anti-BSA) were self-prepared: ①The antigen of AGEs-BSA was prepared.②Eleven male Kuming mice (grade Ⅱ) of 3 months old without special pathogen were selected to inoculate AGEs-BSA. ③ The animals were immunized. ④Primary purification and detection of poly-antibodies of AGEs: the AGEs were performed immunohistochemical examination at 1 month after diabetic modeling by ELISA method.MAIN OUTCOME MEASURES: ① Detection results of blood glucose and body mass of rats in two groups at different time points. ② Determination of polyclonal antibody titer of AGEs-BSA. ③ Changes in immunohistochemical image of

  19. Indestructible plastic: the neuroscience of the new aging brain.

    Science.gov (United States)

    Holman, Constance; de Villers-Sidani, Etienne

    2014-01-01

    In recent years, research on experience-dependent plasticity has provided valuable insight on adaptation to environmental input across the lifespan, and advances in understanding the minute cellular changes underlying the brain's capacity for self-reorganization have opened exciting new possibilities for treating illness and injury. Ongoing work in this line of inquiry has also come to deeply influence another field: cognitive neuroscience of the normal aging. This complex process, once considered inevitable or beyond the reach of treatment, has been transformed into an arena of intense investigation and strategic intervention. However, important questions remain about this characterization of the aging brain, and the assumptions it makes about the social, cultural, and biological space occupied by cognition in the older individual and body. The following paper will provide a critical examination of the move from basic experiments on the neurophysiology of experience-dependent plasticity to the growing market for (and public conception of) cognitive aging as a medicalized space for intervention by neuroscience-backed technologies. Entangled with changing concepts of normality, pathology, and self-preservation, we will argue that this new understanding, led by personalized cognitive training strategies, is approaching a point where interdisciplinary research is crucial to provide a holistic and nuanced understanding of the aging process. This new outlook will allow us to move forward in a space where our knowledge, like our new conception of the brain, is never static. PMID:24782746

  20. NSAIDs may protect against age-related brain atrophy

    Directory of Open Access Journals (Sweden)

    Barbara B Bendlin

    2010-09-01

    Full Text Available The use of non-steroidal anti-inflammatory drugs (NSAIDs in humans is associated with brain differences including decreased number of activated microglia. In animals, NSAIDs are associated with reduced microglia, decreased amyloid burden, and neuronal preservation. Several studies suggest NSAIDs protect brain regions affected in the earliest stages of AD, including hippocampal and parahippocampal regions. In this cross-sectional study, we examined the protective effect of NSAID use on gray matter volume in a group of middle-aged and older NSAID users (n = 25 compared to non-user controls (n = 50. All participants underwent neuropsychological testing and T1-weighted magnetic resonance imaging. Non-user controls showed smaller volume in portions of the left hippocampus compared to NSAID users. Age-related loss of volume differed between groups, with controls showing greater medial temporal lobe volume loss with age compared to NSAID users. These results should be considered preliminary, but support previous reports that NSAIDs may modulate age-related loss of brain volume.

  1. Maternal age, reproduction and chromosomal aberrations in Wistar derived rats.

    Science.gov (United States)

    Niggeschulze, A; Kast, A

    1994-01-01

    The fertility of rats ranges from one to 18 months. In standard teratogenicity testing young, mature females are used which may not reflect the situation in women above 35 years old. Reproduction among different age groups of Wistar ats (strain Chbb: THOM) was compared at 3, 6, 9, 12, 15 and 18 months. At least 20 virgin females were inseminated per age group. The copulation rate did not differ between the groups. From the maternal age of 12 months, the pregnancy rate was significantly decreased, from the age of 9 months, the litter values were significantly lowered and the resorption rates were increased. Maternal age did not influence the incidence of fetal variations and malformations. Additionally, the chromosomal aberration rate in the bone marrow was evaluated in male and female rats. Twelve animals of each sex were scheduled per group, and studied at the age of 1, 3, 6, 12, 15, 18, 21 or 24 months. In males, the aberration rate increased continuously from 0.18 through 3%, while in females the increase continued from 0.33 to 2.29% at 15 months old when a plateau was reached. When testing new compounds for embryotoxicity or genotoxicity in female rats, the animals should be of comparable age to man in order to avoid a misinterpretation of spontaneous abnormalities. From these studies, however, it was concluded that the use of higher age groups of female rats in teratogenicity studies would not improve the risk assessment.

  2. Gastrodin protects neonatal rat brain against hypoxic-ischemic encephalopathy Acute therapeutic drug effects

    Institute of Scientific and Technical Information of China (English)

    Yanjun Niu; Zhengyong Jin

    2008-01-01

    BACKGROUND:Pharmacological experiments have demonstrated that gastrodin has a protective effect on neonatal rat brain subjected to hypoxia-ischemia; however,the underlying mechanism has not been fully elucidated. OBJECTIVE:The aim of this study was to investigate the acute therapeutic effects of gastrodin by observing prostaglandin B2 and 6-keto-prostaglandin F 1 a in brain issue of neonatal rats that received gastrodin injections immediately after hypoxia-ischemia.DESIGN:Single-factor design.SETTING:Department of Pediatrics,Affiliated Hospital of Yanbian University. MATERIALS:This study was performed in the Laboratory of the Department of Pediatrics,Affiliated Hospital of Yanbian University(key laboratory of provincial Health Department)from April to December 2003.Fifty-five Wistar rats of either gender,aged 7 days,were provided by the Laboratory Animal Center of Affiliated Hospital of Yanbian University.The rats were randomly divided into normal control(n=10), model(n=15),gastrodin-treated(n=15),and Danshen-treated(n=15)groups.The protocol was performed in accordance with guidelines from the Institute of Health Sciences for the use and care of animals.The following reagents were.used:Gastrodin(Sancai Medicine Group Co.,Ltd.,Zhongshan,Guangdong Province,China;component:gastrodin),Danshen(Conba Stock Company,Jinhua,Zhengjiang Province,China; component:salvia miltiorrhiza),and reagent kits for 125I-prostaglandin B2 and 125I-6-prostaglandin F 1 a (Research and Development Center for Science and Technology,General Hospital of Chinese PLA). METHODS:Rats in the normal control group received no treatment.Rats in the remaining 3 groups were anesthetized,followed by ligation of the left common carotid artery.One hour later,the rats were placed in a closed hypoxic box and allowed to inhale 8% oxygen-air(2.0-3.0 L/min)for 2 hours to develop hypoxic-ischemic encephalopathy.Immediately after lesion,rats in the gastrodin and Danshen-treated groups were intraperitoneally

  3. Blood-brain barrier permeability in rats exposed to electromagnetic fields used in wireless communication

    OpenAIRE

    Persson, Bertil R.; Leif G Salford; Brun, Arne

    1997-01-01

    iological effects of radio frequency electromagnetic fields (EMF) on the blood-brain barrier (BBB) have been studied in Fischer 344 rats of both sexes. The rats were not anaesthetised during the exposure. All animals were sacrificed by perfusion–fixation of the brains under chloralhydrate anaesthesia after the exposure. The brains were perfused with saline for 3–4 minutes, and thereafter perfusion fixed with 4% formaldehyde for 5–6 minutes. Whole coronal sections of the brains were d...

  4. Characteristics of muscarinic acetylcholine receptors in rat brain.

    Directory of Open Access Journals (Sweden)

    Nukina,Itaru

    1983-06-01

    Full Text Available Characteristics of muscarinic acetylcholine (ACh receptors were studied in the rat central nervous system (CNS using 3H-quinuclidinyl benzilate (QNB, an antagonist of muscarinic ACh receptors. Scatchard analysis indicated that the rat CNS had a single 3H-QNB binding site with an apparent dissociation constant (Kd of 5.0 X 10(-10 M. Li+, Zn++ and Cu++ had strong effects on 3H-QNB binding which indicates that these metal ions might play important roles at muscarinic ACh receptor sites in the brain. Since antidepressants and antischizophrenic drugs displaced the binding of 3H-QNB, the anticholinergic effects of these drugs need to be taken into account when they are applied clinically. The muscarinic ACh receptor was successfully solubilized with lysophosphatidylcholine. By gel chromatography, with a Sepharose 6B column, the solubilized muscarinic ACh receptor molecule eluted at the fraction corresponding to a Stokes' radius of 6.1 nm. With the use of sucrose-density-gradient centrifugation, the molecular weight of the solubilized muscarinic ACh receptor was determined to be about 90,000 daltons. The regional distribution of 3H-QNB binding in rat brain was examined, and the highest level of 3H-QNB binding was found to be in the striatum followed by cerebral cortex and hippocampus, indicating that muscarinic ACh mechanisms affect CNS function mainly through these areas.

  5. Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats.

    Science.gov (United States)

    Gu, Xiaohuan; Wei, Zheng Zachory; Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A; Yu, Shan Ping

    2015-05-01

    Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A 6-h hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15min or 2h after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood-brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201

  6. Localization of histidine decarboxylase mRNA in rat brain.

    Science.gov (United States)

    Bayliss, D A; Wang, Y M; Zahnow, C A; Joseph, D R; Millhorn, D E

    1990-08-01

    The recent cloning of a cDNA encoding fetal rat liver histidine decarboxylase (HDC), the synthesizing enzyme for histamine, allows the study of the central histaminergic system at the molecular level. To this end, Northern blot and in situ hybridization analyses were used to determine the regional and cellular distribution of neurons which express HDC mRNA in rat brain. Three hybridizing species which migrate as 1.6-, 2.6-, and 3.5-kb RNA were identified with Northern blots. The major (2.6 kb) and minor (3.5 kb) species, characteristic of HDC mRNA in fetal liver, were expressed at high levels in diencephalon and at just detectable levels in hippocampus, but not in other brain regions. In contrast, the 1.6-kb species was present in all brain regions examined except the olfactory bulb. Cells which contain HDC mRNA were found by in situ hybridization in the hypothalamus; HDC mRNA-containing cells were not detected in other areas, including the hippocampus. Hypothalamic neurons which express HDC mRNA were localized to all aspects of the tuberomammillary nucleus, a result consistent with previous immunohistochemical findings. PMID:19912749

  7. Male brain ages faster: the age and gender dependence of subcortical volumes.

    Science.gov (United States)

    Király, András; Szabó, Nikoletta; Tóth, Eszter; Csete, Gergő; Faragó, Péter; Kocsis, Krisztián; Must, Anita; Vécsei, László; Kincses, Zsigmond Tamás

    2016-09-01

    Effects of gender on grey matter (GM) volume differences in subcortical structures of the human brain have consistently been reported. Recent research evidence suggests that both gender and brain size influences volume distribution in subcortical areas independently. The goal of this study was to determine the effects of the interplay between brain size, gender and age contributing to volume differences of subcortical GM in the human brain. High-resolution T1-weighted images were acquired from 53 healthy males and 50 age-matched healthy females. Total GM volume was determined using voxel-based morphometry. We used model-based subcortical segmentation analysis to measure the volume of subcortical nuclei. Main effects of gender, brain volume and aging on subcortical structures were examined using multivariate analysis of variance. No significant difference was found in total brain volume between the two genders after correcting for total intracranial volume. Our analysis revealed significantly larger hippocampus volume for females. Additionally, GM volumes of the caudate nucleus, putamen and thalamus displayed a significant age-related decrease in males as compared to females. In contrast to this only the thalamic volume loss proved significant for females. Strikingly, GM volume decreases faster in males than in females emphasizing the interplay between aging and gender on subcortical structures. These findings might have important implications for the interpretation of the effects of unalterable factors (i.e. gender and age) in cross-sectional structural MRI studies. Furthermore, the volume distribution and changes of subcortical structures have been consistently related to several neuropsychiatric disorders (e.g. Parkinson's disease, attention deficit hyperactivity disorder, etc.). Understanding these changes might yield further insight in the course and prognosis of these disorders. PMID:26572143

  8. Age-related changes in the brain antioxidant status: modulation by dietary supplementation of Decalepis hamiltonii and physical exercise.

    Science.gov (United States)

    Ravikiran, Tekupalli; Sowbhagya, Ramachandregowda; Anupama, Sindhghatta Kariyappa; Anand, Santosh; Bhagyalakshmi, Dundaiah

    2016-08-01

    The synergistic effects of physical exercise and diet have profound benefits on brain function. The present study was aimed to determine the effects of exercise and Decalepis hamiltonii (Dh) on age-related responses on the antioxidant status in discrete regions of rat brain. Male Wistar albino rats of 4 and 18 months old were orally supplemented with Dh extract and swim trained at 3 % intensity for 30 min/day, 5 days/week, for a period of 30 days. Supplementation of 100 mg Dh aqueous extract/kg body weight and its combination with exercise significantly elevated the antioxidant enzyme activities irrespective of age. Age-related and region-specific changes were observed in superoxide levels, and protein carbonyl and malondialdehyde contents, and were found to be decreased in both trained and supplemented groups. Levels of total thiols, protein, and nonprotein thiols decreased with age and significantly increased in the SW-T(+100 mg) groups. Our results demonstrated that the interactive effects of two treatments enhanced the antioxidant status and decreased the risk of protein and lipid oxidation in the rat brain. PMID:27379504

  9. Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

    Directory of Open Access Journals (Sweden)

    R.L. Figueira

    2016-01-01

    Full Text Available Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC. This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group: 1 preterm control (PTC, 2 preterm ventilated (PTV, 3 preterm asphyxiated (PTA, 4 preterm asphyxiated and ventilated (PTAV, 5 term control (TC, 6 term ventilated (TV, 7 term asphyxiated (TA, and 8 term asphyxiated and ventilated (TAV. We measured body, brain, and intestine weights and respective ratios [(BW, (BrW, (IW, (BrW/BW and (IW/BW]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus and intestine (jejunum/ileum tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP. IW was lower in the TA than in the other terms (P<0.05, and the IW/BW ratio was lower in the TA than in the TAV (P<0.005. PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex and TA (cortex/hippocampus (P<0.005. I-FABP was higher in PTAV (P<0.005 and TA (ileum (P<0.05. I-FABP expression was increased in PTAV subgroup (P<0.0001. Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers.

  10. The blood-brain barrier penetration and distribution of PEGylated fluorescein-doped magnetic silica nanoparticles in rat brain

    International Nuclear Information System (INIS)

    PEGylated PAMAM conjugated fluorescein-doped magnetic silica nanoparticles (PEGylated PFMSNs) have been synthesized for evaluating their ability across the blood-brain barrier (BBB) and distribution in rat brain. The obtained nanoparticles were characterized by transmission electron microscopy (TEM), thermal gravimetry analyses (TGA), zeta potential (ζ-potential) titration, and X-ray photoelectron spectroscopy (XPS). The BBB penetration and distribution of PEGylated PFMSNs and FMSNs in rat brain were investigated not only at the cellular level with Confocal laser scanning microscopy (CLSM), but also at the subcellular level with transmission electron microscopy (TEM). The results provide direct evidents that PEGylated PFMSNs could penetrate the BBB and spread into the brain parenchyma.

  11. Neural Plastic Effects of Cognitive Training on Aging Brain

    OpenAIRE

    Leung, Natalie T. Y.; Tam, Helena M. K.; Leung W. Chu; Kwok, Timothy C. Y.; Felix Chan; Lam, Linda C. W.; Jean Woo; Lee, Tatia M. C.

    2015-01-01

    Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cogni...

  12. NREM sleep oscillations and brain plasticity in aging

    OpenAIRE

    Stuart eFogel; Nicolas eMartin; Marjolaine eLafortune; Marc eBarakat; Karen eDebas; Samuel eLaventure; Véronique eLatreille; Jean-François eGagnon; Julien eDoyon; Julie eCarrier

    2012-01-01

    The human electroencephalogram (EEG) during non-rapid eye movement sleep (NREM) is characterized mainly by high-amplitude (> 75 µV), slow-frequency (< 4 Hz) waves (slow waves; SW) and sleep spindles (~11-15 Hz; > 0.25 s). These NREM oscillations play a crucial role in brain plasticity, and importantly, NREM sleep oscillations change considerably with aging. This review discusses the association between NREM sleep oscillations and cerebral plasticity as well as the functional imp...

  13. Cerebrolysin attenuates blood-brain barrier and brain pathology following whole body hyperthermia in the rat.

    Science.gov (United States)

    Sharma, Hari Shanker; Zimmermann-Meinzingen, Sibilla; Sharma, Aruna; Johanson, Conrad E

    2010-01-01

    The possibility that Cerebrolysin, a mixture of several neurotrophic factors, has some neuroprotective effects on whole body hyperthermia (WBH) induced breakdown of the blood-brain barrier (BBB), blood-CSF barrier (BCSFB), brain edema formation and neuropathology were examined in a rat model. Rats subjected to a 4 h heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator exhibited profound increases in BBB and BCSFB permeability to Evans blue and radioiodine tracers compared to controls. Hippocampus, caudate nucleus, thalamus and hypothalamus exhibited pronounced increase in water content and brain pathology following 4 h heat stress. Pretreatment with Cerebrolysin (1, 2 or 5 mL/kg i.v.) 24 h before WBH significantly attenuated breakdown of the BBB or BCSFB and brain edema formation. This effect was dose dependent. Interestingly, the cell and tissue injury following WBH in cerebrolysin-treated groups were also considerably reduced. These novel observations suggest that cerebrolysin can attenuate WBH induced BBB and BCSFB damage resulting in neuroprotection.

  14. Differential Proteomics in the Aging Noble Rat Ventral Prostate

    OpenAIRE

    Lam, Ying Wai; Tam, Neville N. C.; Evans, James E.; Green, Karin M.; Zhang, Xiang; Ho, Shuk-Mei

    2008-01-01

    Incidence of prostatic diseases increases dramatically with age which may be related to a decline in androgen support. However, the key mechanisms underlying prostate aging remain unclear. In the present study, we investigated the aging process in the ventral prostate of Noble rats by identifying differentially expressed prostate proteins between 3- and 16-month-old animals using ICAT and MS. In total, 472 proteins were identified with less than a 1% false positive rate, among which 34 were d...

  15. Lucid dreaming: an age-dependent brain dissociation.

    Science.gov (United States)

    Voss, Ursula; Frenzel, Clemens; Koppehele-Gossel, Judith; Hobson, Allan

    2012-12-01

    The current study focused on the distribution of lucid dreams in school children and young adults. The survey was conducted on a large sample of students aged 6-19 years. Questions distinguished between past and current experience with lucid dreams. Results suggest that lucid dreaming is quite pronounced in young children, its incidence rate drops at about age 16 years. Increased lucidity was found in those attending higher level compared with lower level schools. Taking methodological issues into account, we feel confident to propose a link between the natural occurrence of lucid dreaming and brain maturation.

  16. Increased self-diffusion of brain water in normal aging

    DEFF Research Database (Denmark)

    Gideon, P; Thomsen, C; Henriksen, O

    1994-01-01

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

  17. Lucid dreaming: an age-dependent brain dissociation.

    Science.gov (United States)

    Voss, Ursula; Frenzel, Clemens; Koppehele-Gossel, Judith; Hobson, Allan

    2012-12-01

    The current study focused on the distribution of lucid dreams in school children and young adults. The survey was conducted on a large sample of students aged 6-19 years. Questions distinguished between past and current experience with lucid dreams. Results suggest that lucid dreaming is quite pronounced in young children, its incidence rate drops at about age 16 years. Increased lucidity was found in those attending higher level compared with lower level schools. Taking methodological issues into account, we feel confident to propose a link between the natural occurrence of lucid dreaming and brain maturation. PMID:22639960

  18. Age-related hearing loss: ear and brain mechanisms.

    Science.gov (United States)

    Frisina, Robert D

    2009-07-01

    Loss of sensory function in the aged has serious consequences for economic productivity, quality of life, and healthcare costs in the billions each year. Understanding the neural and molecular bases will pave the way for biomedical interventions to prevent, slow, or reverse these conditions. This chapter summarizes new information regarding age changes in the auditory system involving both the ear (peripheral) and brain (central). A goal is to provide findings that have implications for understanding some common biological underpinnings that affect sensory systems, providing a basis for eventual interventions to improve overall sensory functioning, including the chemical senses.

  19. Brain Plasticity and Motor Practice in Cognitive Aging

    Directory of Open Access Journals (Sweden)

    Liuyang eCai

    2014-03-01

    Full Text Available For more than two decades, there have been extensive studies of experience-based neural plasticity exploring effective applications of brain plasticity for cognitive and motor development. Research suggests that human brains continuously undergo structural reorganization and functional changes in response to stimulations or training. From a developmental point of view, the assumption of lifespan brain plasticity has been extended to older adults in terms of the benefits of cognitive training and physical therapy. To summarize recent developments, first, we introduce the concept of neural plasticity from a developmental perspective. Secondly, we note that motor learning often refers to deliberate practice and the resulting performance enhancement and adaptability. We discuss the close interplay between neural plasticity, motor learning and cognitive aging. Thirdly, we review research on motor skill acquisition in older adults with, and without, impairments relative to aging-related cognitive decline. Finally, to enhance future research and application, we highlight the implications of neural plasticity in skills learning and cognitive rehabilitation for the aging population.

  20. Brain plasticity and motor practice in cognitive aging

    Science.gov (United States)

    Cai, Liuyang; Chan, John S. Y.; Yan, Jin H.; Peng, Kaiping

    2014-01-01

    For more than two decades, there have been extensive studies of experience-based neural plasticity exploring effective applications of brain plasticity for cognitive and motor development. Research suggests that human brains continuously undergo structural reorganization and functional changes in response to stimulations or training. From a developmental point of view, the assumption of lifespan brain plasticity has been extended to older adults in terms of the benefits of cognitive training and physical therapy. To summarize recent developments, first, we introduce the concept of neural plasticity from a developmental perspective. Secondly, we note that motor learning often refers to deliberate practice and the resulting performance enhancement and adaptability. We discuss the close interplay between neural plasticity, motor learning and cognitive aging. Thirdly, we review research on motor skill acquisition in older adults with, and without, impairments relative to aging-related cognitive decline. Finally, to enhance future research and application, we highlight the implications of neural plasticity in skills learning and cognitive rehabilitation for the aging population. PMID:24653695

  1. Detection of cocaine induced rat brain activation by photoacoustic tomography

    Science.gov (United States)

    Jo, Janggun; Yang, Xinmai

    2011-01-01

    Photoacoustic tomography (PAT) was used to detect the progressive changes on the cerebral cortex of Sprague Dawley rats after the administration of cocaine hydrochloride. Different concentrations (0, 2.5, and 5.0 mg per kg body) of cocaine hydrochloride in saline solution were injected into Sprague Dawley rats through tail veins. Cerebral cortex images of the animals were continuously acquired by PAT. For continuous observation, PAT system used multi-transducers to reduce the scanning time and maintain a good signal-to-noise ratio (SNR). The obtained photoacoustic images were compared with each other and confirmed that changes in blood volume were induced by cocaine hydrochloride injection. The results demonstrate that PAT may be used to detect the effects of drug abuse-induced brain activation. PMID:21163301

  2. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

    Directory of Open Access Journals (Sweden)

    Judith R Homberg

    Full Text Available The selective serotonin reuptake inhibitor (SSRI Prozac® (fluoxetine is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg at postnatal day (PND 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7-14 days after the last injection when (norfluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (norfluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT(1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential

  3. Age at developmental cortical injury differentially Alters corpus callosum volume in the rat

    Directory of Open Access Journals (Sweden)

    Rosen Glenn D

    2007-11-01

    Full Text Available Abstract Background Freezing lesions to developing rat cortex induced between postnatal day (P one and three (P1 – 3 lead to malformations similar to human microgyria, and further correspond to reductions in brain weight and cortical volume. In contrast, comparable lesions on P5 do not produce microgyric malformations, nor the changes in brain weight seen with microgyria. However, injury occurring at all three ages does lead to rapid auditory processing deficits as measured in the juvenile period. Interestingly, these deficits persist into adulthood only in the P1 lesion case 1. Given prior evidence that early focal cortical lesions induce abnormalities in cortical morphology and connectivity 1234, we hypothesized that the differential behavioral effects of focal cortical lesions on P1, P3 or P5 may be associated with underlying neuroanatomical changes that are sensitive to timing of injury. Clinical studies indicate that humans with perinatal brain injury often show regional reductions in corpus callosum size and abnormal symmetry, which frequently correspond to learning impairments 567. Therefore, in the current study the brains of P1, 3 or 5 lesion rats, previously evaluated for brain weight, and cortical volume changes and auditory processing impairments (P21-90, were further analyzed for changes in corpus callosum volume. Results Results showed a significant main effect of Treatment on corpus callosum volume [F (1,57 = 10.2, P Conclusion Decrements in corpus callosum volume in the P1 and 3 lesion groups are consistent with the reductions in brain weight and cortical volume previously reported for microgyric rats 18. Current results suggest that disruption to the cortical plate during early postnatal development may lead to more widely dispersed neurovolumetric anomalies and subsequent behavioral impairments 1, compared with injury that occurs later in development. Further, these results suggest that in a human clinical setting decreased

  4. The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability.

    Science.gov (United States)

    Blau, Christoph W; Cowley, Thelma R; O'Sullivan, Joan; Grehan, Belinda; Browne, Tara C; Kelly, Laura; Birch, Amy; Murphy, Niamh; Kelly, Aine M; Kerskens, Christian M; Lynch, Marina A

    2012-05-01

    In view of the increase in the aging population and the unavoidable parallel increase in the incidence of age-related neurodegenerative diseases, a key challenge in neuroscience is the identification of clinical signatures which change with age and impact on neuronal and cognitive function. Early diagnosis offers the possibility of early therapeutic intervention, thus magnetic resonance imaging (MRI) is potentially a powerful diagnostic tool. We evaluated age-related changes in relaxometry, blood flow, and blood-brain barrier (BBB) permeability in the rat by magnetic resonance imaging and assessed these changes in the context of the age-related decrease in synaptic plasticity. We report that T2 relaxation time was decreased with age; this was coupled with a decrease in gray matter perfusion, suggesting that the observed microglial activation, as identified by increased expression of CD11b, MHCII, and CD68 by immunohistochemistry, flow cytometry, or polymerase chain reaction (PCR), might be a downstream consequence of these changes. Increased permeability of the blood-brain barrier was observed in the perivascular area and the hippocampus of aged, compared with young, rats. Similarly there was an age-related increase in CD45-positive cells by flow cytometry, which are most likely infiltrating macrophages, with a parallel increase in the messenger mRNA expression of chemokines IP-10 and MCP-1. These combined changes may contribute to the deficit in long-term potentiation (LTP) in perforant path-granule cell synapses of aged animals.

  5. Elemental concentration analysis in the brain of young and old Wistar rats by total reflection X-ray fluorescence spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Serpa, Renata F.B.; Jesus, Edgar F.O. de; Lopes, Ricardo T. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE). Nuclear Instrumentation Lab.]. E-mail: renata@lin.ufrj.br; Anjos, Marcelino J. dos [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Physics Inst.]. E-mail: marcelin@lin.ufrj.br; Carmo, Maria G.T. do [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Nutrition Inst.; Rocha, Monica S. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Dept. of Basics and Clinic Pharmacy; Moreira, Silvana [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Civil Engineering Dept.; Martinez, Ana M.B. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Dept. of Histology and Embryology

    2007-07-01

    It is well known that aging is associated with neurobehavioral deficits. The aging process of human brain is characterized by progressive neuronal loss. Furthermore, certain brain areas are more vulnerable to neuronal degeneration than others, reflecting an altered resistance to stress of the tissue itself and/or the lack of adequate immunological defense mechanisms in these regions. About the elemental levels in the brain, it is known that the excess ou deficiency of some elements are toxic for human healthy, being also related to several neurodegenerative diseases. In this way, the main goal of this work was to determine the elemental concentration in the hippocampus of young and old male (n = 10) and female (n = 10) Wistar rats by total reflection X-ray fluorescence spectrometry with synchrotron radiation (SR-TXRF). These measurements were carried out at XRF beam line at Light Synchrotron Brazilian Laboratory, Campinas, Brazil. About the results, we could observe that Al, Fe, Cu, Zn and Br levels were higher in the hippocampus of the old female rats than the young ones. On the other hand, only Cu levels were higher in the hippocampus of the old male rats than the young ones. Therefore, the aging of the hippocampus of the female rats can be characterized by an accumulate for Al, Fe, Cu, Zn and Br. The excess in these elements levels are also associated with several neurodegenerative disorders, such as Alzheimer' disease, Parkinson's disease and Huntington's disease. (author)

  6. Auditory event-related brain potentials for an early discrimination between normal and pathological brain aging

    Institute of Scientific and Technical Information of China (English)

    Juliana Dushanova; Mario Christov

    2013-01-01

    The brain as a system with gradually decreasing resources maximizes its chances by reorganizing neural networks to ensure efficient performance. Auditory event-related potentials were recorded in 28 healthy volunteers comprising 14 young and 14 elderly subjects in auditory discrimination motor task (low frequency tone – right hand movement and high frequency tone – left hand movement). The amplitudes of the sensory event-related potential components (N1, P2) were more pronounced with increasing age for either tone and this effect for P2 amplitude was more pronounced in the frontal region. The latency relationship of N1 between the groups was tone-dependent, while that of P2 was tone-independent with a prominent delay in the elderly group over all brain regions. The amplitudes of the cognitive components (N2, P3) diminished with increasing age and the hemispheric asymmetry of N2 (but not for P3) reduced with increasing age. Prolonged N2 latency with increasing age was widespread for either tone while between-group difference in P3 latency was tone-dependent. High frequency tone stimulation and movement requirements lead to P3 delay in the elderly group. The amplitude difference of the sensory components between the age groups could be due to a general greater alertness, less expressed habituation, or decline in the ability to retreat attentional resources from the stimuli in the elderly group. With aging, a neural circuit reorganization of the brain activity affects the cognitive processes. The approach used in this study is useful for an early discrimination between normal and pathological brain aging for early treatment of cognitive alterations and dementia.

  7. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    Science.gov (United States)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  8. Non-invasive brain stimulation of the aging brain: State of the art and future perspectives.

    Science.gov (United States)

    Tatti, Elisa; Rossi, Simone; Innocenti, Iglis; Rossi, Alessandro; Santarnecchi, Emiliano

    2016-08-01

    Favored by increased life expectancy and reduced birth rate, worldwide demography is rapidly shifting to older ages. The golden age of aging is not only an achievement but also a big challenge because of the load of the elderly on social and medical health care systems. Moreover, the impact of age-related decline of attention, memory, reasoning and executive functions on self-sufficiency emphasizes the need of interventions to maintain cognitive abilities at a useful degree in old age. Recently, neuroscientific research explored the chance to apply Non-Invasive Brain Stimulation (NiBS) techniques (as transcranial electrical and magnetic stimulation) to healthy aging population to preserve or enhance physiologically-declining cognitive functions. The present review will update and address the current state of the art on NiBS in healthy aging. Feasibility of NiBS techniques will be discussed in light of recent neuroimaging (either structural or functional) and neurophysiological models proposed to explain neural substrates of the physiologically aging brain. Further, the chance to design multidisciplinary interventions to maximize the efficacy of NiBS techniques will be introduced as a necessary future direction. PMID:27221544

  9. Risperidone treatment increases CB1 receptor binding in rat brain

    DEFF Research Database (Denmark)

    Secher, Anna; Husum, Henriette; Holst, Birgitte;

    2010-01-01

    BACKGROUND/AIMS: Body weight gain is a common side effect of treatment with antipsychotics, but the mechanisms underlying this weight gain are unknown. Several factors may be involved in antipsychotic-induced body weight gain including the cannabinoid receptor 1 (CB(1)), the serotonin receptor 2C...... positively correlated with visceral fat mass. Risperidone treatment increased CB(1) receptor binding in the arcuate nucleus (40%), hippocampus (25-30%) and amygdala (35%) without concurrent alterations in the CB(1) receptor mRNA. Risperidone treatment increased adiponectin mRNA. CONCLUSION: The present study...... showed that risperidone treatment altered CB(1) receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB(1) receptor density in brain regions involved in appetite and regulation of metabolic function....

  10. Brain plasticity of rats exposed to prenatal immobilization stress

    Directory of Open Access Journals (Sweden)

    Badalyan B. Yu.

    2011-10-01

    Full Text Available Aim. This histochemical and immunohistochemical study was aimed at examining the brain cellular structures of newborn rats exposed to prenatal immobilization (IMO stress. Methods. Histochemical method on detection of Ca2+-dependent acid phosphatase activity and ABC immunohistochemical technique. Results. Cell structures with radial astrocytes marker GFAP, neuroepithelial stem cell marker gene nestin, stem-cells marker and the hypothalamic neuroprotective proline-rich polypeptide PRP-1 (Galarmin, a natural cytokine of a common precursor to neurophysin vasopressin associated glycoprotein have been revealed in several brain regions. Conclusions. Our findings indicate the process of generation of new neurons in response to IMO and PRP-1 involvement in this recovery mechanism, as PRP-1-Ir was detected in the above mentioned cell structures, as well as in the neurons and nerve fibers.

  11. Transient and persistent expression of NT-3/HDNF mRNA in the rat brain during postnatal development.

    Science.gov (United States)

    Friedman, W J; Ernfors, P; Persson, H

    1991-06-01

    Neurotrophin-3 (NT-3) is closely related to two known neurotrophic agents, NGF and brain-derived neurotrophic factor (BDNF), and acts upon overlapping, yet distinct, populations of peripheral ganglia. NT-3 mRNA expression in the adult rat brain is largely confined to the hippocampus. In this study, we have used in situ hybridization to examine expression of this novel neurotrophic factor during postnatal development. The striking observation was made that NT-3 mRNA was transiently expressed at high levels in the cingulate cortex during the first 2 weeks of age. In the hippocampus, the adult pattern of expression, in the CA2, medial CA1, and granule layer of the dentate gyrus, was detected at all ages examined. However, there were two major differences in NT-3 mRNA expression in the developing hippocampus: Labeled cells were detected in the hilar region of the dentate gyrus at postnatal day 1 (P1) and 1 week that were absent by 2 weeks of age. Further, the caudal hippocampus, which has a lower intensity of labeling than the rostral region in the adult, was devoid of NT-3-expressing cells in the P1 and 1-week-old rat brain. These data indicate a substantial plasticity in NT-3 mRNA expression and suggest that the spectrum of neurons supported by NT-3 during development is partially different from that in the mature rat brain. PMID:2045877

  12. Type 3 Adenylyl Cyclase and Somatostatin Receptor 3 Expression Persists in Aged Rat Neocortical and Hippocampal Neuronal Cilia

    Science.gov (United States)

    Guadiana, Sarah M.; Parker, Alexander K.; Filho, Gileno F.; Sequeira, Ashton; Semple-Rowland, Susan; Shaw, Gerry; Mandel, Ronald J.; Foster, Thomas C.; Kumar, Ashok; Sarkisian, Matthew R.

    2016-01-01

    The primary cilia of forebrain neurons assemble around birth and become enriched with neuromodulatory receptors. Our understanding of the permanence of these structures and their associated signaling pathways in the aging brain is poor, but they are worthy of investigation because disruptions in neuronal cilia signaling have been implicated in changes in learning and memory, depression-like symptoms, and sleep anomalies. Here, we asked whether neurons in aged forebrain retain primary cilia and whether the staining characteristics of aged cilia for type 3 adenylyl cyclase (ACIII), somatostatin receptor 3 (SSTR3), and pericentrin resemble those of cilia in younger forebrain. To test this, we analyzed immunostained sections of forebrain tissues taken from young and aged male Fischer 344 (F344) and F344 × Brown Norway (F344 × BN) rats. Analyses of ACIII and SSTR3 in young and aged cortices of both strains of rats revealed that the staining patterns in the neocortex and hippocampus were comparable. Virtually every NeuN positive cell examined possessed an ACIII positive cilium. The lengths of ACIII positive cilia in neocortex were similar between young and aged for both strains, whereas in F344 × BN hippocampus, the cilia lengths increased with age in CA1 and CA3, but not in dentate gyrus (DG). Additionally, the percentages of ACIII positive cilia that were also SSTR3 positive did not differ between young and aged tissues in either strain. We also found that pericentrin, a protein that localizes to the basal bodies of neuronal cilia and functions in primary cilia assembly, persisted in aged cortical neurons of both rat strains. Collectively, our data show that neurons in aged rat forebrain possess primary cilia and that these cilia, like those present in younger brain, continue to localize ACIII, SSTR3, and pericentrin. Further studies will be required to determine if the function and signaling pathways regulated by cilia are similar in aged compared to young brain

  13. Data for mitochondrial proteomic alterations in the developing rat brain.

    Science.gov (United States)

    Villeneuve, Lance M; Stauch, Kelly L; Fox, Howard S

    2014-12-01

    Mitochondria are a critical organelle involved in many cellular processes, and due to the nature of the brain, neuronal cells are almost completely reliant on these organelles for energy generation. Due to the fact that biomedical research tends to investigate disease state pathogenesis, one area of mitochondrial research commonly overlooked is homeostatic responses to energy demands. Therefore, to elucidate mitochondrial alterations occurring during the developmentally important phase of E18 to P7 in the brain, we quantified the proteins in the mitochondrial proteome as well as proteins interacting with the mitochondria. We identified a large number of significantly altered proteins involved in a variety of pathways including glycolysis, mitochondrial trafficking, mitophagy, and the unfolded protein response. These results are important because we identified alterations thought to be homeostatic in nature occurring within mitochondria, and these results may be used to identify any abnormal deviations in the mitochondrial proteome occurring during this period of brain development. A more comprehensive analysis of this data may be obtained from the article "Proteomic analysis of mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands" in the Journal of Proteomics. PMID:26217684

  14. Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain

    Science.gov (United States)

    Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

    1998-12-01

    Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

  15. 不同类型音乐对老年大鼠脑组织海马区神经细胞凋亡的影响%Effects of different types of music on neuronal apoptosis of hippocampus of brain tissue of aged rats

    Institute of Scientific and Technical Information of China (English)

    何颖; 李淑梅; 马洪喜

    2014-01-01

    目的:探讨不同类型音乐对老年大鼠脑组织海马区Caspase-3和Livin表达水平的影响。方法:取健康老年雄性Wistar大鼠40只,随机分为:空白对照组、莫扎特音乐组、梁祝音乐组和摇滚音乐组,每组各10只;每天上午水迷宫训练同时音乐干预2 h,下午单纯音乐干预2 h,连续7天,第8天处死大鼠取血液及脑组织,采用ELISA检测大鼠血清及脑组织中Caspase-3和Livin蛋白含量的变化水平;采用免疫组织化学法检测大鼠脑组织海马区中Caspase-3和Livin蛋白表达水平;采用实时-PCR检测大鼠脑组织中Caspase-3和Livin的基因变化水平。结果:与对照组比较,莫扎特音乐组、梁祝音乐组大鼠血清及脑组织中Caspase-3蛋白含量、蛋白表达和基因水平均降低有统计学意义(P<0.01),Livin蛋白含量、蛋白表达和基因水平均升高有统计学意义(P<0.01),莫扎特音乐组略好于梁祝音乐组差异无统计学意义(P>0.05);而摇滚音乐组大鼠血清及脑组织中Caspase-3和Livin蛋白含量、蛋白表达和基因水平均无差异无统计学意义( P>0.05)。结论:莫扎特音乐组和梁祝音乐组能通过降低血清及脑组织中Caspase-3水平、提高Livin水平,抑制机体脑神经细胞的凋亡,从而起到神经保护作用;而摇滚音乐组在本研究中效果不明显。%Objective:To explore the effects of different types of music on Caspase-3 and Livin expression levels of the hippocampus of brain tissue of aged rats.Methods: Healthly elderly male Wistar rats 40 were randomly divided into :control group , Mozart music group ,Liangzhu music group and rock music group ,n=10;water maze training every morning while music intervention 2 h,afternoon pure music intervention 2 h,continuous 7 d,the eighth days ,the rats were sacrificed and taking blood and brain tissue ,by ELISA in serum and brain tissue Caspase-3 and Livin protein

  16. Uptake of [14C]deoxyglucose into brain of young rats with inherited hydrocephalus

    International Nuclear Information System (INIS)

    The effect of hydrocephalus on cerebral glucose utilization as reflected by deoxyglucose uptake has been examined in rats with inherited hydrocephalus at 10, 20, and 28 days after birth using a semiquantitative method. Injection of [14C]deoxyglucose intraperitoneally was followed by freezing the brain, sectioning, and quantitative autoradiography of 10 brain regions. Brain [14C] concentration, cortical thickness, and plasma glucose concentrations were measured. Maximal thinning of the cerebral cortex had already occurred by 10 days after birth, although obvious symptoms such as gait disturbance developed after 20 days. In control rats, the cerebral isotope concentration was lower and more homogeneous at 10 days than at 20 or 28 days, which may be a reflection of the use of metabolic substrates other than glucose in younger animals. In order to make comparisons between control and hydrocephalic groups, tissue isotope concentrations were normalized to cerebellar cortex which was not affected by the hydrocephalus at any age. In hydrocephalic rats at 10 and 20 days, the concentration of [14C] was lower in all areas except the inferior colliculi and pons but the reduction was only significant in the sensory-motor cortex at 10 days and in the caudate nuclei at 20 days. By 28 days after birth, all areas except the cerebellum (six cortical regions, inferior colliculi, pons, and caudate) had significantly lower isotope concentrations in the hydrocephalic group. It is concluded that cerebral glucose metabolism is significantly reduced by 28 days after birth in H-Tx rats with congenital hydrocephalus and that less marked reductions occur prior to 28 days

  17. [DYNAMICS OF GLUTAMINE SYNTHASE ACTIVITY IN RAT BRAIN IN PRENATAL HYPOXIA MODEL].

    Science.gov (United States)

    Khairova, V R; Safarov, M I

    2015-01-01

    Prenatal ontogenesis is a period of high sensitivity to stressful impact, so any stressor can lead to changes of physiological, biochemical indicators, behavioral and cognitive functions. The most common and clinically significant stress factor, which the embryo may be exposed during embryonic development, is hypoxia. In this case pathological changes in the central nervous system depend on the duration and severity of hypoxic exposure, individual tolerance and the stage of prenatal development, at each of which in the brain take place the basic histogenetic processes. By activating energetically disadvantageous anaerobic glycolysis hypoxia leads to excess of glutamate emission and cell apoptosis. Glutamine synthase is a basic enzyme that regulates metabolism of glutamate, catalyzing conversion of glutamate to glutamine with ammonia detoxification. The aim of the presented work was to reveal changes in the activity of one of the key enzyme of glutamate metabolism- glutamine synthetase in the brain of offspring of white rats undergone to hypoxia at different stages of prenatal ontogenesis. Hypoxia was created by placing female rats at stages of the pregnancy, corresponding to progestation period of organogenesis and fetal period of prenatal development, in the hypobaric chamber with exposure to 5% oxygen and 95% nitrogen gas mixture during 30 minutes per day. The offspring obtained from females of control and experimental groups were used for biochemical determinations in the age of 1 and 3 month. It has been established that hypoxia exposed to pregnant females during embryonic organogenesis causes significant changes in enzyme activity, particularly pronounced in the cerebral cortex and cerebellum, as compared with progestational and fetal hypoxia. Enzyme activity decreased in a greater degree in one-month-old rats undergone to prenatal hypoxia, than three- month-old animals. Thus, stress during intensive processes of proliferation and migration of cells of the

  18. Indestructible plastic: The neuroscience of the new aging brain

    Directory of Open Access Journals (Sweden)

    Constance eHolman

    2014-04-01

    Full Text Available In recent years, research on experience-dependent plasticity has provided valuable insight on adaptation to environmental input across the lifespan, and advances in understanding the minute cellular changes underlying the brain’s capacity for self-reorganization have opened exciting new possibilities for treating illness and injury. Ongoing work in this line of inquiry has also come to deeply influence another field: the cognitive neuroscience of the normal aging. This complex process, once dubbed as inevitable or beyond the reach of treatment, has been transformed into an arena of intense investigation and strategic intervention. However, important questions remain about this characterization of the aging brain, and the assumptions it makes about the social, cultural, and biological space occupied by cognition in the older individual and body. The following paper will provide a critical examination of the move from basic experiments on the neurophysiology of experience-dependent plasticity to the growing market for (and public conception of cognitive aging as a medicalized space for intervention by neuroscience-backed technologies. Entangled with changing concepts of normality, pathology, and self-preservation, we will argue that this new understanding, led by personalized cognitive training strategies, is approaching a point where interdisciplinary research is crucial to provide a holistic and nuanced understanding of the aging process. This new outlook will allow us to move forward in a space where our knowledge, like our new conception of the brain, is never static.

  19. Role of stanniocalcin1 in brain injury of coal-burning-borne fluorosis rats

    Institute of Scientific and Technical Information of China (English)

    陈旭义

    2013-01-01

    Objective To observe the change of stanniocalcin 1(STC1) and calcium content in brain of coal-burning-borne fluorosis rats,and to explore the role of STC1 in brain injury of coal-burning-borne fluorosis.Methods Twenty four male SD rats were randomly divided into control,low,medium,

  20. Distribution of the mRNA for protein phosphatase T in rat brain

    NARCIS (Netherlands)

    Becker, W; Buttini, M; Limonta, S; Boddeke, H; Joost, HG

    1996-01-01

    We have recently cloned a novel protein serine/threonine phosphatase (PPT) from rat mRNA which is predominantly expressed in the brain (Becker et al., J. Biol. Chem., 269 (1994) 22586-22592). In the present study, the regional distribution of PPT mRNA in the brain of adult rats was characterized by

  1. Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

    Science.gov (United States)

    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2010-02-01

    Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

  2. Cross-activation and detraining effects of tongue exercise in aged rats.

    Science.gov (United States)

    Schaser, Allison J; Ciucci, Michelle R; Connor, Nadine P

    2016-01-15

    Voice and swallowing deficits can occur with aging. Tongue exercise paired with a swallow may be used to treat swallowing disorders, but may also benefit vocal function due to cross-system activation effects. It is unknown how exercise-based neuroplasticity contributes to behavior and maintenance following treatment. Eighty rats were used to examine behavioral parameters and changes in neurotrophins after tongue exercise paired with a swallow. Tongue forces and ultrasonic vocalizations were recorded before and after training/detraining in young and old rats. Tissue was analyzed for neurotrophin content. Results showed tongue exercise paired with a swallow was associated with increased tongue forces at all ages. Gains diminished after detraining in old rats. Age-related changes in vocalizations, neurotrophin 4 (NT4), and brain derived neurotrophic factor (BDNF) were found. Minimal cross-system activation effects were observed. Neuroplastic benefits were demonstrated with exercise in old rats through behavioral improvements and up-regulation of BDNF in the hypoglossal nucleus. Tongue exercise paired with a swallow should be developed, studied, and optimized in human clinical research to treat swallowing and voice disorders in elderly people.

  3. Alterations in brain neurotrophic and glial factors following early age chronic methylphenidate and cocaine administration.

    Science.gov (United States)

    Simchon-Tenenbaum, Yaarit; Weizman, Abraham; Rehavi, Moshe

    2015-04-01

    Attention deficit hyperactivity disorder (ADHD) overdiagnosis and a pharmacological attempt to increase cognitive performance, are the major causes for the frequent (ab)use of psychostimulants in non-ADHD individuals. Methylphenidate is a non-addictive psychostimulant, although its mode of action resembles that of cocaine, a well-known addictive and abused drug. Neuronal- and glial-derived growth factors play a major role in the development, maintenance and survival of neurons in the central nervous system. We hypothesized that methylphenidate and cocaine treatment affect the expression of such growth factors. Beginning on postnatal day (PND) 14, male Sprague Dawley rats were treated chronically with either cocaine or methylphenidate. The rats were examined behaviorally and biochemically at several time points (PND 35, 56, 70 and 90). On PND 56, rats treated with cocaine or methylphenidate from PND 14 through PND 35 exhibited increased hippocampal glial-cell derived neurotrophic factor (GDNF) mRNA levels, after 21 withdrawal days, compared to the saline-treated rats. We found a significant association between cocaine and methylphenidate treatments and age progression in the prefrontal protein expression of brain derived neurotrophic factor (BDNF). Neither treatments affected the behavioral parameters, although acute cocaine administration was associated with increased locomotor activity. It is possible that the increased hippocampal GDNF mRNA levels, may be relevant to the reduced rate of drug seeking behavior in ADHD adolescence that were maintained from childhood on methylphenidate. BDNF protein level increase with age, as well as following stimulant treatments at early age may be relevant to the neurobiology and pharmacotherapy of ADHD. PMID:25576963

  4. 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.

  5. NREM sleep oscillations and brain plasticity in aging

    Directory of Open Access Journals (Sweden)

    Stuart eFogel

    2012-12-01

    Full Text Available The human electroencephalogram (EEG during non-rapid eye movement sleep (NREM is characterized mainly by high-amplitude (> 75 µV, slow-frequency (< 4 Hz waves (slow waves; SW and sleep spindles (~11-15 Hz; > 0.25 s. These NREM oscillations play a crucial role in brain plasticity, and importantly, NREM sleep oscillations change considerably with aging. This review discusses the association between NREM sleep oscillations and cerebral plasticity as well as the functional impact of age-related changes on NREM sleep oscillations. We propose that age-related reduction in sleep-dependent memory consolidation may be due in part to changes in NREM sleep oscillations.

  6. Brain computed tomography findings of aged schizophrenics; Comparison with healthy aged controls and aged schizophrenics with a history of psychosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Oomori, Masao; Koshino, Yoshifumi; Murata, Tetsuhito; Murata, Ichirou; Tani, Kazuhiko; Horie, Tan; Isaki, Kiminori (Fukui Medical School, Matsuoka (Japan))

    1992-05-01

    Brain CT was performed in a total of 30 aged schizophrenic patients, consisting of 20 with no history of psychosurgery (lobotomy) and the other 10 lobotomized patients. The CT findings were compared with those from healthy aged persons. The group of schizophrenic patients had marked atrophy of the frontal lobe and dilatated Sylvian fissure as compared with the control group. There was no significant difference in ventricular factors between the two groups. These findings may have implications for the different mechanisms of the occurrence of atrophied brain surface and enlarged ventricle. The cerebral cortex involved in the occurrence of schizophrenia may be affected by aging-related cerebral atrophy, in addition to the morphological changes due to schizophrenia. Thus, schizophrenic cerebral atrophy was more noticeable than physiological aging-related atrophy. However, enlargement of the ventricle in the schizophrenic group progressed with aging in the same manner as that in the normal group. In comparing schizophrenic patients with or without a history of lobotomy, atrophy of the brain surface and enlargement of the ventricle were more marked in the lobotomized patients than the non-lobotomized patients. This confirmed that lobotomy, as well as surgical scar, is involved in the morphology of schizophrenic brain. (N.K.).

  7. Spontaneous Wheel Running Exercise Induces Brain Recovery via Neurotrophin-3 Expression Following Experimental Traumatic Brain Injury in Rats

    OpenAIRE

    Koo, Hyun Mo; Lee, Sun Min; Kim, Min Hee

    2013-01-01

    [Purpose] The aim of the present study was to investigate the expression of neurotrophin-3 (NT-3) after applying spontaneous wheel running exercises (SWR) after experimental traumatic brain injury (TBI). [Subjects and Methods] Thirty male Sprague-Dawley rats were divided into 3 groups; 20 rats were subjected to controlled cortical impact for TBI, and then, animals were randomly collected from the SWR group and subjected to wheel running exercise for 3 weeks. Ten rats were not subjected to any...

  8. DHA Depletion in Rat Brain Is Associated With Impairment on Spatial Learning and Memory

    Institute of Scientific and Technical Information of China (English)

    YING XIAO; LING WANG; RUO-JUN XU; ZHEN-YU CHEN

    2006-01-01

    Objective To examine the effect of docosahexaenoic acid (DHA) deficiency in brain on spatial learning and memory in rats. Methods Sprague Dawley rats were fed with an n-3 fatty acid deficient diet for two generations to induce DHA depletion in brain. DHA in seven brain regions was analyzed using the gas-liquid chromatography. Morris water maze (MWM) was employed as an assessing index of spatial learning and memory in the n-3 fatty acid deficient adult rats of second generation. Results Feeding an n-3 deficient diet for two generations depleted DHA differently by 39%-63% in the seven brain regions including cerebellum, medulla, hypothalamus, striatum, hippocampus, cortex and midbrain. The MWM test showed that the n-3 deficient rats took a longer time and swam a longer distance to find the escape platform than the n-3 Adq group. Conclusion The spatial learning and memory in adult rats are partially impaired by brain DHA depletion.

  9. Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

    Directory of Open Access Journals (Sweden)

    Khushbu Jain

    2015-01-01

    Full Text Available Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH. The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.

  10. Treadmill exercise induces age and protocol-dependent epigenetic changes in prefrontal cortex of Wistar rats.

    Science.gov (United States)

    Cechinel, Laura Reck; Basso, Carla Giovana; Bertoldi, Karine; Schallenberger, Bruna; de Meireles, Louisiana Carolina Ferreira; Siqueira, Ionara Rodrigues

    2016-10-15

    Some studies have linked age-related beneficial effects of exercise and epigenetic mechanisms. Although, the impact of treadmill exercise on histone acetylation, histone and DNA methylation marks in aged cortices yet remains poorly understood. Considering the role of frontal cortex on brain functions, we investigated the potential of different exercise protocols, single session and daily exercise, to modulate epigenetic marks, namely global H4 acetylation, histone methyltransferase activity (HMT H3K27) and levels of DNA methytransferase (DNMT1 and DNMT3b) in prefrontal cortices from 3 and 21-months aged Wistar rats. The animals were submitted to two treadmill exercise protocols, single session (20min) or daily moderate (20min/day during 14days). The daily exercise protocol induced an increased in histone H4 acetylation levels in prefrontal cortices of 21-months-old rats, without any effects in young adult group. DNMT3b levels were increased in aged cortices of animals submitted to single session of exercise. These results indicate that prefrontal cortex is susceptible to epigenetic changes in a protocol dependent-manner and that H4 acetylation levels and DNMT3b content changes might be linked at least in part to exercise-induced effects on brain functions. PMID:27418438

  11. Detrimental effects of a high fat/high cholesterol diet on memory and hippocampal markers in aged rats.

    Science.gov (United States)

    Ledreux, Aurélie; Wang, Xiuzhe; Schultzberg, Marianne; Granholm, Ann-Charlotte; Freeman, Linnea R

    2016-10-01

    High fat diets have detrimental effects on cognitive performance, and can increase oxidative stress and inflammation in the brain. The aging brain provides a vulnerable environment to which a high fat diet could cause more damage. We investigated the effects of a high fat/high cholesterol (HFHC) diet on cognitive performance, neuroinflammation markers, and phosphorylated Tau (p-Tau) pathological markers in the hippocampus of Young (4-month old) versus Aged (14-month old) male rats. Young and Aged male Fisher 344 rats were fed a HFHC diet or a normal control diet for 6 months. All animals underwent cognitive testing for 12days in a water radial arm maze to assess spatial and working reference memory. Hippocampal tissue was analyzed by immunohistochemistry for structural changes and inflammation, and Western blot analysis. Young and Aged rats fed the HFHC diet exhibited worse performance on a spatial working memory task. They also exhibited significant reduction of NeuN and calbindin-D28k immunoreactivity as well as an increased activation of microglial cells in the hippocampal formation. Western blot analysis of the hippocampus showed higher levels of p-Tau S202/T205 and T231 in Aged HFHC rats, suggesting abnormal phosphorylation of Tau protein following the HFHC diet exposure. This work demonstrates HFHC diet-induced cognitive impairment with aging and a link between high fat diet consumption and pathological markers of Alzheimer's disease.

  12. Detrimental effects of a high fat/high cholesterol diet on memory and hippocampal markers in aged rats.

    Science.gov (United States)

    Ledreux, Aurélie; Wang, Xiuzhe; Schultzberg, Marianne; Granholm, Ann-Charlotte; Freeman, Linnea R

    2016-10-01

    High fat diets have detrimental effects on cognitive performance, and can increase oxidative stress and inflammation in the brain. The aging brain provides a vulnerable environment to which a high fat diet could cause more damage. We investigated the effects of a high fat/high cholesterol (HFHC) diet on cognitive performance, neuroinflammation markers, and phosphorylated Tau (p-Tau) pathological markers in the hippocampus of Young (4-month old) versus Aged (14-month old) male rats. Young and Aged male Fisher 344 rats were fed a HFHC diet or a normal control diet for 6 months. All animals underwent cognitive testing for 12days in a water radial arm maze to assess spatial and working reference memory. Hippocampal tissue was analyzed by immunohistochemistry for structural changes and inflammation, and Western blot analysis. Young and Aged rats fed the HFHC diet exhibited worse performance on a spatial working memory task. They also exhibited significant reduction of NeuN and calbindin-D28k immunoreactivity as well as an increased activation of microglial cells in the hippocampal formation. Western blot analysis of the hippocampus showed higher levels of p-Tau S202/T205 and T231 in Aged HFHC rats, suggesting abnormal phosphorylation of Tau protein following the HFHC diet exposure. This work demonstrates HFHC diet-induced cognitive impairment with aging and a link between high fat diet consumption and pathological markers of Alzheimer's disease. PMID:27343935

  13. Exercise induces mitochondrial biogenesis after brain ischemia in rats.

    Science.gov (United States)

    Zhang, Q; Wu, Y; Zhang, P; Sha, H; Jia, J; Hu, Y; Zhu, J

    2012-03-15

    Stroke is a major cause of death worldwide. Previous studies have suggested both exercise and mitochondrial biogenesis contribute to improved post-ischemic recovery of brain function. However, the exact mechanism underlying this effect is unclear. On the other hand, the benefit of exercise-induced mitochondrial biogenesis in brain has been confirmed. In this study, we attempted to determine whether treadmill exercise induces functional improvement through regulation of mitochondrial biogenesis after brain ischemia. We subjected adult male rats to ischemia, followed by either treadmill exercise or non-exercise and analyzed the effect of exercise on the amount of mitochondrial DNA (mtDNA), expression of mitochondrial biogenesis factors, and mitochondrial protein. In the ischemia-exercise group, only peroxisome proliferator activated receptor coactivator-1 (PGC-1) expression was increased significantly after 3 days of treadmill training. However, after 7 days of training, the levels of mtDNA, nuclear respiratory factor 1, NRF-1, mitochondrial transcription factor A, TFAM, and the mitochondrial protein cytochrome C oxidase subunit IV (COXIV) and heat shock protein-60 (HSP60) also increased above levels observed in non-exercised ischemic animals. These changes followed with significant changes in behavioral scores and cerebral infarct volume. The results indicate that exercise can promote mitochondrial biogenesis after ischemic injury, which may serve as a novel component of exercise-induced repair mechanisms of the brain. Understanding the molecular basis for exercise-induced neuroprotection may be beneficial in the development of therapeutic approaches for brain recovery from the ischemic injury. Based upon our findings, stimulation or enhancement of mitochondrial biogenesis may prove a novel neuroprotective strategy in the future. PMID:22266265

  14. Advanced BrainAGE in older adults with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Katja eFranke

    2013-12-01

    Full Text Available Aging alters brain structure and function and diabetes mellitus (DM may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain MRIs. The Brain Age Gap Estimation (i.e., BrainAGE score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM completed an MRI at 3T, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001, whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034, whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor (TNFα levels, lower verbal fluency scores and more severe depression. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019 and increased fasting blood glucose levels (r = 0.34, p = 0.025. In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2 DM.

  15. Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation

    OpenAIRE

    Basselin, Mireille; Kim, Hyung-Wook; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.; Robert C. Murphy; Farias, Santiago E.

    2010-01-01

    Neuroinflammation, caused by 6 days of intracerebroventricular infusion of a low dose of lipopolysaccharide (LPS; 0.5 ng/h), stimulates brain arachidonic acid (AA) metabolism in rats, but 6 weeks of lithium pretreatment reduces this effect. To further understand this action of lithium, we measured concentrations of eicosanoids and docosanoids generated from AA and docosahexaenoic acid (DHA), respectively, in high-energy microwaved rat brain using LC/MS/MS and two doses of LPS. In rats fed a l...

  16. Prognostic significance of age in traumatic brain injury

    Directory of Open Access Journals (Sweden)

    S S Dhandapani

    2012-01-01

    Full Text Available Background: Age is a strong prognostic factor following traumatic brain injury (TBI, with discrepancies defining the critical prognostic age threshold. This study was undertaken to determine the impact of various age thresholds on outcome after TBI. Materials and Methods : The ages of patients admitted with TBI were prospectively studied in relation to mode of injury, Glasgow coma score (GCS, CT category and surgical intervention. Mortality was assessed at 1 month, and neurological outcome was assessed at 6 months. Appropriate statistical analyzes (details in article were performed. Results: Of the total 244 patients enrolled, 144 patients had severe, 38 patients had moderate and 62 patients had mild TBI, respectively. Age had significant association with grade of injury, CT category and surgical intervention (P 59 years respectively (P 40 years in all subgroups, based on GCS and surgical intervention (P < 0.05. Conclusions : In patients with TBI, age demonstrates independent association with unfavorable outcome at 6 months, in stepwise manner centered on a threshold of 40 years.

  17. Effects of conditioned running on plasma, liver and brain tryptophan and on brain 5-hydroxytryptamine metabolism of the rat.

    OpenAIRE

    Chaouloff, F; Elghozi, J. L.; Guezennec, Y.; Laude, D.

    1985-01-01

    An investigation was made into the effects of conditioned running (1 h and 2 h at 20 m min-1), which accelerates lipolysis, on the concentrations of tryptophan (Trp) in plasma, liver and brain and on 5-hydroxytrptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in brain. Running caused time-dependent increases in plasma free Trp and brain Trp of the rat, leading to increased brain 5-HT turnover as revealed by higher amounts of its metabolite, 5-HIAA. The ratio of brain Trp to plasm...

  18. Effect of exposure to diazinon on adult rat's brain.

    Science.gov (United States)

    Rashedinia, Marzieh; Hosseinzadeh, Hossein; Imenshahidi, Mohsen; Lari, Parisa; Razavi, Bibi Marjan; Abnous, Khalil

    2016-04-01

    Diazinon (DZN), a commonly used agricultural organophosphate insecticide, is one of the major concerns for human health. This study was planned to investigate neurotoxic effects of subacute exposure to DZN in adult male Wistar rats. Animals received corn oil as control and 15 and 30 mg/kg DZN orally by gastric gavage for 4 weeks. The cerebrum malondialdehyde and glutathione (GSH) contents were assessed as biomarkers of lipid peroxidation and nonenzyme antioxidants, respectively. Moreover, activated forms of caspase 3, -9, and Bax/Bcl-2 ratios were evaluated as key apoptotic proteins. Results of this study suggested that chronic administration of DZN did not change lipid peroxidation and GSH levels significantly in comparison with control. Also, the active forms of caspase 3 and caspase 9 were not significantly altered in DZN-treated rat groups. Moreover, no significant changes were observed in Bax and Bcl-2 ratios. This study indicated that generation of reactive oxygen species was probably modulated by intracellular antioxidant system. In conclusion, subacute oral administration of DZN did not alter lipid peroxidation. Moreover, apoptosis induction was not observed in rat brain. PMID:24217015

  19. Age-related changes in brain structural covariance networks

    Directory of Open Access Journals (Sweden)

    Xinwei eLi

    2013-03-01

    Full Text Available Previous neuroimaging studies have suggested that cerebral changes over normal aging are not simply characterized by regional alterations, but rather by the reorganization of cortical connectivity patterns. The investigation of structural covariance networks (SCNs using voxel-based morphometry is an advanced approach to examining the pattern of covariance in gray matter volumes among different regions of the human cortex. To date, how the organization of critical SCNs change during normal aging remains largely unknown. In this study, we used an SCN mapping approach to investigate eight large-scale networks in 240 healthy participants aged 18–89 years. These participants were subdivided into young (18–23 years, middle aged (30–58 years, and older (61–89 years subjects. Eight seed regions were chosen from widely reported functional intrinsic connectivity networks. The voxels showing significant positive associations with these seed regions were used to describe the topological organization of an SCN. All of these networks exhibited non-linear patterns in their spatial extent that were associated with normal aging. These networks, except the primary motor network, had a distributed topology in young participants, a sharply localized topology in middle aged participants, and were relatively stable in older participants. The structural covariance derived using the primary motor cortex was limited to the ipsilateral motor regions in the young and older participants, but included contralateral homologous regions in the middle aged participants. In addition, there were significant between-group differences in the structural networks associated with language-related speech and semantics processing, executive control, and the default-mode network. Taken together, the results of this study demonstrate age-related changes in the topological organization of SCNs, and provide insights into normal aging of the human brain.

  20. Neuroprotective effect ofShenqi Fuzheng injection pretreatment in aged rats with cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Ying-min Cai; Yong Zhang; Peng-bo Zhang; Lu-ming Zhen; Xiao-ju Sun; Zhi-ling Wang; Ren-yan Xu; Rong-liang Xue

    2016-01-01

    Shenqi Fuzheng injection is extracted from the Chinese herbsRadix Astragali andRadix Codonopsis. The aim of the present study was to investigate the neuroprotective effects of Shenqi Fuzheng injection in cerebral ischemia and reperfusion. Aged rats (20–22 months) were divided into three groups: sham, model, and treatment.Shenqi Fuzheng injection or saline (40 mL/kg) was injected into the tail vein daily for 1 week, after which a cerebral ischemia/reperfusion injury model was established. Compared with model rats that received saline, rats in the treatment group had smaller infarct volumes, lower brain water and malondialdehyde content, lower brain Ca2+levels, lower ac-tivities of serum lactate dehydrogenase and creatine kinase, and higher superoxide dismutase activity. In addition, the treatment group showed less damage to the brain tissue ultrastructure and better neurological function. Our ifndings indicate thatShenqi Fuzheng injec-tion exerts neuroprotective effects in aged rats with cerebral ischemia/reperfusion injury, and that the underlying mechanism relies on oxygen free radical scavenging and inhibition of brain Ca2+ accumulation.

  1. Environmental enrichment promotes neural remodeling in newborn rats with hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Chuanjun Liu; Yankui Guo; Yalu Li; Zhenying Yang

    2011-01-01

    We evaluated the effect of hypoxic-ischemic brain damage and treatment with early environmental enrichment intervention on development of newborn rats, as evaluated by light and electron microscopy and morphometry. Early intervention with environmental enrichment intelligence training attenuated brain edema and neuronal injury, promoted neuronal repair, and increased neuronal plasticity in the frontal lobe cortex of the newborn rats with hypoxic-ischemic brain damage.

  2. Spontaneous Object Recognition Memory in Aged Rats: Complexity versus Similarity

    Science.gov (United States)

    Gamiz, Fernando; Gallo, Milagros

    2012-01-01

    Previous work on the effect of aging on spontaneous object recognition (SOR) memory tasks in rats has yielded controversial results. Although the results at long-retention intervals are consistent, conflicting results have been reported at shorter delays. We have assessed the potential relevance of the type of object used in the performance of…

  3. Continuous and simultaneous electrochemical measurements of glucose, lactate, and ascorbate in rat brain following brain ischemia.

    Science.gov (United States)

    Lin, Yuqing; Yu, Ping; Hao, Jie; Wang, Yuexiang; Ohsaka, Takeo; Mao, Lanqun

    2014-04-15

    Developing new tools and technologies to enable recording the dynamic changes of multiple neurochemicals is the essence of better understanding of the molecular basis of brain functions. This study demonstrates a microfluidic chip-based online electrochemical system (OECS) for in vivo continuous and simultaneous monitoring of glucose, lactate, and ascorbate in rat brain. To fabricate the microfluidic chip-based detecting system, a microfluidic chip with patterned channel is developed into an electrochemical flow cell by incorporating the chip with three surface-modified indium-tin oxide (ITO) electrodes as working electrodes, a Ag/AgCl wire as reference electrode, and a stainless steel tube as counter electrode. Selective detection of ascorbate is achieved by the use of single-walled carbon nanotubes (SWNTs) to largely facilitate the electrochemical oxidation of ascorbate, while a dehydrogenase-based biosensing mechanism with methylene green (MG) adsorbed onto SWNTs as an electrocatalyst for the oxidation of dihydronicotiamide adenine dinucleotide (NADH) is employed for biosensing of glucose and lactate. To avoid the crosstalk among three sensors, the sensor alignment is carefully designed with the SWNT-modified electrode in the upstream channel and paralleled glucose and lactate biosensors in the downstream channels. With the microfluidic chip-based electrochemical flow cell as the detector, an OECS is successfully established by directly integrating the microfluidic chip-based electrochemical flow cell with in vivo microdialysis. The OECS exhibits a good linear response toward glucose, lactate, and ascorbate with less crosstalk. This property, along with the high stability and selectivity, enables the OECS for continuously monitoring three species in rat brain following brain ischemia. PMID:24621127

  4. Stereological brain volume changes in post-weaned socially isolated rats

    DEFF Research Database (Denmark)

    Fabricius, Katrine; Helboe, Lone; Steiniger-Brach, Björn;

    2010-01-01

    Lister Hooded rats isolated from postnatal day 25 for 15 weeks. We observed the expected gender differences in total brain volume with males having larger brains than females. Further, we found that isolated males had significantly smaller brains than group-housed controls and larger lateral ventricles...

  5. Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

    Science.gov (United States)

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

  6. The establishment of brain radiation injury experimental model of SD rats with whole brain irradiation in wakefulness

    International Nuclear Information System (INIS)

    Objective: To establish the brain radiation injury experimental model of Sprague-Dawley (SD) rat being irradiated in wakefulness so that the side effects from the anesthetics can be eliminated. Methods: Experiment animals were divided into 4 groups randomly according to the difference of radiation dose. Each group involved 25 rats. 'Thermoplastic material fixing cage' was used to keep rats in wakefulness during irradiation. The whole brains of SD rats were irradiated by 4 MeV electron beam at a single dose of 0 Gy, 2 Gy, 15 Gy and 30 Gy, which was measured by therapy beam analyser and dosimeter. The scores of gross neurological symptoms and changes in body weight were sequentially evaluated twice every week after irradiation. The examination of the head skin inside the field was performed as well. The changes of the nerve cell in the hippocampus region of rats with the Hematoxylin-eosin (HE) staining were observed at the time of 6 hours, 1 day, 1 week and 1 month after irradiation. Results: The peak dosage depth of 4 MeV electron beam was 14.3 mm, and the dosimetry homogeneity of the radiation field was within 5%. The dose attenuation rate was less than 2.57% because of the thermoplastic material fixing cage. Intra-portal alopecia was observed in all the rats exposed to radiation at the dose of 30 Gy and in some of the rats exposed to radiation at the dose of 15 Gy. There was no significant difference in increasing trend of body weight and the score changes of the gross neurological symptoms in all groups. The obvious lesion was observed in the hippocampus region of rats after 30 Gy irradiated. Conclusion: The brain radiation injury experimental model of SD rat in wakefulness with whole brain radiation eliminates the side effects from the anesthetic. It appears to be an excellent model for studying on the brain radiation injury in the early stage

  7. Accelerated leucine decarboxylation in the rat brain in relation to increased blood ammonia levels during acute hepatic failure.

    Directory of Open Access Journals (Sweden)

    Shiota,Tetsuya

    1984-06-01

    Full Text Available Leucine decarboxylation in rat brain was investigated during acute hepatic failure, induced by partial hepatectomy after carbon tetrachloride (CCl4 pretreatment of rats. These rats presented metabolic alkalosis, and had significantly higher levels of arterial blood and brain ammonia than control and CCl4-treated rats. Brain leucine decarboxylation was elevated in rats with hepatic failure. This alteration correlated with arterial blood ammonia concentrations, and probably with elevated brain ammonia levels, as brain ammonia levels were directly related to arterial blood ammonia.

  8. Age sensitivity of behavioral tests and brain substrates of normal aging in mice.

    Science.gov (United States)

    Kennard, John A; Woodruff-Pak, Diana S

    2011-01-01

    Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE) in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

  9. Age Sensitivity of Behavioral Tests and Brain Substrates of Normal Aging in Mice

    Directory of Open Access Journals (Sweden)

    John A. Kennard

    2011-05-01

    Full Text Available Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

  10. Oxidative stress of brain and liver is increased by Wi-Fi (2.45GHz) exposure of rats during pregnancy and the development of newborns.

    Science.gov (United States)

    Çelik, Ömer; Kahya, Mehmet Cemal; Nazıroğlu, Mustafa

    2016-09-01

    An excessive production of reactive oxygen substances (ROS) and reduced antioxidant defence systems resulting from electromagnetic radiation (EMR) exposure may lead to oxidative brain and liver damage and degradation of membranes during pregnancy and development of rat pups. We aimed to investigate the effects of Wi-Fi-induced EMR on the brain and liver antioxidant redox systems in the rat during pregnancy and development. Sixteen pregnant rats and their 48 newborns were equally divided into control and EMR groups. The EMR groups were exposed to 2.45GHz EMR (1h/day for 5 days/week) from pregnancy to 3 weeks of age. Brain cortex and liver samples were taken from the newborns between the first and third weeks. In the EMR groups, lipid peroxidation levels in the brain and liver were increased following EMR exposure; however, the glutathione peroxidase (GSH-Px) activity, and vitamin A, vitamin E and β-carotene concentrations were decreased in the brain and liver. Glutathione (GSH) and vitamin C concentrations in the brain were also lower in the EMR groups than in the controls; however, their concentrations did not change in the liver. In conclusion, Wi-Fi-induced oxidative stress in the brain and liver of developing rats was the result of reduced GSH-Px, GSH and antioxidant vitamin concentrations. Moreover, the brain seemed to be more sensitive to oxidative injury compared to the liver in the development of newborns.

  11. Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

    Science.gov (United States)

    Figueira, R.L.; Gonçalves, F.L.; Simões, A.L.; Bernardino, C.A.; Lopes, L.S.; Castro e Silva, O.; Sbragia, L.

    2016-01-01

    Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC). This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group): 1) preterm control (PTC), 2) preterm ventilated (PTV), 3) preterm asphyxiated (PTA), 4) preterm asphyxiated and ventilated (PTAV), 5) term control (TC), 6) term ventilated (TV), 7) term asphyxiated (TA), and 8) term asphyxiated and ventilated (TAV). We measured body, brain, and intestine weights and respective ratios [(BW), (BrW), (IW), (BrW/BW) and (IW/BW)]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus) and intestine (jejunum/ileum) tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP). IW was lower in the TA than in the other terms (Pmechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers. PMID:27356106

  12. The Effect of the APOE Genotype on Individual BrainAGE in Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease.

    Science.gov (United States)

    Löwe, Luise Christine; Gaser, Christian; Franke, Katja

    2016-01-01

    In our aging society, diseases in the elderly come more and more into focus. An important issue in research is Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) with their causes, diagnosis, treatment, and disease prediction. We applied the Brain Age Gap Estimation (BrainAGE) method to examine the impact of the Apolipoprotein E (APOE) genotype on structural brain aging, utilizing longitudinal magnetic resonance image (MRI) data of 405 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We tested for differences in neuroanatomical aging between carrier and non-carrier of APOE ε4 within the diagnostic groups and for longitudinal changes in individual brain aging during about three years follow-up. We further examined whether a combination of BrainAGE and APOE status could improve prediction accuracy of conversion to AD in MCI patients. The influence of the APOE status on conversion from MCI to AD was analyzed within all allelic subgroups as well as for ε4 carriers and non-carriers. The BrainAGE scores differed significantly between normal controls, stable MCI (sMCI) and progressive MCI (pMCI) as well as AD patients. Differences in BrainAGE changing rates over time were observed for APOE ε4 carrier status as well as in the pMCI and AD groups. At baseline and during follow-up, BrainAGE scores correlated significantly with neuropsychological test scores in APOE ε4 carriers and non-carriers, especially in pMCI and AD patients. Prediction of conversion was most accurate using the BrainAGE score as compared to neuropsychological test scores, even when the patient's APOE status was unknown. For assessing the individual risk of coming down with AD as well as predicting conversion from MCI to AD, the BrainAGE method proves to be a useful and accurate tool even if the information of the patient's APOE status is missing. PMID:27410431

  13. Hemispherical dominance of glucose metabolic rate in the brain of the 'normal' ageing population

    NARCIS (Netherlands)

    Cutts, DA; Maguire, RP; Leenders, KL; Spyrou, NM

    2004-01-01

    In the 'normal' ageing brain a decrease in the cerebral metabolic rate has been determined across many brain regions. This study determines whether age differences would affect metabolic rates in regions and different hemispheres of the brain. The regional metabolic rate of glucose (rCMRGlu) was exa

  14. Cerebrolysin improves memory and ameliorates neuronal atrophy in spontaneously hypertensive, aged rats.

    Science.gov (United States)

    Solis-Gaspar, Carlos; Vazquez-Roque, Ruben A; De Jesús Gómez-Villalobos, Ma; Flores, Gonzalo

    2016-09-01

    The spontaneously hypertensive (SH) rat has been used as an animal model of vascular dementia (VD). Our previous report showed that, SH rats exhibited dendritic atrophy of pyramidal neurons of the CA1 dorsal hippocampus and layers 3 and 5 of the prefrontal cortex (PFC) at 8 months of age. In addition, we showed that cerebrolysin (Cbl), a neurotrophic peptide mixture, reduces the dendritic atrophy in aged animal models. This study aimed to determine whether Cbl was capable of reducing behavioral and neuronal alterations, in old female SH rats. The level of diastolic and systolic pressure was measured every month for the 6 first months and only animals with more than 160 mm Hg of systolic pressure were used. Female SH rats (6 months old) received 6 months of Cbl treatment. Immediately after the Cbl treatment, two behavioral tests were applied, the Morris water maze test for memory and learning and locomotor activity in novel environments. Immediately after the last behavioral test, dendritic morphology was studied with the Golgi-Cox stain procedure followed by a Sholl analysis. Clearly, SH rats with Cbl showed an increase in the dendritic length and dendritic spine density of pyramidal neurons in the CA1 in the dorsal hippocampus and layers 3 and 5 of the PFC. Interestingly, Cbl improved memory of the old SH rats. Our results support the possibility that Cbl may have beneficial effects on the management of brain alterations in an animal model with VD. Synapse 70:378-389, 2016. © 2016 Wiley Periodicals, Inc. PMID:27164468

  15. Sex Differences in Serotonin 1 Receptor Binding in Rat Brain

    Science.gov (United States)

    Fischette, Christine T.; Biegon, Anat; McEwen, Bruce S.

    1983-10-01

    Male and female rats exhibit sex differences in binding by serotonin 1 receptors in discrete areas of the brain, some of which have been implicated in the control of ovulation and of gonadotropin release. The sex-specific changes in binding, which occur in response to the same hormonal (estrogenic) stimulus, are due to changes in the number of binding sites. Castration alone also affects the number of binding sites in certain areas. The results lead to the conclusion that peripheral hormones modulate binding by serotonin 1 receptors. The status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.

  16. Label-free dopamine imaging in live rat brain slices.

    Science.gov (United States)

    Sarkar, Bidyut; Banerjee, Arkarup; Das, Anand Kant; Nag, Suman; Kaushalya, Sanjeev Kumar; Tripathy, Umakanta; Shameem, Mohammad; Shukla, Shubha; Maiti, Sudipta

    2014-05-21

    Dopaminergic neurotransmission has been investigated extensively, yet direct optical probing of dopamine has not been possible in live cells. Here we image intracellular dopamine with sub-micrometer three-dimensional resolution by harnessing its intrinsic mid-ultraviolet (UV) autofluorescence. Two-photon excitation with visible light (540 nm) in conjunction with a non-epifluorescent detection scheme is used to circumvent the UV toxicity and the UV transmission problems. The method is established by imaging dopamine in a dopaminergic cell line and in control cells (glia), and is validated by mass spectrometry. We further show that individual dopamine vesicles/vesicular clusters can be imaged in cultured rat brain slices, thereby providing a direct visualization of the intracellular events preceding dopamine release induced by depolarization or amphetamine exposure. Our technique opens up a previously inaccessible mid-ultraviolet spectral regime (excitation ~270 nm, emission free imaging of native molecules in live tissue.

  17. 脑血流低灌注老龄大鼠中脑皮质血流的改变与血清总胆固醇和高密度脂蛋白的动态变化%Dynamic changes of cortical blood flow and serum total cholesterol and high density lipoprotein in brains of aging rat during cerebral hypoperfusion

    Institute of Scientific and Technical Information of China (English)

    王林辉; 田茗源; 滕志朋; 王晨; 李昱

    2012-01-01

    目的:通过建立脑血流低灌注模型,观察老龄大鼠脑血流的变化以及在脑血流低灌注下血清中总胆固醇(Total cholesterol,TC)和高密度脂蛋白(High density lipoprotein,HDL)的动态变化.方法:采用持久性双侧颈总动脉结扎法(2Vo)致老龄大鼠脑血流灌注不足,测定术后7、14、21、28d大鼠脑皮质血流;检测、比较术后不同时间段大鼠血清中TC和HDL浓度差异.结果:术后第14天大鼠脑颞区血流出现明显减少;术后21、28d大鼠脑局部皮质血管有再生侧支形成,大鼠脑颞区血流仍未恢复;术后第14天血清中HDL、TC含量明显高于假手术组(P<0.05),随着缺血时间延长,又逐渐降低.结论:血清TC和HDL浓度在脑缺血灌注不足的不同时间段经历了先增强后减弱的动态变化,提示脑血流低灌注老龄大鼠因大脑血流灌注不足可出现体内胆固醇代谢失衡并出现应激调节现象.%Objective: To investigate the change of cortical blood flow and the dynamic changes of serum total cholesterol(TC ) and high density lipoprotein(HDL) in brains of aging rat during cerebral ischemic injury. Methods:The model of aging rats with cerebral hy-poperfusion was successfully constructed by persistent bilateral common carotid artery ligation(2V0). The cortical blood flow and the concentration of serum TC and HDL at different time points were determined and compared. Results: Compared with the sham-operated group,the temporal blood flow was significantly decreased in 14 d group. But the collateral vessels were gradually regenerated and formed in local brain,while the temporal blood flow was restored in 21 d and 28 d group. The concentration of HDL and TC was significantly higher in 14 d group than in the sham-operated group (P<0.05), and both of them were decreased with the extention of ischemia time. Conclusions:The serum TC and HDL concentration undergo dynamic changes-increasing first and then decreasing during the process

  18. Effects of extremely low frequency magnetic field on oxidative balance in brain of rats.

    Science.gov (United States)

    Ciejka, Elzbieta; Kleniewska, P; Skibska, B; Goraca, A

    2011-12-01

    Extremely low frequency magnetic field (ELF-MF) may result in oxidative DNA damage and lipid peroxidation with an ultimate effect on a number of systemic disturbances and cell death. The aim of the study is to assess the effect of ELF-MF parameters most frequently used in magnetotherapy on reactive oxygen species generation (ROS) in brain tissue of experimental animals depending on the time of exposure to this field. The research material included adult male Sprague-Dawley rats, aged 3-4 months. The animals were divided into 3 groups: I - control (shame) group; II - exposed to the following parameters of the magnetic field: 7 mT, 40 Hz, 30 min/day, 10 days; III - exposed to the ELF-MF parameters of 7 mT, 40 Hz, 60 min/day, 10 days. The selected parameters of oxidative stress: thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), total free sulphydryl groups (-SH groups) and protein in brain homogenates were measured after the exposure of rats to the magnetic field. ELF-MF parameters of 7 mT, 40 Hz, 30 min/day for 10 days caused a significant increase in lipid peroxidation and insignificant increase in H(2)O(2) and free -SH groups. The same ELF-MF parameters but applied for 60 min/day caused a significant increase in free -SH groups and protein concentration in the brain homogenates indicating the adaptive mechanism. The study has shown that ELF-MF applied for 30 min/day for 10 days can affect free radical generation in the brain. Prolongation of the exposure to ELF-MF (60/min/day) caused adaptation to this field. The effect of ELF-MF irradiation on oxidative stress parameters depends on the time of animal exposure to magnetic field. PMID:22314568

  19. Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state.

    Science.gov (United States)

    Briones, T L; Darwish, H

    2014-03-14

    In the present study we examined whether vitamin D supplementation can reduce age-related tau hyperphosphorylation and cognitive impairment by enhancing brain energy homeostasis and protein phosphatase 2A (PP2A) activity, and modulating the redox state. Male F344 rats aged 20 months (aged) and 6 months (young) were randomly assigned to either vitamin D supplementation or no supplementation (control). Rats were housed in pairs and the supplementation group (n=10 young and n=10 aged) received subcutaneous injections of vitamin D (1, α25-dihydroxyvitamin D3) for 21 days. Control animals (n=10 young and n=10 aged) received equal volume of normal saline and behavioral testing in the water maze started on day 14 after the initiation of vitamin D supplementation. Tau phosphorylation, markers of brain energy metabolism (ADP/ATP ratio and adenosine monophosphate-activated protein kinase) and redox state (levels of reactive oxygen species, activity of superoxide dismutase, and glutathione levels) as well as PP2A activity were measured in hippocampal tissues. Our results extended previous findings that: (1) tau phosphorylation significantly increased during aging; (2) markers of brain energy metabolism and redox state are significantly decreased in aging; and (3) aged rats demonstrated significant learning and memory impairment. More importantly, we found that age-related changes in brain energy metabolism, redox state, and cognitive function were attenuated by vitamin D supplementation. No significant differences were seen in tau hyperphosphorylation, markers of energy metabolism and redox state in the young animal groups. Our data suggest that vitamin D ameliorated the age-related tau hyperphosphorylation and cognitive decline by enhancing brain energy metabolism, redox state, and PP2A activity making it a potentially useful therapeutic option to alleviate the effects of aging.

  20. The primary structure of rat brain (cytoplasmic) dynein heavy chain, a cytoplasmic motor enzyme.

    OpenAIRE

    Zhang, Z.; Tanaka, Y.; Nonaka, S; Aizawa, H.; Kawasaki, H; Nakata, T; Hirokawa, N

    1993-01-01

    Overlapping cDNA clones encoding the heavy chain of rat brain cytoplasmic dynein have been isolated. The isolated cDNA clones contain an open reading frame of 13,932 bp encoding 4644 aa (M(r), 532,213). The deduced protein sequence of the heavy chain of rat brain dynein shows significant similarity to sea urchin flagellar beta-dynein (27.0% identical) and to Dictyostelium cytoplasmic dynein (53.5% identical) throughout the entire sequence. The heavy chain of rat brain (cytoplasmic) dynein con...

  1. Effects of Atorvastatin on the Hypertension-Induced Oxidative Stress in the Rat Brain

    OpenAIRE

    Mohammadi, Mohammad Taghi; Amini, Reza; Jahanbakhsh, Zahra; Shekarforoush, Shahnaz

    2013-01-01

    Background: It is well known that the development of brain oxidative stress is one of the most serious complications of arterial hypertension that evokes brain tissue damage. The aim of this study was to examine the effects of atorvastatin treatment (20 mg/kg/day), as an antioxidant, to prevent the brain tissue oxidative stress in the hypertensive (HTN) rats. Methods: Experiments were performed in four groups of rats (n = 5 each group): sham, sham-treated, HTN and HTN treated. Rats were made ...

  2. Adenovirally Delivered Brain-derived Neurotrophic Factor to Rat Retina

    Institute of Scientific and Technical Information of China (English)

    Xu Hou; Dan Hu; Yannian Hui

    2004-01-01

    Purpose: To study the expression of brain-derived neurotrophic factor (BDNF) in the rat retina delivered by adenovirus.Methods: Adenovirus with BDNF gene was injected into the vitreous. Gene expression was detected by immunofluorescence staining, and quantitative analysis was performed after injury and transfection by Enzyme-linked immunosorbent assay (ELISA).Results: The positive cells can be seen on the 3rd day and last 4 weeks by immunofluorescence staining. Positive cells in the control group were fewer than those in the transfection group or the fluorescence intensity was lower at every time point. Quantitative analysis showed that the expression of BDNF groups was higher than that of the control group at every time point(P < 0.01 ), and that of the injured group without transfection was higher than that of the control group on the 3rd day and the 7th day (P < 0.01 ).Conclusion: Efficient and stable transfer of BDNF gene could be achieved by adenovirus delivery into the retina of rats. Injury can promote the expression of BDNF in early period.

  3. Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats

    DEFF Research Database (Denmark)

    Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne;

    2014-01-01

    Ammonia has a key role in the development of hepatic encephalopathy (HE). In the brain, glutamine synthetase (GS) rapidly converts blood-borne ammonia into glutamine which in high concentrations may cause mitochondrial dysfunction and osmolytic brain edema. In astrocyte-neuron cocultures and brains...... of healthy rats, inhibition of GS by methionine sulfoximine (MSO) reduced glutamine synthesis and increased alanine synthesis. Here, we investigate effects of MSO on brain and interorgan ammonia metabolism in sham and bile duct ligated (BDL) rats. Concentrations of glutamine, glutamate, alanine......, and aspartate and incorporation of (15)NH4(+) into these amino acids in brain, liver, muscle, kidney, and plasma were similar in sham and BDL rats treated with saline. Methionine sulfoximine reduced glutamine concentrations in liver, kidney, and plasma but not in brain and muscle; MSO reduced incorporation...

  4. Effects of age on spatial information processing: relationship to senescent changes in brain noradrenergic and opioid systems

    Energy Technology Data Exchange (ETDEWEB)

    Rapp, P.R.

    1985-01-01

    A major focus in current research on aging is the identification of senescent changes in cognitive function in laboratory animals. This literature indicates that the processing of spatial information may be particularly impaired during senescence. The degree to which nonspecific factors (eg. sensory of motor deficits) contribute to behavioral impairments in aging, however, remains largely uninvestigated. In addition, few studies have attempted to identify senescent changes in brain structure and function which might underlie the behavioral manifestations of aging. In the behavioral experiments reported here, the authors tested young, middle-age, and senescent rates in several versions of a spatial memory task, the Morris water maze. The results of these investigations demonstrate that aged rats are significantly impaired in the Morris task compared to young or middle-age animals. In addition, these studies indicate that age-related deficits in the water maze reflect a specific dysfunction in the ability of older animals to effectively process spatial information rather than a senescent decline in sensory or motor functions. Using the subjects from the behavioral studies, additional investigations assessed whether age-dependent changes in neurochemical and neuroanatomical systems which are known to mediate spatial learning in young animals were related to the behavioral deficits exhibited by aged rats. The results of these studies demonstrate that a portion of senescent animals exhibit significant increases in lateral septal /sup 3/H-desmethylimipramine binding and decrease in /sup 3/H-naloxone binding in this same region as assessed by quantitative in vitro autoradiography.

  5. Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation: an intravital microscopic study

    OpenAIRE

    Rafael Simas; Paulina Sannomiya; José Walber M. C Cruz; Cristiano de Jesus Correia; Fernando Luiz Zanoni; Maurício Kase; Laura Menegat; Isaac Azevedo Silva; Moreira, Luiz Felipe P.

    2012-01-01

    OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death–associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma. METHOD: Brain death was induced using intracranial balloon inflatio...

  6. AGES in brain ageing: AGE-inhibitors as neuroprotective and anti-dementia drugs?

    Science.gov (United States)

    Dukic-Stefanovic, S; Schinzel, R; Riederer, P; Münch, G

    2001-01-01

    In Alzheimer's disease, age-related cellular changes such as compromised energy production and increased radical formation are worsened by the presence of AGEs as additional, AD specific stress factors. Intracellular AGEs (most likely derived from methylglyoxal) crosslink cytoskeletal proteins and render them insoluble. These aggregates inhibit cellular functions including transport processes and contribute to neuronal dysfunction and death. Extracellular AGEs, which accumulate in ageing tissue (but most prominently on long-lived protein deposits like the senile plaques) exert chronic oxidative stress on neurons. In addition, they activate glial cells to produce free radicals (superoxide and NO) and neurotoxic cytokines such as TNF-alpha. Drugs, which inhibit the formation of AGEs by specific chemical mechanisms (AGE-inhibitors), including aminoguanidine, carnosine, tenilsetam, OPB-9195 and pyridoxamine, attenuate the development of (AGE-mediated) diabetic complications. Assuming that 'carbonyl stress' contributes significantly to the progression of Alzheimer's disease, AGE-inhibitors might also become interesting novel therapeutic drugs for treatment of AD. PMID:11708614

  7. [POLYPEPTIDES INFLUENCE ON TISSUE CELL CULTURES REGENERATION OF VARIOUS AGE RATS].

    Science.gov (United States)

    Ryzhak, A P; Chalisova, N I; Lin'kova, N S; Khalimov, R I; Ryzhak, G A; Zhekalov, A N

    2015-01-01

    A comparative study of polypeptides extracted from the tissues of calves: Cortexin (from brain cortex), Epinorm (from pineal gland), Ventvil (from liver), Prostatilen (from prostate), Thymalin (from thymus), Chelohart (from heart), Chondrolux (from cartilage) on the relevant organotypic tissue cultures of young and old rats, in concentration 0,01-100 ng/ml was performed. Polypeptides specifically stimulated "young" and "old" cell cultures growth in concentration 20-50 ng/ml. This effect correlates with increasing of PCNA and decreasing of p53 expression in brain cortex, pineal gland, liver, prostate, heart, cartilage. Moreover, Thymalin activated CD5, CD20 expression--markers of B-cells differentiation. These data show that polypeptides isolated from different tissues have selective molecular activity on the regeneration of suitable tissues in aging.

  8. A better mild traumatic brain injury model in the rat.

    Science.gov (United States)

    Takeuchi, Satoru; Nawashiro, Hiroshi; Sato, Shunichi; Kawauchi, Satoko; Nagatani, Kimihiro; Kobayashi, Hiroaki; Otani, Naoki; Osada, Hideo; Wada, Kojiro; Shima, Katsuji

    2013-01-01

    The primary pathology associated with mild -traumatic brain injury (TBI) is selective axonal injury, which may characterize the vast majority of blast-induced TBIs. Axonal injuries in cases of mild TBI have been considered to be the main factors responsible for the long-lasting memory or attentional impairment in affected subjects. Among these axonal injuries, recent attention has been focused on the cingulum bundle (CB). Furthermore, recent studies with diffusion tensor MR imaging have shown the presence of injuries of the CB in cases of mild TBI in humans. This study aimed to provide a better laboratory model of mild TBI.Sprague-Dawley rats were subjected to mild TBI using laser-induced shock waves (LISW) (sham, 0.5 J/cm(2), or 1.0 J/cm(2); n = 4 per group). Bodian-stained brain sections 14 days after LISW at 0.5 J/cm(2) or 1.0 J/cm(2) showed a decrease in the CB axonal density compared with the sham group, whereas there were no differences in the axonal density of the corpus callosum.The present study shows that this model is capable of reproducing the histological changes associated with mild TBI. PMID:23564112

  9. Cyclosporin safety in a simplified rat brain tumor implantation model

    Directory of Open Access Journals (Sweden)

    Francisco H. C. Felix

    2012-01-01

    Full Text Available Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate. This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

  10. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Christian Gaser

    Full Text Available Alzheimer's disease (AD, the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI-based biomarker that predicts the individual progression of mild cognitive impairment (MCI to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%. The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF. With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07-1.13]. Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options.

  11. Subcellular localization and compartmentation of thiamine derivatives in rat brain.

    Science.gov (United States)

    Bettendorff, L; Wins, P; Lesourd, M

    1994-05-26

    The subcellular distribution of thiamine derivatives in rat brain was studied. Thiamine diphosphate content was highest in the mitochondrial and synaptosomal fractions, and lowest in microsomal, myelin and cytosolic fractions. Only 3-5% of total thiamine diphosphate was bound to transketolase, a cytosolic enzyme. Thiamine triphosphate was barely detectable in the microsomal and cytosolic fraction, but synaptosomes were slightly enriched in this compound compared to the crude homogenate. Both myelin and mitochondrial fractions contained significant amounts of thiamine triphosphate. In order to estimate the relative turnover rates of these compounds, the animals received an intraperitoneal injection of either [14C]thiamine or [14C]sulbutiamine (isobutyrylthiamine disulfide) 1 h before decapitation. The specific radioactivities of thiamine compounds found in the brain decreased in the order: thiamine > thiamine triphosphate > thiamine monophosphate > thiamine diphosphate. Incorporation of radioactivity into thiamine triphosphate was more marked with [14C]sulbutiamine than with [14C]thiamine. The highest specific radioactivity of thiamine diphosphate was found in the cytosolic fraction of the brain, though this pool represents less than 10% of total thiamine diphosphate. Cytosolic thiamine diphosphate had a twice higher specific radioactivity when [14C]sulbutiamine was used as precursor compared with thiamine though no significant differences were found in the other cellular compartments. Our results suggest the existence of two thiamine diphosphate pools: the bound cofactor pool is essentially mitochondrial and has a low turnover; a much smaller cytosolic pool (6-7% of total TDP) of high turnover is the likely precursor of thiamine triphosphate. PMID:8186256

  12. Prion protein accumulation in lipid rafts of mouse aging brain.

    Directory of Open Access Journals (Sweden)

    Federica Agostini

    Full Text Available The cellular form of the prion protein (PrP(C is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be sporadic, genetic or infectious. Sporadic prion diseases are the most common form mainly affecting aging people. In this work, we investigate the biochemical environment in which sporadic prion diseases may develop, focusing our attention on the cell membrane of neurons in the aging brain. It is well established that with aging the ratio between the most abundant lipid components of rafts undergoes a major change: while cholesterol decreases, sphingomyelin content rises. Our results indicate that the aging process modifies the compartmentalization of PrP(C. In old mice, this change favors PrP(C accumulation in detergent-resistant membranes, particularly in hippocampi. To confirm the relationship between lipid content changes and PrP(C translocation into detergent-resistant membranes (DRMs, we looked at PrP(C compartmentalization in hippocampi from acid sphingomyelinase (ASM knockout (KO mice and synaptosomes enriched in sphingomyelin. In the presence of high sphingomyelin content, we observed a significant increase of PrP(C in DRMS. This process is not due to higher levels of total protein and it could, in turn, favor the onset of sporadic prion diseases during aging as it increases the PrP intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease-resistant PrP formation. This may suggest an involvement of PrP lipid environment in prion formation and consequently it may play a role in the onset or development of sporadic forms of prion diseases.

  13. Tannic acid alleviates lead acetate-induced neurochemical perturbations in rat brain.

    Science.gov (United States)

    Ashafaq, Mohammad; Tabassum, Heena; Vishnoi, Shruti; Salman, Mohd; Raisuddin, Sheikh; Parvez, Suhel

    2016-03-23

    Oxidative stress has been projected as a promising mechanism involved in lead exposure. The lead predisposition catalyzes oxidative reactions and generates reactive oxygen species. The present study was carried out to investigate the effect of oral administration of tannic acid (TA) on behavioral deficit, antioxidative deterioration induced by lead acetate (LA) exposure on experimental rat brain. Male Wistar rats were treated with 50mg/kg body weight of LA and TA for three times a week for two weeks. Our data showed LA-induced profound elevation of ROS production and oxidative stress, as evidenced by increased levels of oxidative stress markers such as lipid peroxidation and protein carbonyl observed in LA treated rats, whereas significant depletion in the activity of non-enzymatic antioxidants, enzymatic antioxidants, neurotoxicity biomarker and histological changes were observed in LA treated rat brain. However, TA administration restored antioxidant status of brain significantly when compared to control. Our results demonstrate that TA exhibits potent antioxidant properties and suppresses oxidative damages in rat brain induced by LA treatment. These findings were further supported by the neurotoxicity biomarker and histopathological findings in the brain tissue showed that TA protected tissue from deleterious effects of LA exposure. It is concluded, these data suggest that LA induces oxidative stress and supplementation of TA has a powerful antioxidant effect, and it protected rat brain from poisonous effect of LA exposure in experimental rat.

  14. The effects of ecstasy (MDMA on brain serotonin transporters are dependent on age-of-first exposure in recreational users and animals.

    Directory of Open Access Journals (Sweden)

    Anne Klomp

    Full Text Available RATIONALE AND OBJECTIVE: Little is known on the effects of ecstasy (MDMA, a potent 5-HT-releaser and neurotoxin exposure on brain development in teenagers. The objective of this study was to investigate whether in humans, like previous observations made in animals, the effects of MDMA on the 5-HT system are dependent on age-of-first exposure. METHODS: 5-HT transporter (SERT densities in the frontal cortex and midbrain were assessed with [(123I]β-CIT single photon emission computed tomography in 33 users of ecstasy. Subjects were stratified for early-exposed users (age-at-first exposure 14-18 years; developing brain, and late-exposed users (age-at-first exposure 18-36 years; mature brain. In parallel, we investigated the effects of age experimentally with MDMA in early-exposed (adolescent rats and late-exposed (adult rats using the same radioligand. RESULTS: On average, five years after first exposure, we found a strong inverse relationship, wherein age-at-first exposure predicted 79% of the midbrain SERT variability in early (developing brain exposed ecstasy users, whereas this was only 0.3% in late (mature brain exposed users (p=0.007. No such effect was observed in the frontal cortex. In rats, a significant age-BY-treatment effect (p<0.01 was observed as well, however only in the frontal cortex. CONCLUSIONS: These age-related effects most likely reflect differences in the maturational stage of the 5-HT projection fields at age-at-first exposure and enhanced outgrowth of the 5-HT system due to 5-HT's neurotrophic effects. Ultimately, our findings stress the need for more knowledge on the effects of pharmacotherapies that alter brain 5-HT levels in the pediatric population.

  15. Benzonidazole levels in blood vary with age in rats.

    Science.gov (United States)

    Bulffer, Romina Fernanda; Castro, José Alberto; Fanelli, Silvia Laura

    2011-05-01

    Benznidazole (Bz) exhibits toxic side effects in animal studies and clinical use. Reductive metabolism of Bz in liver microsomes modulates the duration of its chemotherapeutic effect and its toxicity. The rate of this metabolism depends on age and is less intense in newborns and youngsters than in adults. In the present study, we determined Bz blood levels in rats of different ages that received Bz intragastrically (100 mg/kg). We developed and validated a high-pressure liquid chromatography with UV detector method for determination of Bz levels in whole blood. Bz levels were significantly higher and persisted for longer periods of time in the blood of young rats when compared to that of adult animals. PMID:21655830

  16. Benznidazole levels in blood vary with age in rats

    Directory of Open Access Journals (Sweden)

    Romina Fernanda Bulffer

    2011-05-01

    Full Text Available Benznidazole (Bz exhibits toxic side effects in animal studies and clinical use. Reductive metabolism of Bz in liver microsomes modulates the duration of its chemotherapeutic effect and its toxicity. The rate of this metabolism depends on age and is less intense in newborns and youngsters than in adults. In the present study, we determined Bz blood levels in rats of different ages that received Bz intragastrically (100 mg/kg. We developed and validated a high-pressure liquid chromatography with UV detector method for determination of Bz levels in whole blood. Bz levels were significantly higher and persisted for longer periods of time in the blood of young rats when compared to that of adult animals.

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

    International Nuclear Information System (INIS)

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

  18. Using laser confocal scanning microscope to study ischemia-hypoxia injury in rat brain slice

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The level of lipid peroxidation and cellular necrosis in rat living brain slices during brain ischemia-hypoxia injury have been observed using a laser confocal scanning microscope (LCSM) with double labeling of fluorescent probes D-399 (2,7-dichlorofluorescin diacetate) and propidium iodide (PI).The hypoxia and/or reoxygenation injury in rat brain slices is markedly decreased by pretreatment with L-NG-nitro-arginine (L-NNA) and N-acetylcysteine (NAC),showing that the nitric oxide (NO) and other free radicals play an important role in brain ischemia-hypoxia injury.

  19. Generation of primary cultures of bovine brain endothelial cells and setup of cocultures with rat astrocytes

    DEFF Research Database (Denmark)

    Helms, Hans C; Brodin, Birger

    2014-01-01

    In vitro models of the blood-brain barrier are useful tools to study blood-brain barrier function as well as drug permeation from the systemic circulation to the brain parenchyma. However, a large number of the available in vitro models fail to reflect the tightness of the in vivo blood-brain...... barrier. The present protocol describes the setup of an in vitro coculture model based on primary cultures of endothelial cells from bovine brain microvessels and primary cultures of rat astrocytes. The model displays a high electrical tightness and expresses blood-brain barrier marker proteins....

  20. Aging and iron accumulation in the monkey brain

    International Nuclear Information System (INIS)

    Iron is deposited in the mammalian brain with a characteristic distribution, its amount increasing with aging. The relative abundance of iron in the globus pallidus, substantia nigra and putamen is thought to be responsible for the hypointensity of these nuclei on T2-weighted MR images, due to magnetic susceptibility effects. However, no quantitative correlation between iron content and hypointensity has been made to confirm this hypothesis. Two young (1-year-old) and two older (18-year-old) rhesus monkeys were studied with MR imaging at different field strengths (0.5, 1.5, 2.0 T). MR signal intensities from different anatomic structures were measured on T2-weighted coronal images (2,6000/80 [repetition time msec/echo time msec]). At completion of the MR studies, the monkeys were killed, coronal brain sections were stained for iron (Perls method), and optical densities of anatomic structures were measured. A quantitative correlation between the iron content and the signal intensity decrease was found on T2-weighted images in both deep and superficial cerebral structures. The detectability of magnetic susceptibility effects in a single structure is determined by the amount of iron present, with the threshold being inversely correlated to the strength of the magnetic field

  1. Daicong solution effects on brain ultrastructure in a rat model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Qian Yue; Yuling Ding; Hongyan Wang; Shumei Zhao; Shengming Zhang; Hongjuan Wu; Yiguang Wang; Fengjie Li; Yuanyuan Yang; Juanjuan Liu

    2008-01-01

    BACKGROUND: Infusion of kainic acid into the basal nuclei induces neuronal excitotoxicity, degeneration, and necrosis, resulting in disturbed learning and memory functions.OBJECTIVE: To explore the effects of different doses of traditional Chinese medicine Daicong solution on brain ultrastructure in a rat model of Alzheimer's disease.DESIGN, TIME AND SETTING: The randomized, controlled, cellular morphology experiment was performed at the Shandong Provincial Key Laboratory of Molecular Immunology of Weifang Medical University, China from October 2006 to March 2007.MATERIALS: Fifty healthy, Sprague Dawley rats, aged 22-months, were used to establish rat models of Alzheimer's disease. The Morris water maze was prepared at the Pharmacometrics Key Laboratory of Weifang Medical University in Shandong Province of China. Traditional Chinese medicine Daicong solution (crude drug 1 g/mL), composed of radix ginseng, rehmannia dried rhizome, anemarrhenae and radix astragali, was produced by the Department of Pharmacy of Hospital Affiliated to Weifang Medical University. Kainic acid was provided by Professor Xiuyan Li from Weifang Medical University.METHODS: A total of 40 model rats were equally and randomly divided into four groups: dementia model, low-dose Daicong solution (5 g/kg/d), moderate-dose Daicong solution (10 g/kg/d), and high-dose Daicong solution (20 g/kg/d). An additional 10 healthy rats served as the normal control group. Rats in the dementia model and normal control groups received saline (10 mL/kg/d).MAIN OUTCOME MEASURES: Neural cell ultrastructure was observed utilizing electron microscopy after 1 month of respective treatments.RESULTS: Compared with the normal control group, electron density and the number of ribosomes were significantly reduced in neuronal cytoplasm, and many lipofuscin grains and vacuole-like changes were observed in mitochondria in the dementia model group. In addition, nuclear chromatin presented with different sizes of plaque

  2. Beneficial influence of physical exercise following status epilepticus in the immature brain of rats.

    Science.gov (United States)

    Gomes, F G Novaes; Gomes Da Silva, S; Cavalheiro, E A; Arida, R M

    2014-08-22

    Studies in adult animals have demonstrated a beneficial effect of physical exercise on epileptic insults. Although the effects of physical exercise on the mature nervous system are well documented, its influence on the developing nervous system subjected to injuries in childhood has been little explored. The purpose of our study was to investigate whether a physical exercise program applied during brain development could influence the hippocampal plasticity of rats submitted to status epilepticus (SE) induced by pilocarpine model at two different ages of the postnatal period. Male Wistar rats aged 18 (P18) and 28 (P28) days were randomly divided into four groups: Control (CTRL), Exercise (EX), SE (SE) and SE Exercise (SE/EX) (n=17 per group). After the aerobic exercise program, histological and behavioral (water maze) analyses were performed. Our results showed that only animals subjected to pilocarpine-induced SE at P28 presented spontaneous seizures during the observational period. A significant reduction in seizure frequency was observed in the SE/EX group compared to the SE group. In adulthood, animals submitted to early-life SE displayed impairment in long-term memory in the water maze task, while the exercise program reversed this deficit. Reduced mossy fiber sprouting in the dentate gyrus was noted in animals that presented spontaneous seizures (SE/EX vs SE). Exercise increased cell proliferation (Ki-67 staining) and anti-apoptotic response (bcl-2 staining) and reduced pro-apoptotic response (Bax staining) in animals of both ages of SE induction (P18/28). Exercise also modified the brain-derived neurotrophic factor (BDNF) levels in EX and SE/EX animals. Our findings indicate that in animals subjected to SE in the postnatal period a physical exercise program brings about beneficial effects on seizure frequency and hippocampal plasticity in later stages of life. PMID:24857853

  3. The effects of baicalin on inhibiting brain aging, glycation-oxidative stress and insulin resistance in D-galactose-induced aging rats%黄芩苷对D半乳糖诱导衰老大鼠拮抗脑老化糖基化氧化应激及胰岛素抵抗作用

    Institute of Scientific and Technical Information of China (English)

    钟成; 潘竞锵; 吕俊华; 郑琳颖; 李博萍

    2012-01-01

    models were randomly divide into 5groups ( 15 rats for each goup ):model control,metformin ( Met,150 mg·kg-1 ),and pimagedine ( PG,150 mg·kg-1 ),Bai high dose group( 300 mg·kg-1 )and low dose group ( 150 mg·kg-1 ); then ip D-gal and different drugs or distilled water ip-treated qd for 42 days.In the end of the experiment,the contents of fasting blood glucose ( FBG ),fruetosamine ( FRA ),glycosylated hemoglobin ( HbAIc ),advanced glycation end-products ( AGEs ),insulin,and malondialdehyde ( MDA ) were analyzed,the activity of aldose reductase ( AR ) and superoxide dismutase ( SOD ) were determined,insulin sensitivity index ( ISI ) was counted and spatial seeking ability by Morris water maze test was selected.Results As compared with blank control,the concentration of FBG,FRA,HbA lc,AGEs,insulin and MDA increased ( P< 0.01 ),SOD activity declined ( P< 0.01 ),AR activity enhanced ( P< 0.01 ),ISI reduced ( P< 0.01 ),and spatial seeking ability significantly declined in the D-gat-induced rats; as compared with the D-gal-induced aging rats,the contents of FBG,FRA,HbAIc,AGEs and insulin were reduced,AR activity was inhibited,SOD activity was elevated,and spatial seeking ability was significantly increased by using Met,PG,and Bai at high or low dose ( P < 0.05 or P < 0.01 ).Conclusions Baicalin can antagonize insulin resistance,improve insulin sensitivity,inhibit formation of glycation products-oxidative stress and activity of rate-limiting enzyme AR in polyoi pathway,suppress inflamnatory reaction,and improve spatial seeking ability in D-gal-induced aging rats.The effects of baicalin reveals a dose-effect relationship.

  4. A Brain-Wide Study of Age-Related Changes in Functional Connectivity

    NARCIS (Netherlands)

    Geerligs, Linda; Renken, Remco J.; Saliasi, Emi; Maurits, Natasha M.; Lorist, Monicque M.

    2015-01-01

    Aging affects functional connectivity between brain areas, however, a complete picture of how aging affects integration of information within and between functional networks is missing. We used complex network measures, derived from a brain-wide graph, to provide a comprehensive overview of age-rela

  5. Peripheral Levels of AGEs and Astrocyte Alterations in the Hippocampus of STZ-Diabetic Rats.

    Science.gov (United States)

    Nardin, Patrícia; Zanotto, Caroline; Hansen, Fernanda; Batassini, Cristiane; Gasparin, Manuela Sangalli; Sesterheim, Patrícia; Gonçalves, Carlos-Alberto

    2016-08-01

    Diabetic patients and streptozotocin (STZ)-induced diabetes mellitus (DM) models exhibit signals of brain dysfunction, evidenced by neuronal damage and memory impairment. Astrocytes surrounding capillaries and synapses modulate many brain activities that are connected to neuronal function, such as nutrient flux and glutamatergic neurotransmission. As such, cognitive changes observed in diabetic patients and experimental models could be related to astroglial alterations. Herein, we investigate specific astrocyte changes in the rat hippocampus in a model of DM induced by STZ, particularly looking at glial fibrillary acidic protein (GFAP), S100B protein and glutamate uptake, as well as the content of advanced glycated end products (AGEs) in serum and cerebrospinal fluid (CSF), as a consequence of elevated hyperglycemia and the content of receptor for AGEs in the hippocampus. We found clear peripheral alterations, including hyperglycemia, low levels of proinsulin C-peptide, elevated levels of AGEs in serum and CSF, as well as an increase in RAGE in hippocampal tissue. We found specific astroglial abnormalities in this brain region, such as reduced S100B content, reduced glutamate uptake and increased S100B secretion, which were not accompanied by changes in GFAP. We also observed an increase in the glucose transporter, GLUT-1. All these changes may result from RAGE-induced inflammation; these astroglial alterations together with the reduced content of GluN1, a subunit of the NMDA receptor, in the hippocampus may be associated with the impairment of glutamatergic communication in diabetic rats. These findings contribute to understanding the cognitive deficits in diabetic patients and experimental models. PMID:27084774

  6. EFFECTS OF HYPERTHERMIA AND HYPERTHERMIA PLUS MICROWAVES ON RAT BRAIN ENERGY METABOLISM

    Science.gov (United States)

    The effects of hyperthermia, alone and in conjunction with microwave exposure, on brain energetics were studied in anesthetized male Sprague-Dawley rats. The effects of temperature on adenosine triphosphate concentration (ATP) and creatine phosphate concentration (CP) was determi...

  7. Tumor necrosis factor α antibody prevents brain damage of rats with acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yan-Ling Yang; Ji-Peng Li; Kai-Zong Li; Ke-Feng Dou

    2004-01-01

    AIM: To study the protective effects of tumor necrosis factor á (TNFα) antibody on pancreatic encephalopathy in rats.METHODS:One hundred and twenty SD rats were randomly divided into normal control group,acute necrotizing pancreatitis group and TNFα antibody treated group.Acute hemorrhage necrotizing pancreatitis model in rats was induced by retrograde injection of 50 g/L sodium taurocholate into the pancreatobiliary duct.Serum TNFα was detected and animals were killed 12 h after drug administration.Changes in content of brain water,MDA and SOD as well as leucocyte adhesion of brain microvessels were measured.RESULTS:In TNFα antibody treated group,serum TNFálevel was decreased.Content of brain water,MDA and SOD as well as leucocyte adhesion were decreased significantly in comparison with those of acute necrotizing pancreatitis group (P<0.05).CONCLUSION:TNFα antibody can alleviate the brain damage of rats with acute hemorrhage necrotizing pancreatitis.

  8. Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

    Directory of Open Access Journals (Sweden)

    Giuliani Patricia

    2010-02-01

    Full Text Available Abstract Background Both hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia. In the present study, quantitative proton magnetic resonance spectroscopy was used to evaluate regional metabolic alterations, following a 24-hour hypoxic or hyperoxic exposure on the background of ischemic brain insult, in two contrasting age-groups of rats: young - 3 months old and aged - 24 months old. Methods Cerebral ischemia was induced by ligation of the right common carotid artery. Concentrations of eight metabolites (alanine, choline-containing compounds, total creatine, γ-aminobutyric acid, glutamate, lactate, myo-inositol and N-acetylaspartate were quantified from extracts in three different brain regions (fronto-parietal and occipital cortices and the hippocampus from both hemispheres. Results In the control normoxic condition, there were significant increases in lactate and myo-inositol concentrations in the hippocampus of the aged rats, compared with the respective values in the young ones. In the ischemia-hypoxia condition, the most prevalent changes in the brain metabolites were found in the hippocampal regions of both young and aged rats; but the effects were more evident in the aged animals. The ischemia-hyperoxia procedure caused less dedicated changes in the brain metabolites, which may reflect more limited tissue damage. Conclusions We conclude that the hippocampus turns out to be particularly susceptible to hypoxia overlaid on cerebral ischemia and that old age further increases this susceptibility.

  9. The expression of TRPA1 mRNA in the rat brain

    Institute of Scientific and Technical Information of China (English)

    Peng Du; Shua Li; Jinyu Zheng; Zhi-yuan Yu; Minjie Xie; Wei Wang

    2006-01-01

    Objective: To investigate the distribution of TRPA1 (one kind of the TRP-like ion channel family) channel in the hippocampus and cerebral cortex of rat. Methods: RT-PCR was used to amplify the fragment of TRPA1 in the DRG (dorsal root ganglion), hippocampus and cerebral cortex of adult SD rat. In situ hybridization staining was used to show the distribution of TRPA1 mRNA in the hippocampus and cerebral cortex of adult rat brain. Results: Both RT-PCR and in situ hybridization staining showed that TRPA1 mRNA was expressed in hippocampus and cerebral cortex of the adult rat brain. Conclusion: Ourresults suggest that there is expression of TRPA1 mRNA both in the hippocampus and cerebral cortex of the adult rat brain.

  10. Effects of Chronic Renal Failure on Brain Cytochrome P450 in Rats.

    Science.gov (United States)

    Naud, Judith; Harding, Jessica; Lamarche, Caroline; Beauchemin, Stephanie; Leblond, Francois A; Pichette, Vincent

    2016-08-01

    Chronic renal failure (CRF) impedes renal excretion of drugs and their metabolism by reducing the expression of liver cytochrome P450 (P450). Uremic serum contains factors, such as parathyroid hormone (PTH), that decrease liver P450s. The P450s are also involved in the metabolism of xenobiotics in the brain. This study investigates: 1) the effects of CRF on rat brain P450, 2) the role of PTH in the downregulation of brain P450s in CRF rats, and 3) the effects of PTH on P450s in astrocytes. Protein and mRNA expression of P450s were assessed in the brain of CRF and control (CTL) rats, as well as from CTL or CRF rats that underwent parathyroidectomy (PTX) 1 week before nephrectomy. CYP3A activity was measured using 3-[(3, 4-difluorobenzyl) oxy]-5, 5-dimethyl-4-[4-methylsulfonyl) phenyl] furan-2(5H)-1 metabolism in brain microsomal preparation. CYP3A protein expression was assessed in primary cultured astrocytes incubated with serum obtained from CRF or CTL rats or with PTH. Significant downregulations (≥40%) of CYP1A, CYP2C11, and CYP3A proteins were observed in microsomes from CRF rat brains. CYP3A activity reduction was also observed. CYP3A expression and activity were unaffected in PTX-pretreated CRF rats. Serum of PTX-treated CRF rats had no impact on CYP3A levels in astrocytes compared with that of untreated CRF rats. Finally, PTH addition to normal calf serum induced a reduction in CYP3A protein similar to CRF serum, suggesting that CRF-induced hyperparathyroidism is associated with a significant decrease in P450 drug-metabolizing enzymes in the brain, which may have implications in drug response. PMID:27271372

  11. High-sensitivity phase-contrast tomography of rat brain in phosphate buffered saline

    OpenAIRE

    Pfeiffer, F.; David, C.; Bunk, O.; Poitry-Yamate, C.; Grütter, R; B. Müller; Weitkamp, T.

    2009-01-01

    We report advances and complementary results concerning a recently developed method for high-sensitivity grating-based x-ray phase-contrast tomography. In particular we demonstrate how the soft tissue sensitivity of the technique can be used to obtain in-vitro tomographic images of rat brain specimens. Contrary to our previous experiments with fixated specimen (chemically modified or formalin fixed), the present results on the rat's brain are closer to the in-vivo situation. The findings are ...

  12. Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain

    OpenAIRE

    Xiao, DaLiao; Zhang, Lubo

    2008-01-01

    Cocaine abuse during pregnancy has been associated with numerous adverse perinatal outcomes. Aims: The present study was to determine whether prenatal cocaine exposure induced apoptosis and the possible role of Bcl-2 family genes in the programming cell death in fetal rat brain. Main methods: Pregnant rats were treated with cocaine subcutaneously (30 & 60 mg/kg/day) from day 15 to 21 of gestation. Then the fetal and maternal brains were isolated. Key findings: Cocaine produced a dose-dependen...

  13. Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain

    OpenAIRE

    DaLiao Xiao, Lubo Zhang

    2008-01-01

    Cocaine abuse during pregnancy has been associated with numerous adverse perinatal outcomes. Aims: The present study was to determine whether prenatal cocaine exposure induced apoptosis and the possible role of Bcl-2 family genes in the programming cell death in fetal rat brain. Main methods: Pregnant rats were treated with cocaine subcutaneously (30 & 60 mg/kg/day) from day 15 to 21 of gestation. Then the fetal and maternal brains were isolated. Key findings: Cocaine produced a dose-depe...

  14. Pulpal responses to cavity preparation in aged rat molars.

    Science.gov (United States)

    Kawagishi, Eriko; Nakakura-Ohshima, Kuniko; Nomura, Shuichi; Ohshima, Hayato

    2006-10-01

    The dentin-pulp complex is capable of repair after tooth injuries including dental procedures. However, few data are available concerning aged changes in pulpal reactions to such injuries. The present study aimed to clarify the capability of defense in aged pulp by investigating the responses of odontoblasts and cells positive for class II major histocompatibility complex (MHC) to cavity preparation in aged rat molars (300-360 days) and by comparing the results with those in young adult rats (100 days). In untreated control teeth, immunoreactivity for intense heat-shock protein (HSP)-25 and nestin was found in odontoblasts, whereas class-II-MHC-positive cells were densely distributed in the periphery of the pulp. Cavity preparation caused two types of pulpal reactions based on the different extent of damage in the aged rats. In the case of severe damage, destruction of the odontoblast layer was conspicuous at the affected site. By 12 h after cavity preparation, numerous class-II-MHC-positive cells appeared along the pulp-dentin border but subsequently disappeared together with HSP-25-immunopositive cells, and finally newly differentiated odontoblast-like cells took the place of the degenerated odontoblasts and acquired immunoreactivity for HSP-25 and nestin by postoperative day 3. In the case of mild damage, no remarkable changes occurred in odontoblasts after operation, and some survived through the experimental stages. These findings indicate that aged pulp tissue still possesses a defense capacity, and that a variety of reactions can occur depending on the difference in the status of dentinal tubules and/or odontoblast processes in individuals.

  15. Increased expression of aquaporin-4 in brain tissue of amygdala-kindled rats

    Institute of Scientific and Technical Information of China (English)

    Yinghui Chen; Yongbo Zhao

    2011-01-01

    Recurrent epileptic seizures can lead to brain edema, indicating that water regulation may be perturbed by seizures.We hypothesized that the expression of the brain water channel aquaporin-4 (AQP-4) may be upregulated in the epileptic brain.In the present study, we established the amygdala kindling model of epilepsy, and quantified AQP-4 protein and mRNA levels, using reverse transcription-PCR, immunohistochemistry and western blotting, in epileptic and control rats.We found that AQP-4 was overexpressed in the cerebral cortex of rats with epilepsy compared with controls.These findings show that AQP-4 is highly expressed in the brain of amygdala-kindled rats, suggesting that repeated seizures affect water homeostasis in the brain.

  16. Effects of morphine dependence and withdrawal on levels of neurosteroids in rat brain

    Institute of Scientific and Technical Information of China (English)

    Cai-zhen YAN; Yan-ning HOU

    2004-01-01

    AIM: To investigate the effects of morphine dependence and withdrawal on the concentrations of neurosteroids in rat brain. METHODS: A method of simultaneous quantification of neurosteroids by gas chromatography-mass spectrometry (GC-MS) had been established. RESULTS: The chronic morphine administration (ip) resulted in a marked decrease in the brain concentrations of pregnenolone (PREG), progesterone (PROG), and pregenenolone sulfate (PREGS) in rats killed 6 h after the last treatment. In contrast, there were no significant effects of morphine dependence on the brain concentrations of allopregnanolone (AP), dihydroepiandrosterone (DHEA), and dihydroepiandrosterone sulfate (DHEAS). Naloxone-induced withdrawal produced a significant increase in the concentrations of PREG, PROG, AP, DHEA, PREGS, and DHEAS as compared with the control group.CONCLUSION: Morphine dependence and withdrawal affected the concentrations of neurosteroids in rat brain,which suggests that endogenous neurosteroids in brain might be related to the development of morphine dependence and withdrawal.

  17. Elevated RhoA/Rho-kinase activity in the aged rat penis: mechanism for age-associated erectile dysfunction.

    Science.gov (United States)

    Jin, Liming; Liu, Tongyun; Lagoda, Gwen A; Champion, Hunter C; Bivalacqua, Trinity J; Burnett, Arthur L

    2006-03-01

    Epidemiologic studies have shown that aging accounts significantly for the prevalence of erectile dysfunction (ED). The pathophysiology of ED during aging and its underlying molecular mechanisms are largely unknown. We hypothesized that increased RhoA/Rho-kinase signaling is a major factor in the pathogenesis of age-associated ED and the mechanism involves increased penile smooth muscle contractility through inhibition of myosin light chain phosphatase. Male Fischer 344 young (4 month old) and aged (20-22 month old) rats underwent erectile function testing in vivo by measuring intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) upon electrical stimulation of the cavernous nerve. The data demonstrated that erectile function was significantly lower in aged rats than that in young rats at all voltages tested (Ppenes by 95 +/- 15 and 56 +/- 8% (Ppenes of aged and young rats for 7 days markedly improved erectile function in aged rats when compared with that in young rats (Ppenes receiving AAV vehicle treatment was twofold greater than that in young rat penes receiving AAV vehicle treatment, while it was reduced to a level similar to that in young rat penes after gene therapy of T19NRhoA (P<0.05). Taken together, these data suggest that impaired erectile function during the aging process involves increased RhoA/Rho-kinase signaling, and this pathway may be exploited for the treatment of age-associated ED. PMID:16396994

  18. Age-related changes of normal adult brain structure: analysed with diffusion tensor imaging

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yun-ting; ZHANG Chun-yan; ZHANG Jing; LI Wei

    2005-01-01

    Background It is known that the brain structure changes with normal aging. The objective of this study was to quantify the anisotropy and average diffusion coefficient (DCavg) of the brain in normal adults to demonstrate the microstructure changes of brain with aging.Methods One hundred and six normal adults were examined with diffusion tensor imaging (DTI). The fractional anisotropy (FA), 1-volume ratio (1-VR), relative anisotropy (RA) and average diffusion coefficient (DCavg) of different anatomic sites of brain were measured, correlated with age and compared among three broad age groups.Results Except in lentiform nucleus, the anisotropy increased and DCavg decreased with aging. Both anisotropy and DCavg of lentiform nucleus increased with aging. The normal reference values of DTI parameters of normal Chinese adult in major anatomic sites were acquired. Conclusions DTI data obtained noninvasively can reflect the microstructural changes with aging. The normal reference values acquired can serve as reference standards in differentiation of brain white matter diseases.

  19. Through metal binding, curcumin protects against lead- and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain.

    Science.gov (United States)

    Daniel, Sheril; Limson, Janice L; Dairam, Amichand; Watkins, Gareth M; Daya, Santy

    2004-02-01

    Curcumin, the major constituent of turmeric is a known, naturally occurring antioxidant. The present study examined the ability of this compound to protect against lead-induced damage to hippocampal cells of male Wistar rats, as well as lipid peroxidation induced by lead and cadmium in rat brain homogenate. The thiobarbituric assay (TBA) was used to measure the extent of lipid peroxidation induced by lead and cadmium in rat brain homogenate. The results show that curcumin significantly protects against lipid peroxidation induced by both these toxic metals. Coronal brain sections of rats injected intraperitoneally with lead acetate (20 mg/kg) in the presence and absence of curcumin (30 mg/kg) were compared microscopically to determine the extent of lead-induced damage to the cells in the hippocampal CA1 and CA3 regions, and to establish the capacity of curcumin to prevent such damage. Lead-induced damage to the neurons was significantly curtailed in the rats injected with curcumin. Possible chelation of lead and cadmium by curcumin as its mechanism of neuroprotection against such heavy metal insult to the brain was investigated using electrochemical, ultraviolet spectrophotometric and infrared spectroscopic analyses. The results of the study show that there is an interaction between curcumin and both cadmium and lead, with the possible formation of a complex between the metal and this ligand. These results imply that curcumin could be used therapeutically to chelate these toxic metals, thus potentially reducing their neurotoxicity and tissue damage.

  20. Hyperammonemia,brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paravrtamol intoxication

    Institute of Scientific and Technical Information of China (English)

    Camila Scorticati; Juan P. Prestifilippo; Francisco X. Eizayaga; José L. Castro; Salvador Romay; Maria A. Fernández; Abraham Lemberg; Juan C. Perazzo

    2004-01-01

    AIM: To study the blood-brain barrier integrity, brain edema,animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication.METHODS: Adults male Wistar rats were divided into four groups. Group Ⅰ: sham operation; Ⅱ: Prehepatic portal hypertension, produced by partial portal vein ligation; Ⅲ:Acetaminophen intoxication and Ⅳ: Prehepatic portal hypertension plus acetaminophen. Acetaminophen was administered to produce acute hepatic injury. Portal pressure, liver serum enzymes and ammonia plasma levels were determined. Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity. Reflexes and behavioral tests were recorded.RESULTS: Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ. Liver enzymes and ammonia plasma levels were increased in groups Ⅱ, Ⅳ and Ⅳ. Prehepatic portal hypertension (group Ⅱ), acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia. Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ. Behavioral test (rota rod) was altered in group Ⅳ.CONCLUSION: These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (cytotoxic). Group Ⅳ, with behavioral altered test, can be considered as a model for study at an early stage of portal-systemic encephalopathy.

  1. Expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats, and to observe the temporal patterns of its expressions following percussion.METHODS: Male Sprague-Dawley rats were divided into normal control, sham operation control and injury groups. The rats of injury group subjected to moderate lateral fluid percussion injury (0.2 mPa), and then were subdivided into 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h and 12 h groups according to the time elapsed after injury. The expression of c-jun was studied by immunohistochemistry and in situ hybridization. RESULTS: After percussion for 15 min, Jun positive neurons increased in brain stem progressively, and peaked at 12h. At 5min after percussion, the induction of c-jun mRNA was increased, and remained elevated up to 1h-2h after brain injury. CONCLUSION: The induction and expression of the c-jun in brain stem after fluid percussion brain injury were increased rapidly and lasted for a long time.

  2. Effect of MCI-186 on ischemia-induced changes in monoamine metabolism in rat brain.

    Science.gov (United States)

    Oishi, R; Itoh, Y; Nishibori, M; Watanabe, T; Nishi, H; Saeki, K

    1989-11-01

    We examined the effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a novel free radical scavenger and an inhibitor of ischemia-induced brain edema, on monoamine metabolism in the brains of both normal and ischemic rats. In normal rats, 3 mg/kg i.v. MCI-186, a dose that prevents ischemic brain edema, had no significant effect on brain concentrations of dopamine, norepinephrine, 5-hydroxytryptamine, or their metabolites. After the injection of 5 microliters of 3% polyvinyl acetate into the left internal carotid artery, concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid markedly increased, but that of norepinephrine decreased, in the left telencephalon of embolized rats compared with control rats injected with vehicle; the concentration of 5-hydroxyindoleacetic acid also increased slightly. These effects were maximal 2 hours after embolization. The turnover rate of dopamine between 6 and 8 hours after embolization was significantly higher but that of norepinephrine was slightly lower than that in vehicle-treated rats. When rats were treated with 3 mg/kg i.v. MCI-186 immediately after the injection of polyvinyl acetate, the embolization-induced changes in monoamine metabolism were less marked. Our results suggest that MCI-186 attenuates ischemia-induced changes in brain monoamine metabolism, probably due to its free radical scavenging action, although it has no marked effect in normal rats. PMID:2815191

  3. The Effect of Aging on Resting-State Brain Function: An fMRI Study

    Directory of Open Access Journals (Sweden)

    A. H. Batouli

    2009-11-01

    Full Text Available Background/Objective: Healthy aging may be accompanied by some types of cognitive impairment; moreover, normal aging may cause natural atrophy in the healthy human brain. The hypothesis of the healthy aging brain is the structural changes together with the functional impairment happening. The brain struggles to over-compensate for those functional age-related impairments to continue as a healthy brain in its functions. Our goal in this study was to evaluate the effects of aging on the resting-state activation network of the brain using the multi-session probabilistic independent component analysis algorithm (PICA. "nPatients and Methods: We compared the resting-state brain activities between two groups of healthy aged and young subjects, so we examined 30 right-handed subjects and finally 12 healthy aging and 11 controls were enrolled in the study. "nResults: Our results showed that during the resting-state, older brains benefit from larger areas of activation, while in young competent brains, higher activation occurs in terms of greater intensity. These results were obtained in prefrontal areas as regions with regard to memory function as well as the posterior cingulate cortex (PCC as parts of the default mode network. Meanwhile, we reached the same results after normalization of activation size with total brain volume. "nConclusion: The difference in activation patterns between the two groups shows the brain's endeavor to compensate the functional impairment.

  4. Sexual differentiation of the brain and partner preference in the male rat

    NARCIS (Netherlands)

    J. Bakker (Julie)

    1996-01-01

    textabstractThe studies reported in this thesis have been conducted to investigate the sexual differentiation of partner preference in the male rat. Initially, the effects of neonatal inhibition of brain estrogen formation on later coital behavior and partner preference of the male rat were studied.

  5. Comparative proteomics of rat brain in the BCNU-induced model of cortical dysplasia

    Institute of Scientific and Technical Information of China (English)

    郭谊

    2014-01-01

    Objective To screen the differential proteins in the brain(neocortex and hippocampus)between the rats with cortical dysplasia(CD)and control ones,and investigate the role of their alteration in the development of epilepsy in CD.Methods Cortical dysplasia was induced in rat pups via in utero delivery of BCNU.A two-dimensional electrophoresis

  6. Pimonidazole binding in C6 rat brain glioma: relation with lipid droplet detection.

    NARCIS (Netherlands)

    Zoula, S.; Rijken, P.F.J.W.; Peters, J.P.W.; Farion, R.; Sanden, B.P.J. van den; Kogel, A.J. van der; Decorps, M.; Remy, C.

    2003-01-01

    In C6 rat brain glioma, we have investigated the relation between hypoxia and the presence of lipid droplets in the cytoplasm of viable cells adjacent to necrosis. For this purpose, rats were stereotaxically implanted with C6 cells. Experiments were carried out by the end of the tumour development.

  7. The metabolism of malate by cultured rat brain astrocytes

    International Nuclear Information System (INIS)

    Since malate is known to play an important role in a variety of functions in the brain including energy metabolism, the transfer of reducing equivalents and possibly metabolic trafficking between different cell types; a series of biochemical determinations were initiated to evaluate the rate of 14CO2 production from L-[U-14C]malate in rat brain astrocytes. The 14CO2 production from labeled malate was almost totally suppressed by the metabolic inhibitors rotenone and antimycin A suggesting that most of malate metabolism was coupled to the electron transport system. A double reciprocal plot of the 14CO2 production from the metabolism of labeled malate revealed biphasic kinetics with two apparent Km and Vmax values suggesting the presence of more than one mechanism of malate metabolism in these cells. Subsequent experiments were carried out using 0.01 mM and 0.5 mM malate to determine whether the addition of effectors would differentially alter the metabolism of high and low concentrations of malate. Effectors studied included compounds which could be endogenous regulators of malate metabolism and metabolic inhibitors which would provide information regarding the mechanisms regulating malate metabolism. Both lactate and aspartate decreased 14CO2 production from malate equally. However, a number of effectors were identified which selectively altered the metabolism of 0.01 mM malate including aminooxyacetate, furosemide, N-acetylaspartate, oxaloacetate, pyruvate and glucose, but had little or no effect on the metabolism of 0.5 mM malate. In addition, alpha-ketoglutarate and succinate decreased 14CO2 production from 0.01 mM malate much more than from 0.5 mM malate. In contrast, a number of effectors altered the metabolism of 0.5 mM malate more than 0.01 mM. These included methionine sulfoximine, glutamate, malonate, alpha-cyano-4-hydroxycinnamate and ouabain

  8. The effects of trypsin on rat brain astrocyte activation.

    Directory of Open Access Journals (Sweden)

    Masoud Fereidoni

    2013-12-01

    Full Text Available Astrocytes are cells within the central nervous system which are activated in a wide spectrum of infections, and autoimmune and neurodegenerative diseases. In pathologic states, they produce inflammatory cytokines, chemokines, and nitric oxide (NO, and sometimes they induce apoptosis. Their protease-activated receptors (PARs can be activated by proteases, e.g. thrombin and trypsin, which are important in brain inflammation. The current study aimed to investigate the effects of different concentrations of trypsin (1 to 100U/ml on cultured astrocytes.In the present study, two-day rat infants' brains were isolated and homogenized after meninges removal, then cultivated in DMEM + 10% FBS medium. 10 days later, astrocytes were harvested and recultivated for more purification (up to 95%, using Immunocytochemistry method, in order to be employed for tests. They were affected by different concentrations of trypsin (1, 5, 10, 15, 20, 40, 60, 80, and 100 U/ml. To reveal the inflammation progress, NO concentrations (the Griess test were assessed after 24 and 48 hours.The results showed that trypsin concentration up to 20 U/ml caused a significant increase in NO, in a dose-dependent manner, on cultured astrocytes (P < 0.001. Trypsin 20 U/ml increased NO production fivefold the control group (P < 0.001. At higher concentrations than 20 U/ml, NO production diminished (P < 0.001. At 100 U/ml, NO production was less than the control group (P < 0.001.Inflammatory effects of trypsin 5-20 U/ml are probably due to the stimulation of astrocytes' PAR-2 receptors and the increasing of the activation of NF-κB, PKC, MAPKs. Stimulation of astrocytes' PAR-2 receptors causes an increase in iNOS activation which in turn leads to NO production. However, higher trypsin concentration possibly made astrocyte apoptosis; therefore, NO production diminished. These assumptions need to be further investigated.

  9. Brain catecholamines in spontaneously hypertensive and DOCA-salt hypertensive rats.

    OpenAIRE

    Fujino, Kazuyuki

    1984-01-01

    The concentrations and alpha-methyl-p-tyrosine (alpha-MPT) induced disappearance of catecholamines, adrenaline, noradrenaline and dopamine, were measured in selected areas of the brainstem and hypothalamus of spontaneously hypertensive rats (SHR) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The catecholamine levels were measured by a sensitive radioenzymatic assay method combined with microdissection of the rat brain. The adrenaline concentration was higher in the area A1 of...

  10. 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.

  11. Disruption of the blood-brain interface in neonatal rat neocortex induces a transient expression of metallothionein in reactive astrocytes

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T

    1995-01-01

    Exposure of the adult rat brain parenchyma to zinc induces an increase in the intracerebral expression of the metal-binding protein, metallothionein, which is normally confined to astrocytes, ependymal cells, choroid plexus epithelial cells, and brain endothelial cells. Metallothionein is express...... induces a transient expression of metallothionein in reactive astrocytes, probably as a response to metals released from the site of the brain injury.......Exposure of the adult rat brain parenchyma to zinc induces an increase in the intracerebral expression of the metal-binding protein, metallothionein, which is normally confined to astrocytes, ependymal cells, choroid plexus epithelial cells, and brain endothelial cells. Metallothionein is expressed...... only in diminutive amounts in astrocytes of the neonatal rat brain, which could imply that neonatal rats are devoid of the capacity to detoxify free metals released from a brain wound. In order to examine the influence of a brain injury on the expression of metallothionein in the neonatal brain, PO...

  12. Effects of ageing and experimental diabetes on insulin-degrading enzyme expression in male rat tissues.

    Science.gov (United States)

    Kochkina, Ekaterina G; Plesneva, Svetlana A; Vasilev, Dmitrii S; Zhuravin, Igor A; Turner, Anthony J; Nalivaeva, Natalia N

    2015-08-01

    Due to an increasing life expectancy in developing countries, cases of type 2 diabetes and Alzheimer's disease (AD) in the elderly are growing exponentially. Despite a causative link between diabetes and AD, general molecular mechanisms underlying pathogenesis of these disorders are still far from being understood. One of the factors leading to cell death and cognitive impairment characteristic of AD is accumulation in the brain of toxic aggregates of amyloid-β peptide (Aβ). In the normally functioning brain Aβ catabolism is regulated by a cohort of proteolytic enzymes including insulin-degrading enzyme (IDE) and their deficit with ageing can result in Aβ accumulation and increased risk of AD. The aim of this study was a comparative analysis of IDE expression in the brain structures involved in AD, as well as in peripheral organs (the liver and kidney) of rats, during natural ageing and after experimentally-induced diabetes. It was found that ageing is accompanied by a significant decrease of IDE mRNA and protein content in the liver (by 32 and 81%) and brain structures (in the cortex by 58 and 47% and in the striatum by 53 and 68%, respectively). In diabetic animals, IDE protein level was increased in the liver (by 36%) and in the striatum (by 42%) while in the brain cortex and hippocampus it was 20-30% lower than in control animals. No significant IDE protein changes were observed in the kidney of diabetic rats. These data testify that ageing and diabetes are accompanied by a deficit of IDE in the brain structures where accumulation of Aβ was reported in AD patients, which might be one of the factors predisposing to development of the sporadic form of AD in the elderly, and especially in diabetics.

  13. Alteration of water-soluble S-100 protein content in microembolized rat brain.

    Directory of Open Access Journals (Sweden)

    Harada,Yasuhiro

    1982-12-01

    Full Text Available The amount of S-100 protein in rat brain embolized with carbon microspheres decreased in parallel with the development of cerebral edema as judged by water content, recovering to the normal range by 24h after embolization. These results suggest the participation of S-100 protein in the permeability characterisitics of nervous system capillaries known as the blood-brain barrier.

  14. Differences in distribution and regulation of astrocytic aquaporin-4 in human and rat hydrocephalic brain

    DEFF Research Database (Denmark)

    Skjolding, Anders Daehli; Holst, Anders Vedel; Broholm, Helle;

    2013-01-01

    findings to human pathophysiology. This study compares expression of aquaporin-4 in hydrocephalic human brain with human controls and hydrocephalic rat brain. Methods:  Cortical biopsies from patients with chronic hydrocephalus (n=29) were sampled secondary to planned surgical intervention. Aquaporin-4...

  15. The diffusion permeability to water of the rat blood-brain barrier

    DEFF Research Database (Denmark)

    Bolwig, T G; Lassen, N A

    1975-01-01

    The diffusion permeability to water of the rat blood-brain-barrier (BBB) was studied. Preliminary data obtained with the Oldendorf tissue uptake method (Oldendorf 1970) in seizure experiments suggested that the transfer from blood to brain of labelled water is diffusion-limited. More definite...

  16. Effects of dietary lipids on renal function of aged rats

    Directory of Open Access Journals (Sweden)

    Valente Gamba C.

    2001-01-01

    Full Text Available Normal aging is accompanied by renal functional and morphological deterioration and dietetic manipulation has been used to delay this age-related decline. We examined the effects of chronic administration of diets containing 5% lipid-enriched diet (LD, w/w on renal function of rats at different ages. Three types of LD were tested: canola oil, fish oil and butter. Mean systemic tail-cuff blood pressure and glycemia remained within the normal range whatever the age and the diet of the animals. Proteinuria began to rise from the 8th month in the groups ingesting LD, while in the control group it increased significantly (above 10 mg/24 h only after the 10th month. With age, a significant and progressive decline in glomerular filtration rate (GFR and renal plasma flow was observed in the LD groups but after 6 months of lipid supplementation, the decline in these parameters was more marked in the butter and fish oil groups. By the 18th month, the lowest GFR level was observed in the group ingesting the butter diet (2.93 ± 0.22 vs 5.01 ± 0.21 ml min-1 kg-1 in control, P<0.05. Net acid excretion, evaluated in 9- and 18-month-old rats, was stimulated in the fish oil group when compared both to control and to the other two LD groups. These results suggest that even low levels of LD in a chronic nutritional regimen can modify the age-related changes in renal function and that the impact of different types of lipid-supplemented diets on renal function depends on the kind of lipid present in the diet.

  17. Atrial arrhythmia in ageing spontaneously hypertensive rats: unraveling the substrate in hypertension and ageing.

    Directory of Open Access Journals (Sweden)

    Dennis H Lau

    Full Text Available BACKGROUND: Both ageing and hypertension are known risk factors for atrial fibrillation (AF although the pathophysiological contribution or interaction of the individual factors remains poorly understood. Here we aim to delineate the arrhythmogenic atrial substrate in mature spontaneously hypertensive rats (SHR. METHODS: SHR were studied at 12 and 15 months of age (n = 8 per group together with equal numbers of age-matched normotensive Wistar-Kyoto control rats (WKY. Electrophysiologic study was performed on superfused isolated right and left atrial preparations using a custom built high-density multiple-electrode array to determine effective refractory periods (ERP, atrial conduction and atrial arrhythmia inducibility. Tissue specimens were harvested for structural analysis. RESULTS: COMPARED TO WKY CONTROLS, THE SHR DEMONSTRATED: Higher systolic blood pressure (p<0.0001, bi-atrial enlargement (p<0.05, bi-ventricular hypertrophy (p<0.05, lower atrial ERP (p = 0.008, increased atrial conduction heterogeneity (p = 0.001 and increased atrial interstitial fibrosis (p = 0.006 & CD68-positive macrophages infiltration (p<0.0001. These changes resulted in higher atrial arrhythmia inducibility (p = 0.01 and longer induced AF episodes (p = 0.02 in 15-month old SHR. Ageing contributed to incremental bi-atrial hypertrophy (p<0.01 and atrial conduction heterogeneity (p<0.01 without affecting atrial ERP, fibrosis and arrhythmia inducibility. The limited effect of ageing on the atrial substrate may be secondary to the reduction in CD68-positive macrophages. CONCLUSIONS: Significant atrial electrical and structural remodeling is evident in the ageing spontaneously hypertensive rat atria. Concomitant hypertension appears to play a greater pathophysiological role than ageing despite their compounding effect on the atrial substrate. Inflammation is pathophysiologically linked to the pro-fibrotic changes in the hypertensive atria.

  18. Simultaneous MRI and PET imaging of a rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Raylman, Raymond R [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States); Majewski, Stan [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Lemieux, Susan K [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States); Velan, S Sendhil [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States); Kross, Brian [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Popov, Vladimir [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Smith, Mark F [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Weisenberger, Andrew G [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Zorn, Carl [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Marano, Gary D [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States)

    2006-12-21

    Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

  19. 1H homonuclear editing of rat brain using semiselective pulses

    International Nuclear Information System (INIS)

    The authors have used a semiselective Hahn spin-echo sequence of the form (1331)-tau-(2662)-tau-AQ, delivered by a surface coil to obtain high-resolution 1H NMR spectra from the brains of intact dead rats. This sequence gave suppression of the tissue water resonance by a factor of 80,000 when tau = 68 ms. Delivery of a frequency-selective Dante pulse train to the alpha-CH resonance of lactate at 4.11 ppm, simultaneously with the 2662 refocusing pulse, altered the j-modulation in the spin-coupled beta-CH3 protons. Subtraction of this spectrum from one in which the Dante was ineffective gave an edited spectrum containing only the beta-CH3 resonance of lactate at 1.31 ppm. When the position of the Dante was shifted to 3.78 ppm to selectively invert the alpha-CH protons of alanine, an edited spectrum of alanine was obtained

  20. Traumatic brain injury impairs synaptic plasticity in hippocampus in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bao-liang; CHEN Xin; TAN Tao; YANG Zhuo; CARLOS Dayao; JIANG Rong-cai; ZHANG Jian-ning

    2011-01-01

    Background Traumatic brain injury (TBl) often causes cognitive deficits and remote symptomatic epilepsy.Hippocampal regional excitability is associated with the cognitive function. However, little is known about injury-induced neuronal loss and subsequent alterations of hippocampal regional excitability. The present study was designed to determine whether TBl may impair the cellular circuit in the hippocampus.Methods Forty male Wistar rats were randomized into control (n=20) and TBl groups (n=20). Long-term potentiation,extracellular input/output curves, and hippocampal parvalbumin-immunoreactive and cholecystokinin-immunoreactive interneurons were compared between the two groups.Results TBI resulted in a significantly increased excitability in the dentate gyrus (DG), but a significantly decreased excitability in the cornu ammonis 1 (CA1) area. Using design-based stereological injury procedures, we induced interneuronal loss in the DG and CA3 subregions in the hippocampus, but not in the CA1 area.Conclusions TBl leads to the impairment of hippocampus synaptic plasticity due to the changing of interneuronal interaction. The injury-induced disruption of synaptic efficacy within the hippocampal circuit may underlie the observed cognitive deficits and symptomatic epilepsy.

  1. Phospholipase A_2 changes and its significance on brain tissue of rat in severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Multiple systemorgan failure is often compli-cated with SAP and PLA2could play an i mportantrole in the study of brain damages.Through thestudy of makingthe rat SAP model inthis study,thesignificance of PLA2on brain damages was surveyedand reported.Materials and methods1 The rat SAP model and its classificationEighty male Sprague-Dawley rats,weight(300±30)g,were randomly divided into4groups:thecontrol group,the sham-operation group,the SAPgroup and the treat ment group of SAP.The ratswere not given food but...

  2. Astrocytes from adult Wistar rats aged in vitro show changes in glial functions.

    Science.gov (United States)

    Souza, Débora Guerini; Bellaver, Bruna; Raupp, Gustavo Santos; Souza, Diogo Onofre; Quincozes-Santos, André

    2015-11-01

    Astrocytes, the most versatile cells of the central nervous system, play an important role in the regulation of neurotransmitter homeostasis, energy metabolism, antioxidant defenses and the anti-inflammatory response. Recently, our group characterized cortical astrocyte cultures from adult Wistar rats. In line with that work, we studied glial function using an experimental in vitro model of aging astrocytes (30 days in vitro after reaching confluence) from newborn (NB), adult (AD) and aged (AG) Wistar rats. We evaluated metabolic parameters, such as the glucose uptake, glutamine synthetase (GS) activity, and glutathione (GSH) content, as well as the GFAP, GLUT-1 and xCT expression. AD and AG astrocytes take up less glucose than NB astrocytes and had decreased GLUT1 expression levels. Furthermore, AD and AG astrocytes exhibited decreased GS activity compared to NB cells. Simultaneously, AD and AG astrocytes showed an increase in GSH levels, along with an increase in xCT expression. NB, AD and AG astrocytes presented similar morphology; however, differences in GFAP levels were observed. Taken together, these results improve the knowledge of cerebral senescence and represent an innovative tool for brain studies of aging. PMID:26210720

  3. The effect of Quinpirol and Sulpiride on the brain activity waves in conscious and aneasthetized rat

    OpenAIRE

    Komaki AR; Alaie H

    1998-01-01

    Brain's waves are produced by spontaneous activity of neurons. These waves are changed by neurotransmitters in the central nervous system (CNS). Concentration of these neurotransmitters can be changed by various drugs and total power of brain waves also increase or decrease by these drugs. In this research effect of Quinpirol and Sulpiride on the brain waves was investigated. Male wistar rats (weight 190-230) were aneasthetized with thiopental and two holes were made into the frontal and...

  4. Potential urinary aging markers of 20-month-old rats.

    Science.gov (United States)

    Li, Xundou; Gao, Youhe

    2016-01-01

    Urine is a very good source for biomarker discovery because it accumulates changes in the body. However, a major challenge in urinary biomarker discovery is the fact that the urinary proteome is influenced by various elements. To circumvent these problems, simpler systems, such as animal models, can be used to establish associations between physiological or pathological conditions and alterations in the urinary proteome. In this study, the urinary proteomes of young (two months old) and old rats (20 months old; nine in each group) were analyzed using LC-MS/MS and quantified using the Progenesis LC-MS software. A total of 371 proteins were identified, 194 of which were shared between the young and old rats. Based on criteria of a fold change ≥2, P humans. However, no shared proteins between our results and the previous aging plasma proteome were identified. Twenty of the 33 (60%) altered proteins have been reported to be disease biomarkers, suggesting that aging may share similar urinary changes with some diseases. The 33 proteins corresponded to 28 human orthologs which, according to the Human Protein Atlas, are strongly expressed in the kidney, intestine, cerebellum and lung. Therefore, the urinary proteome may reflect aging conditions in these organs. PMID:27330854

  5. Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children

    International Nuclear Information System (INIS)

    Altered brain volumes and associations between volumes and developmental outcomes have been reported in prematurely born children. To assess which regional brain volumes are different in very low birth weight (VLBW) children without neurodevelopmental impairments ([NDI] cerebral palsy, hearing loss, blindness and significantly delayed cognitive performance) compared with VLBW children with NDI, and to evaluate the association between regional brain volumes at term-equivalent age and cognitive development and neurological performance at a corrected age of 2 years. The study group consisted of a regional cohort of 164 VLBW children, divided into one group of children without NDI (n = 148) and one group of children with NDI (n = 16). Brain (MRI) was performed at term-equivalent age, from which brain volumes were manually analysed. Cognitive development was assessed with the Bayley Scales of Infant Development II (BSID-II), and neurological performance with the Hammersmith Infant Neurological Examination at the corrected age of 2 years. The volumes of total brain tissue, cerebrum, frontal lobes, basal ganglia and thalami, and cerebellum were significantly smaller, and the volume of the ventricles significantly larger, in the children with NDI than in those without NDI. Even in children without NDI, a smaller cerebellar volume was significantly correlated with poor neurological performance at 2 years of corrected age. Volumetric analysis at brain MRI can provide an additional parameter for early prediction of outcome in VLBW children. (orig.)

  6. Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children

    Energy Technology Data Exchange (ETDEWEB)

    Lind, Annika [Turku University Hospital, Department of Pediatrics, Turku (Finland); Aabo Akademi University, Department of Psychology, Turku (Finland); Parkkola, Riitta [University of Turku and Turku University Hospital, Department of Radiology and Turku PET Center, PO Box 52, Turku (Finland); Lehtonen, Liisa; Maunu, Jonna; Lapinleimu, Helena [University of Turku and Turku University Hospital, Department of Pediatrics, Turku (Finland); Munck, Petriina [Turku University Hospital, Department of Pediatrics, Turku (Finland); University of Turku, Department of Psychology, Turku (Finland); Haataja, Leena [University of Turku and Turku University Hospital, Department of Pediatric Neurology, Turku (Finland)

    2011-08-15

    Altered brain volumes and associations between volumes and developmental outcomes have been reported in prematurely born children. To assess which regional brain volumes are different in very low birth weight (VLBW) children without neurodevelopmental impairments ([NDI] cerebral palsy, hearing loss, blindness and significantly delayed cognitive performance) compared with VLBW children with NDI, and to evaluate the association between regional brain volumes at term-equivalent age and cognitive development and neurological performance at a corrected age of 2 years. The study group consisted of a regional cohort of 164 VLBW children, divided into one group of children without NDI (n = 148) and one group of children with NDI (n = 16). Brain (MRI) was performed at term-equivalent age, from which brain volumes were manually analysed. Cognitive development was assessed with the Bayley Scales of Infant Development II (BSID-II), and neurological performance with the Hammersmith Infant Neurological Examination at the corrected age of 2 years. The volumes of total brain tissue, cerebrum, frontal lobes, basal ganglia and thalami, and cerebellum were significantly smaller, and the volume of the ventricles significantly larger, in the children with NDI than in those without NDI. Even in children without NDI, a smaller cerebellar volume was significantly correlated with poor neurological performance at 2 years of corrected age. Volumetric analysis at brain MRI can provide an additional parameter for early prediction of outcome in VLBW children. (orig.)

  7. In vivo imaging of brain androgen receptors in rats: a [18F]FDHT PET study

    International Nuclear Information System (INIS)

    Introduction: Steroid hormones like androgens play an important role in the development and maintenance of several brain functions. Androgens can act through androgen receptors (AR) in the brain. This study aims to demonstrate the feasibility of positron emission tomography (PET) with 16β-[18F]fluoro-5α-dihydrotestosterone ([18F]FDHT) to image AR expression in the brain. Methods: Male Wistar rats were either orchiectomized to inhibit endogenous androgen production or underwent sham-surgery. Fifteen days after surgery, rats were subjected to a 90-min dynamic [18F]FDHT PET scan with arterial blood sampling. In a subset of orchiectomized rats, 1 mg/kg dihydrotestosterone was co-injected with the tracer in order to saturate the AR. Plasma samples were analyzed for the presence of radioactive metabolites by radio-TLC. Pharmacokinetic modeling was performed to quantify brain kinetics of the tracer. After the PET scan, the animals were terminated for ex-vivo biodistribution. Results: PET imaging and ex vivo biodistribution studies showed low [18F]FDHT uptake in all brain regions, except pituitary. [18F]FDHT uptake in the surrounding cranial bones was high and increased over time. [18F]FDHT was rapidly metabolized in rats. Metabolism was significantly faster in orchiectomized rats than in sham-orchiectomized rats. Quantitative analysis of PET data indicated substantial spill-over of activity from cranial bones into peripheral brain regions, which prevented further analysis of peripheral brain regions. Logan graphical analysis and kinetic modeling using 1- and 2-tissue compartment models showed reversible and homogenously distributed tracer uptake in central brain regions. [18F]FDHT uptake in the brain could not be blocked by endogenous androgens or administration of dihydrotestosterone. Conclusion: The results of this study indicate that imaging of AR availability in rat brain with [18F]FDHT PET is not feasible. The low AR expression in the brain, the rapid metabolism of

  8. [(11)C]-DASB microPET imaging in the aged rat: frontal and meso-thalamic increases in serotonin transporter binding.

    Science.gov (United States)

    Hoekzema, Elseline; Rojas, Santiago; Herance, Raúl; Pareto, Deborah; Abad, Sergio; Jiménez, Xavier; Figueiras, Francisca P; Popota, Foteini; Ruiz, Alba; Flotats, Núria; Fernández, Francisco J; Rocha, Milagros; Rovira, Mariana; Víctor, Víctor M; Gispert, Juan D

    2011-12-01

    Whereas molecular imaging studies in the aging human brain have predominantly demonstrated reductions in serotonin transporter (5-HTT) availability, the majority of the rodent studies, using autoradiographic methods, report increases in neural 5-HTT levels with age. To our knowledge, however, no previous rodent studies have assessed this topic in vivo, and therefore it remains unclear whether this discrepancy arises from methodological or inter-species differences. We performed an [(11)C]-DASB microPET study to evaluate the effects of aging on 5-HTT availability in the rat brain. To generate binding potential estimates, quantitative tracer kinetic modeling was applied using the simplified reference tissue model. A global increase in whole-brain [(11)C]-DASB binding potential was observed in the aged rats in comparison to the control group. More specifically, regional analyses revealed a highly significant increase in 5-HTT binding in the medial frontal cortex, and more modest increments in the midbrain/thalamus. Our results suggest that the frontal cortex represents a site of robust age-related alterations in the rat serotonergic system, and stress the need for further research assessing this topic in the human frontal cortex. Moreover, these findings suggest that the reported discrepancies between rodent and human data may reflect a divergence in the aging processes affecting human and rat serotonergic terminals.

  9. EPA/DHA and vitamin A supplementation improves spatial memory and alleviates the age-related decrease in hippocampal RXRγ and kinase expression in rats

    Directory of Open Access Journals (Sweden)

    Anne eLétondor

    2016-05-01

    Full Text Available Studies suggest that eicosapentaenoic acid (EPA, docosahexaenoic acid (DHA and vitamin A are critical to delay aged-related cognitive decline. These nutrients regulate gene expression in the brain by binding to nuclear receptors such as the retinoid X receptors (RXRs and the retinoic acid receptors (RARs. Moreover, EPA/DHA and retinoids activate notably kinase signaling pathways such as AKT or MAPK, which includes ERK1/2. This suggests that these nutrients may modulate brain function in a similar way. Therefore we investigated in middle-aged rats the behavioral and molecular effects of supplementations with EPA/DHA and vitamin A alone or combined. 18-month-old rats exhibited reference and working memory deficits in the Morris water maze, associated with a decrease in serum vitamin A and hippocampal EPA/DHA contents. RARα, RXRβ and RXRγ mRNA expression and CAMKII, AKT, ERK1/2 expression were decreased in the hippocampus of middle-aged rats. A combined EPA/DHA and vitamin A supplementation had a beneficial additive effect on reference memory but not in working memory in middle-aged rats, associated with an alleviation of the age-related decrease in RXRγ, CAMKII, AKT and ERK1 expression in the hippocampus. This study provides a new combined nutritional strategy to delay brain aging.

  10. EPA/DHA and Vitamin A Supplementation Improves Spatial Memory and Alleviates the Age-related Decrease in Hippocampal RXRγ and Kinase Expression in Rats.

    Science.gov (United States)

    Létondor, Anne; Buaud, Benjamin; Vaysse, Carole; Richard, Emmanuel; Layé, Sophie; Pallet, Véronique; Alfos, Serge

    2016-01-01

    Studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and vitamin A are critical to delay aged-related cognitive decline. These nutrients regulate gene expression in the brain by binding to nuclear receptors such as the retinoid X receptors (RXRs) and the retinoic acid receptors (RARs). Moreover, EPA/DHA and retinoids activate notably kinase signaling pathways such as AKT or MAPK, which includes ERK1/2. This suggests that these nutrients may modulate brain function in a similar way. Therefore, we investigated in middle-aged rats the behavioral and molecular effects of supplementations with EPA/DHA and vitamin A alone or combined. 18-month-old rats exhibited reference and working memory deficits in the Morris water maze, associated with a decrease in serum vitamin A and hippocampal EPA/DHA contents. RARα, RXRβ, and RXRγ mRNA expression and CAMKII, AKT, ERK1/2 expression were decreased in the hippocampus of middle-aged rats. A combined EPA/DHA and vitamin A supplementation had a beneficial additive effect on reference memory but not in working memory in middle-aged rats, associated with an alleviation of the age-related decrease in RXRγ, CAMKII, AKT, and ERK1 expression in the hippocampus. This study provides a new combined nutritional strategy to delay brain aging. PMID:27242514

  11. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    Science.gov (United States)

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

  12. Effects of tetrahydroxystilbene - glucoside on Animal Models of Dementia or Brain Aging

    Institute of Scientific and Technical Information of China (English)

    LinLi; JinChu; LiLiu; LingZhao; LanZhang

    2004-01-01

    Aim: To investigate the effects of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside(TSG) from a Chinese Medicinal Herb polygonum multiflorum on dementia or brain aging. Methods. The brain aging model of mice was developed by s. c. injection of D-galactose (50mg/kg/day) for 60 days. The Alzheimer disease (AD) model of mice

  13. Neuroinflammation not associated with cholinergic degeneration in aged-impaired brain

    OpenAIRE

    McQuail, Joseph A.; Riddle, David R.; Nicolle, Michelle M.

    2010-01-01

    Degeneration of the cholinergic neurons in the basal forebrain and elevation of inflammatory markers are well-established hallmarks of Alzheimer's disease; however, the interplay of these processes in normal aging is not extensively studied. Consequently, we conducted a neuroanatomical investigation to quantify cholinergic neurons and activated microglia in the medial septum/vertical diagonal band (MS/VDB) of young (6 months) and aged (28 months) Fisher 344 × Brown Norway F1 rats. Aged rats i...

  14. Schwann Cells Transplantation Promoted and the Repair of Brain Stem Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    HONG WAN; YI-HUA AN; MEI-ZHEN SUN; YA-ZHUO ZHANG; ZHONG-CHENG WANG

    2003-01-01

    To explore the possibility of Schwann cells transplantation to promote the repair of injured brain stem reticular structure in rats. Methods Schwann cells originated from sciatic nerves of 1 to 2-day-old rats were expanded and labelled by BrdU in vitro, transplanted into rat brain stem reticular structure that was pre-injured by electric needle stimulus. Immunohistochemistry and myelin-staining were used to investigate the expression of BrdU, GAP-43 and new myelination respectively. Results BrdU positive cells could be identified for up to 8 months and their number increased by about 23%, which mainly migrated toward injured ipsilateral cortex. The GAP-43expression reached its peak in 1 month after transplantation and was significantly higher than that in the control group. New myelination could be seen in destructed brain stem areas. Conclusion The transplantation of Schwann cells can promote the restoration of injured brain stem reticular structure.

  15. Glucose metabolism of fetal rat brain in utero, measured with labeled deoxyglucose

    International Nuclear Information System (INIS)

    Mammals have low cerebral metabolic rates immediately after birth and, by inference, also before birth. In this study, we extended the deoxyglucose method to the fetal rat brain in utero. Rate constants for deoxyglucose transfer across the maternal placental and fetal blood-brain barriers, and lumped constant, have not been reported. Therefore, we applied a new method of determining the lumped constant regionally to the fetal rat brain in utero. The lumped constant averaged 0.55 ± 0.15 relative to the maternal circulation. On this basis, we determined the glucose metabolic rate of the fetal rat brain to be one third of the corresponding maternal value, or 19 ± 2 μmol hg-1 min-1. (author)

  16. Upregulated gene expression of local brain-derived neurotrophic factor and nerve growth factor after intracisternal administration of marrow stromal cells in rats with traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    胡德志; 周良辅; 朱剑虹; 毛颖; 吴雪海

    2005-01-01

    Objective: To examine the effects of rat marrow stromal cells (rMSCs) on gene expression of local brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) after injection of rMSCs into Cistern Magnum of adult rats subjected to traumatic brain injury(TBI).Results: Group cell transplantation had higher BDNF and NGF gene expressions than Group saline control during a period of less than 3 weeks (P<0.05).Conclusions: rMSCs transplantation via Cistern Magnum in rats subjected to traumatic brain injury can enhance expressions of local brain NGF and BDNF to a certain extent.

  17. Oxidative state and oxidative metabolism in the brain of rats with adjuvant-induced arthritis.

    Science.gov (United States)

    Wendt, Mariana Marques Nogueira; de Sá-Nakanishi, Anacharis Babeto; de Castro Ghizoni, Cristiane Vizioli; Bersani Amado, Ciomar Aparecida; Peralta, Rosane Marina; Bracht, Adelar; Comar, Jurandir Fernando

    2015-06-01

    The purpose of the present study was to evaluate the oxidative status of the brain of arthritic rats, based mainly on the observation that arthritis induces a pronounced oxidative stress in the liver of arthritis rats and that morphological alterations have been reported to occur in patients with rheumatoid arthritis. Rats with adjuvant-induced arthritis were used. These animals presented higher levels of reactive oxygen species (ROS) in the total brain homogenate (25% higher) and in the mitochondria (+55%) when compared to healthy rats. The nitrite plus nitrate contents, nitric oxide (NO) markers, were also increased in both mitochondria (+27%) and cytosol (+14%). Arthritic rats also presented higher levels of protein carbonyl groups in the total homogenate (+43%), mitochondria (+69%) and cytosol (+145%). Arthritis caused a diminution of oxygen consumption in isolated brain mitochondria only when ascorbate was the electron donor. The disease diminished the mitochondrial cytochrome c oxidase activity by 55%, but increased the transmembrane potential by 16%. The pro-oxidant enzyme xanthine oxidase was 150%, 110% and 283% higher, respectively, in the brain homogenate, mitochondria and cytosol of arthritic animals. The same occurred with the calcium-independent NO-synthase activity that was higher in the brain homogenate (90%) and cytosol (122%) of arthritic rats. The catalase activity, on the other hand, was diminished by arthritis in all cellular fractions (between 30 and 40%). It is apparent that the brain of rats with adjuvant-induced arthritis presents a pronounced oxidative stress and a significant injury to lipids and proteins, a situation that possibly contributes to the brain symptoms of the arthritis disease.

  18. Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction.

    Science.gov (United States)

    Liu, J; Liu, L; Chen, H

    2011-05-01

    Changes in brain ultrastructure of fetal rats with intrauterine growth restriction (IUGR) were explored and the effects of antenatal taurine supplementation on their brain ultrastructure were determined. Fifteen pregnant rats were randomly divided into three groups: control group, IUGR model group and IUGR group given antenatal taurine supplements. Taurine was added to the diet of the taurine group at a dose of 300 mg/kg/d from 12 days after conception until natural delivery. Transmission electron microscopy was used to observe ultrastructural changes in the brains of the newborn rats. At the same time, brain cellular apoptosis was detected using TUNEL, and the changes in protein expression of neuron specific enolase and glial fibrillary acidic protein were analyzed using immunohistochemistry. The results showed that: 1) The average body weight and cerebral weight were significantly lower in the IUGR group than in the control group (ptaurine was supplemented (ptaurine supplementation. 3) The results of TUNEL showed that the counts of apoptotic brain cells in IUGR groups were significantly increased from those in control groups and that taurine could significantly decrease brain cell apoptosis (ptaurine-supplementation could significantly increase the counts of neuron specific enolase and glial fibrillary acidic protein immunoreactive cells in fetal rats with IUGR (ptaurine can significantly improve the IUGR fetal brain development.

  19. Action of the pyrethroid insecticide cypermethrin on rat brain IIa sodium channels expressed in xenopus oocytes.

    Science.gov (United States)

    Smith, T J; Soderlund, D M

    1998-12-01

    Pyrethroid insecticides bind to a unique site on voltage-dependent sodium channels and prolong sodium currents, leading to repetitive bursts of action potentials or use-dependent nerve block. To further characterize the site and mode of action of pyrethroids on sodium channels, we injected synthetic mRNA encoding the rat brain IIa sodium channel alpha subunit, either alone or in combination with synthetic mRNA encoding the rat sodium channel beta1 subunit, into oocytes of the frog Xenopus laevis and assessed the actions of the pyrethroid insecticide [1R,cis,alphaS]-cypermethrin on expressed sodium currents by two-electrode voltage clamp. In oocytes expressing only the rat brain IIa alpha subunit, cypermethrin produced a slowly-decaying sodium tail current following a depolarizing pulse. In parallel experiments using oocytes expressing the rat brain IIa alpha subunit in combination with the rat beta1 subunit, cypermethrin produced qualitatively similar tail currents following a depolarizing pulse and also induced a sustained component of the sodium current measured during a step depolarization of the oocyte membrane. The voltage dependence of activation and steady-state inactivation of the cypermethrin-dependent sustained current were identical to those of the peak transient sodium current measured in the absence of cypermethrin. Concentration-response curves obtained using normalized tail current amplitude as an index of the extent of sodium channel modification by cypermethrin revealed that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit increased the apparent affinity of the sodium channel binding site for cypermethrin by more than 20-fold. These results confirm that the pyrethroid binding site is intrinsic to the sodium channel alpha subunit and demonstrate that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit alters the apparent affinity of this site for pyrethroids.

  20. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    Science.gov (United States)

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR. PMID:24676564

  1. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    Science.gov (United States)

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR.

  2. Glucocorticoids modulate the NGF mRNA response in the rat hippocampus after traumatic brain injury.

    Science.gov (United States)

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2001-02-23

    Nerve growth factor (NGF) expression in the rat hippocampus is increased after experimental traumatic brain injury (TBI) and is neuroprotective. Glucocorticoids are regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on the expression of NGF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury and in situ hybridisation to evaluate the expression of NGF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomised rats (with or without CORT replacement). TBI increased expression of NGF mRNA in sham-ADX rats, but not in ADX rats. Furthermore, CORT replacement in ADX rats restored the increase in NGF mRNA induced by TBI. These findings suggest that glucocorticoids have an important role in the induction of hippocampal NGF mRNA after TBI.

  3. Protection of GBE50 on brain mitochondria in rats with hyperlipidemia

    Institute of Scientific and Technical Information of China (English)

    KaiSUN; GangLIU; Yun-xuanZHANG; Ghen-liangYIN; Gaj-junTIAN; Jia-huPAN

    2005-01-01

    AIM To study the protective effects of the new standardized preparation of Ginkgo biloba extracts(GBE50) anainst brain mitochondrial damages induced by hyperlipemia in rats. METHODS Rat model with hyperlipemia was established by feeding the young male SD rats (3 weeks after born) with high lipid food for 3 months. Then the rats were treated with different dosage of GBE50(ig) for 4 weeks. The prophylaxis rat group were fed with the mixture of high lipid food and GBE50 (50mg/kg/d). The brain mitochondria was separated for determination of the R3, R4 and RCR of the respiration function with the method of Clark's electrode. The mitochondrial transmembrane potential(Δψm) was derected by the Rho123 assay and the cytochrome c release was checked by spectrography. In addition, the parameters of oxidative stress (the activities of SOD, GSH-Px, and the MDA leve) and the activities of ATPase were assayed.

  4. Cerebrovascular and blood-brain barrier morphology in spontaneously hypertensive rats: effect of treatment with choline alphoscerate.

    Science.gov (United States)

    Tayebati, Seyed Khosrow; Amenta, Francesco; Tomassoni, Daniele

    2015-01-01

    Cholinergic precursors increasing choline availability and acetylcholine synthesis/release may represent a therapeutic approach for countering cognitive impairment occurring in adult-onset dementia disorders. Choline alphoscerate (alpha-gliceryl-phosphoryl-choline, GPC) is among cholinergic precursors the most effective in enhancing acetylcholine biosynthesis and release in animal models. This study was designed to assess if a long-term treatment with GPC modify cerebrovascular components [perivascular astrocytes, blood-brain barrier (BBB) and microvessels] and endothelial inflammatory markers expression in spontaneously hypertensive rats (SHR) used as a model of brain vascular injury. Male SHR aged 32 weeks and age-matched normotensive Wistar-Kyoto rats were treated for 4 weeks with GPC (150 mg/kg/day) or a vehicle. Intracerebral arteries of different brain areas, perivascular astrocytes, BBB and endothelial inflammatory markers were assessed by quantitative morphological and immunohistochemical techniques. No significant changes in the size of perivascular astrocytes were observed in SHR versus normotensive Wistar-Kyoto rats, whereas the expression of the BBB marker aquaporin-4 increased in SHR. This phenomenon was countered by GPC treatment. On the contrary, GPC has no vasodilator effect on brain micro-vessels. Endothelial markers and vascular adhesion molecules expression were not homogeneously affected by hypertension and GPC treatment in intracerebral vessels. The observation that treatment with GPC reversed BBB changes and countered to some extent micro-vessels changes occurring in SHR could explain data of clinical trials reporting an improvement of cognitive function in subjects suffering from cerebrovascular disorders and treated with GPC. These preclinical data suggest that the compound could have a cerebrovascular protective effect deserving a further characterization. PMID:25714975

  5. The brain response to peripheral insulin declines with age: a contribution of the blood-brain barrier?

    Directory of Open Access Journals (Sweden)

    Tina Sartorius

    Full Text Available It is a matter of debate whether impaired insulin action originates from a defect at the neural level or impaired transport of the hormone into the brain. In this study, we aimed to investigate the effect of aging on insulin concentrations in the periphery and the central nervous system as well as its impact on insulin-dependent brain activity.Insulin, glucose and albumin concentrations were determined in 160 paired human serum and cerebrospinal fluid (CSF samples. Additionally, insulin was applied in young and aged mice by subcutaneous injection or intracerebroventricularly to circumvent the blood-brain barrier. Insulin action and cortical activity were assessed by Western blotting and electrocorticography radiotelemetric measurements.In humans, CSF glucose and insulin concentrations were tightly correlated with the respective serum/plasma concentrations. The CSF/serum ratio for insulin was reduced in older subjects while the CSF/serum ratio for albumin increased with age like for most other proteins. Western blot analysis in murine whole brain lysates revealed impaired phosphorylation of AKT (P-AKT in aged mice following peripheral insulin stimulation whereas P-AKT was comparable to levels in young mice after intracerebroventricular insulin application. As readout for insulin action in the brain, insulin-mediated cortical brain activity instantly increased in young mice subcutaneously injected with insulin but was significantly reduced and delayed in aged mice during the treatment period. When insulin was applied intracerebroventricularly into aged animals, brain activity was readily improved.This study discloses age-dependent changes in insulin CSF/serum ratios in humans. In the elderly, cerebral insulin resistance might be partially attributed to an impaired transport of insulin into the central nervous system.

  6. BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE

    OpenAIRE

    Cunnane, SC; NUGENT, S; Roy, M.; Courchesne-Loyer, A; Croteau, E; Tremblay, S.; Castellano, A.; Pifferi, F.; Bocti, C; Paquet, N; Begdouri, H; Bentourkia, M; Turcotte, E; M. Allard; Barberger-Gateau, P

    2010-01-01

    Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may in...

  7. In vivo study about specific captation of 125 I-insulin by rat brain structures

    International Nuclear Information System (INIS)

    The specific captation of 125 I-insulin was evaluated by brain structures, as olfactory bulbous, hypothalamus and cerebellum in rats, from in vivo experiences that including two different aspects: captation measure of 125 I-insulin after the intravenous injection of the labelled hormone, in fed rats and in rats with 48 h of fast or convulsion, procedure by the pentylene tetrazole; captation measure of 125 I-insulin after intra-cerebral-ventricular injection of the labelled hormone in fed rats. (C.G.C.)

  8. METABOLIC RATE AS A FUNCTION OF AGE IN BROWN NORWAY AND LONG-EVANS RATS.

    Science.gov (United States)

    Brown Norway (BN) rats are commonly used in aging studies but relatively little is known on their metabolism as it varies with age. In fact, there is considerable disagreement on the wholebody metabolism of aging rats with some studies indicating a decrease and others showing an...

  9. Chronic vitamin C deficiency does not accelerate oxidative stress in ageing brains of guinea pigs

    DEFF Research Database (Denmark)

    Tveden-Nyborg, Pernille; Andersen, Stine Hasselholt; Miyashita, Namiyo;

    2012-01-01

    , a lack of vitamin C could be associated with an increase in redox imbalance in the ageing brain. The present study compared oxidative stress of ageing to that of a long-term non-scorbutic vitamin C deficiency in guinea pigs. Adults (3-9 months old) were compared to old (36-42 months old) animals during...... a six-month dietary intervention by assessing vitamin C transport and redox homeostasis in the brain. In contrast to our hypothesis, chronic vitamin C deficiency did not affect the measured markers of oxidative stress in the brains of adult and aged animals. However, aged animals generally showed...

  10. Atorvastatin prevents age-related and amyloid-β-induced microglial activation by blocking interferon-γ release from natural killer cells in the brain

    Directory of Open Access Journals (Sweden)

    Clarke Rachael

    2011-03-01

    Full Text Available Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-γ (IFNγ. IFNγ has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-β (Aβ on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFNγ, IL-2, monocyte chemoattractant protein-1 (MCP-1 and IFNγ-induced protein 10 kDa (IP-10, expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK cells are a major source of IFNγ in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and Aβ-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2 by releasing IFNγ. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and Aβ-treated rats. This was paralleled by a decrease in IFNγ, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and Aβ-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.

  11. Atorvastatin prevents age-related and amyloid-beta-induced microglial activation by blocking interferon-gamma release from natural killer cells in the brain

    LENUS (Irish Health Repository)

    Lyons, Anthony

    2011-03-31

    Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-γ (IFNγ). IFNγ has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-β (Aβ) on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFNγ, IL-2, monocyte chemoattractant protein-1 (MCP-1) and IFNγ-induced protein 10 kDa (IP-10)), expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK) cells are a major source of IFNγ in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and Aβ-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2) by releasing IFNγ. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and Aβ-treated rats. This was paralleled by a decrease in IFNγ, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and Aβ-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  13. Quantitative autoradiography of (/sup 3/H)corticosterone receptors in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Sapolsky, R.M.; McEwen, B.S. (Rockefeller Univ., New York (USA)); Rainbow, T.C. (Pennsylvania Univ., Philadelphia (USA). School of Medicine)

    1983-07-25

    The authors have quantified corticosterone receptors in rat brain by optical density measurements of tritium-film autoradiograms. Rats were injected i.v. with 500 ..mu..Ci (/sup 3/H)corticosterone to label brain receptors. Frozen sections of brain were cut with a cryostat and exposed for 2 months against tritium-sensitive sheet film (LKB Ultrofilm). Tritium standards were used to convert optical density readings into molar concentrations of receptor. High levels of corticosterone receptors were present throughout the pyramidal and granule cell layers of the hippocampus. Moderate levels of receptors were found in the neuropil of the hippocampus, the lateral septum, the cortical nucleus of the amygdala and the entorhinal cortex. All other brain regions had low levels of receptors. These results extend previous non-quantitative autoradiographic studies of corticosterone receptors and provide a general procedure for the quantitative autoradiography of steroid hormone receptors in brain tissue.

  14. Photoacoustic imaging to detect rat brain activation after cocaine hydrochloride injection

    Science.gov (United States)

    Jo, Janggun; Yang, Xinmai

    2011-03-01

    Photoacoustic imaging (PAI) was employed to detect small animal brain activation after the administration of cocaine hydrochloride. Sprague Dawley rats were injected with different concentrations (2.5, 3.0, and 5.0 mg per kg body) of cocaine hydrochloride in saline solution through tail veins. The brain functional response to the injection was monitored by photoacoustic tomography (PAT) system with horizontal scanning of cerebral cortex of rat brain. Photoacoustic microscopy (PAM) was also used for coronal view images. The modified PAT system used multiple ultrasonic detectors to reduce the scanning time and maintain a good signal-to-noise ratio (SNR). The measured photoacoustic signal changes confirmed that cocaine hydrochloride injection excited high blood volume in brain. This result shows PAI can be used to monitor drug abuse-induced brain activation.

  15. The food-conditioned place preference task in adolescent, adult and aged rats of both sexes

    OpenAIRE

    Rubinow, Marisa J.; Hagerbaumer, Diana A.; Juraska, Janice M.

    2008-01-01

    The rat basolateral amygdala shows neuroanatomical sex differences, continuing development after puberty and aging-related alterations. Implications for amygdala-dependent memory processes were explored here by testing male and female hooded rats in adolescence, adulthood and old age on the food-conditioned place preference task. While aged rats were unimpaired, adolescents failed to learn the task. This finding may be related to ongoing development of the basolateral amygdala and related mem...

  16. Age-dependent pharmacokinetic and pharmacodynamic response in preweanling rats following oral exposure to the organophosphorus insecticide chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.

    2006-03-01

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to CPF-oxon and 3,5,6-trichloro-2-pyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. The pharmacokinetics of CPF, TCP, and the extent of blood (plasma/RBC), and brain ChE inhibition in rats were determined on postnatal days (PND) -5, -12, and -17 following oral gavage administration of 1 and 10 mg CPF/kg of body weight. For all neonatal ages the blood TCP exceeded the CPF concentration, and within each age group there was no evidence of non-linear kinetics over the dose range evaluated. Younger animals demonstrated a greater sensitivity to ChE inhibition as evident by the dose- and age-dependent inhibition of plasma, RBC, and brain ChE. Of particular importance was the observation that even in rats as young as PND-5, the CYP450 metabolic capacity was adequate to metabolize CPF to both TCP and CPF-oxon based on the detection of TCP in blood and extensive ChE inhibition (biomarker of CPF-oxon) at all ages. In addition, the increase in the blood TCP concentration ({approx}3-fold) in PND-17 rats relative to the response in the younger animals, and the higher blood concentrations of CPF in neonatal rats (1.7 to 7.5-fold) relative to adults was consistent with an increase in CYP450 metabolic capacity with age. This is the first reported study that evaluated both the pharmacokinetics of the parent pesticide, the major metabolite and the extent of ChE inhibition dynamics in the same animals as a function of neonatal age. The results suggest that in the neonatal rat, CPF was rapidly absorbed and metabolized, and the extent of metabolism was age-dependent.

  17. CT ASSESSMENT OF BRAIN VENTRICULAR SIZE BASED ON AGE AND SEX: A STUDY OF 112 CASES

    Directory of Open Access Journals (Sweden)

    Vinoo

    2013-12-01

    Full Text Available CT being the primary modality of choice in many centers for the diagnosis of brain pathology, normal brain ventricular size measurem ents is an important parameter for the diagnosis of conditions like hydrocephalus, age related atrophic changes and also other brain pathologies producing ventriculomegaly. It is also important for knowing the normal upper and lower limits of the brain ven tricular system in the different age groups, and in both sexes so as to diagnose brain pathology.The ventricular system of the brain undergoes changes with aging and varies with gender.Our study consists of 48 female, and 64 male patients. Apart from the v entricular measurements, two ratios and two indices were also calculated – which included the right and left Evan’s ratio, CM index, and ventricular size inde

  18. HRT and its effect on normal ageing of the brain and dementia

    Science.gov (United States)

    Compton, Jacqueline; van Amelsvoort, Therese; Murphy, Declan

    2001-01-01

    There are significant gender differences in human brain disease. For example, females are significantly more likely to suffer from Alzheimer's disease (AD) than men (even after correcting for differences in life expectancy), and females on hormone replacement therapy (HRT) are significantly less likely to suffer from Alzheimer's disease than women who do not take HRT. However the neurobiological basis to these differences in clinical brain disease were unknown until relatively recently. In this review we will discuss results of studies that show; (i) gender differences in human brain disease are most likely to be explained by gender differences in brain development and ageing; (ii) sex steroids have a significant effect on the brain; (iii) sex steroids are crucial to the development and ageing of brain regions affected in age-related brain diseases (for example AD); (iv) sex steroids interact with neuronal networks and chemical systems at many different levels; (v) sex steroids affect cognitive function in elderly women. Thus, the current literature supports the hypothesis that sex steroids can modulate brain ageing, and this provides a neurobiological explanation for the significantly higher prevalence of AD in females who do not take HRT, and may lead to new treatment approaches for age-related brain disease including AD. PMID:11736875

  19. Transcriptome analysis of amoeboid and ramified microglia isolated from the corpus callosum of rat brain

    Directory of Open Access Journals (Sweden)

    Parakalan Rangarajan

    2012-06-01

    Full Text Available Abstract Background Microglia, the resident immune cells of the central nervous system (CNS, have two distinct phenotypes in the developing brain: amoeboid form, known to be amoeboid microglial cells (AMC and ramified form, known to be ramified microglial cells (RMC. The AMC are characterized by being proliferative, phagocytic and migratory whereas the RMC are quiescent and exhibit a slow turnover rate. The AMC transform into RMC with advancing age, and this transformation is indicative of the gradual shift in the microglial functions. Both AMC and RMC respond to CNS inflammation, and they become hypertrophic when activated by trauma, infection or neurodegenerative stimuli. The molecular mechanisms and functional significance of morphological transformation of microglia during normal development and in disease conditions is not clear. It is hypothesized that AMC and RMC are functionally regulated by a specific set of genes encoding various signaling molecules and transcription factors. Results To address this, we carried out cDNA microarray analysis using lectin-labeled AMC and RMC isolated from frozen tissue sections of the corpus callosum of 5-day and 4-week old rat brain respectively, by laser capture microdissection. The global gene expression profiles of both microglial phenotypes were compared and the differentially expressed genes in AMC and RMC were clustered based on their functional annotations. This genome wide comparative analysis identified genes that are specific to AMC and RMC. Conclusions The novel and specific molecules identified from the trancriptome explains the quiescent state functioning of microglia in its two distinct morphological states.

  20. Standardized environmental enrichment supports enhanced brain plasticity in healthy rats and prevents cognitive impairment in epileptic rats.

    Directory of Open Access Journals (Sweden)

    Raafat P Fares

    Full Text Available Environmental enrichment of laboratory animals influences brain plasticity, stimulates neurogenesis, increases neurotrophic factor expression, and protects against the effects of brain insult. However, these positive effects are not constantly observed, probably because standardized procedures of environmental enrichment are lacking. Therefore, we engineered an enriched cage (the Marlau™ cage, which offers: (1 minimally stressful social interactions; (2 increased voluntary exercise; (3 multiple entertaining activities; (4 cognitive stimulation (maze exploration, and (5 novelty (maze configuration changed three times a week. The maze, which separates food pellet and water bottle compartments, guarantees cognitive stimulation for all animals. Compared to rats raised in groups in conventional cages, rats housed in Marlau™ cages exhibited increased cortical thickness, hippocampal neurogenesis and hippocampal levels of transcripts encoding various genes involved in tissue plasticity and remodeling. In addition, rats housed in Marlau™ cages exhibited better performances in learning and memory, decreased anxiety-associated behaviors, and better recovery of basal plasma corticosterone level after acute restraint stress. Marlau™ cages also insure inter-experiment reproducibility in spatial learning and brain gene expression assays. Finally, housing rats in Marlau™ cages after severe status epilepticus at weaning prevents the cognitive impairment observed in rats subjected to the same insult and then housed in conventional cages. By providing a standardized enriched environment for rodents during housing, the Marlau™ cage should facilitate the uniformity of environmental enrichment across laboratories.

  1. Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury.

    Science.gov (United States)

    Robinson, Shenandoah; Winer, Jesse L; Berkner, Justin; Chan, Lindsay A S; Denson, Jesse L; Maxwell, Jessie R; Yang, Yirong; Sillerud, Laurel O; Tasker, Robert C; Meehan, William P; Mannix, Rebekah; Jantzie, Lauren L

    2016-06-01

    OBJECTIVE Traumatic brain injury (TBI) is a leading cause of death and severe morbidity for otherwise healthy full-term infants around the world. Currently, the primary treatment for infant TBI is supportive, as no targeted therapies exist to actively promote recovery. The developing infant brain, in particular, has a unique response to injury and the potential for repair, both of which vary with maturation. Targeted interventions and objective measures of therapeutic efficacy are needed in this special population. The authors hypothesized that MRI and serum biomarkers can be used to quantify outcomes following infantile TBI in a preclinical rat model and that the potential efficacy of the neuro-reparative agent erythropoietin (EPO) in promoting recovery can be tested using these biomarkers as surrogates for functional outcomes. METHODS With institutional approval, a controlled cortical impact (CCI) was delivered to postnatal Day (P)12 rats of both sexes (76 rats). On postinjury Day (PID)1, the 49 CCI rats designated for chronic studies were randomized to EPO (3000 U/kg/dose, CCI-EPO, 24 rats) or vehicle (CCI-veh, 25 rats) administered intraperitoneally on PID1-4, 6, and 8. Acute injury (PID3) was evaluated with an immunoassay of injured cortex and serum, and chronic injury (PID13-28) was evaluated with digitized gait analyses, MRI, and serum immunoassay. The CCI-veh and CCI-EPO rats were compared with shams (49 rats) primarily using 2-way ANOVA with Bonferroni post hoc correction. RESULTS Following CCI, there was 4.8% mortality and 55% of injured rats exhibited convulsions. Of the injured rats designated for chronic analyses, 8.1% developed leptomeningeal cyst-like lesions verified with MRI and were excluded from further study. On PID3, Western blot showed that EPO receptor expression was increased in the injured cortex (p = 0.008). These Western blots also showed elevated ipsilateral cortex calpain degradation products for αII-spectrin (αII-SDPs; p < 0

  2. Magnetic resonance imaging indicators of blood-brain barrier and brain water changes in young rats with kaolin-induced hydrocephalus

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    Del Bigio Marc R

    2011-08-01

    Full Text Available Abstract Background Hydrocephalus is associated with enlargement of cerebral ventricles. We hypothesized that magnetic resonance (MR imaging parameters known to be influenced by tissue water content would change in parallel with ventricle size in young rats and that changes in blood-brain barrier (BBB permeability would be detected. Methods Hydrocephalus was induced by injection of kaolin into the cisterna magna of 4-week-old rats, which were studied 1 or 3 weeks later. MR was used to measure longitudinal and transverse relaxation times (T1 and T2 and apparent diffusion coefficients in several regions. Brain tissue water content was measured by the wet-dry weight method, and tissue density was measured in Percoll gradient columns. BBB permeability was measured by quantitative imaging of changes on T1-weighted images following injection of gadolinium diethylenetriamine penta-acetate (Gd-DTPA tracer and microscopically by detection of fluorescent dextran conjugates. Results In nonhydrocephalic rats, water content decreased progressively from age 3 to 7 weeks. T1 and T2 and apparent diffusion coefficients did not exhibit parallel changes and there was no evidence of BBB permeability to tracers. The cerebral ventricles enlarged progressively in the weeks following kaolin injection. In hydrocephalic rats, the dorsal cortex was more dense and the white matter less so, indicating that the increased water content was largely confined to white matter. Hydrocephalus was associated with transient elevation of T1 in gray and white matter and persistent elevation of T2 in white matter. Changes in the apparent diffusion coefficients were significant only in white matter. Ventricle size correlated significantly with dorsal water content, T1, T2, and apparent diffusion coefficients. MR imaging showed evidence of Gd-DTPA leakage in periventricular tissue foci but not diffusely. These correlated with microscopic leak of larger dextran tracers. Conclusions MR

  3. Brain activation patterns at exhaustion in rats that differ in inherent exercise capacity.

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    Teresa E Foley

    Full Text Available In order to further understand the genetic basis for variation in inherent (untrained exercise capacity, we examined the brains of 32 male rats selectively bred for high or low running capacity (HCR and LCR, respectively. The aim was to characterize the activation patterns of brain regions potentially involved in differences in inherent running capacity between HCR and LCR. Using quantitative in situ hybridization techniques, we measured messenger ribonuclease (mRNA levels of c-Fos, a marker of neuronal activation, in the brains of HCR and LCR rats after a single bout of acute treadmill running (7.5-15 minutes, 15° slope, 10 m/min or after treadmill running to exhaustion (15-51 minutes, 15° slope, initial velocity 10 m/min. During verification of trait differences, HCR rats ran six times farther and three times longer prior to exhaustion than LCR rats. Running to exhaustion significantly increased c-Fos mRNA activation of several brain areas in HCR, but LCR failed to show significant elevations of c-Fos mRNA at exhaustion in the majority of areas examined compared to acutely run controls. Results from these studies suggest that there are differences in central c-Fos mRNA expression, and potential brain activation patterns, between HCR and LCR rats during treadmill running to exhaustion and these differences could be involved in the variation in inherent running capacity between lines.

  4. Brain activation patterns at exhaustion in rats that differ in inherent exercise capacity.

    Science.gov (United States)

    Foley, Teresa E; Brooks, Leah R; Gilligan, Lori J; Burghardt, Paul R; Koch, Lauren G; Britton, Steven L; Fleshner, Monika

    2012-01-01

    In order to further understand the genetic basis for variation in inherent (untrained) exercise capacity, we examined the brains of 32 male rats selectively bred for high or low running capacity (HCR and LCR, respectively). The aim was to characterize the activation patterns of brain regions potentially involved in differences in inherent running capacity between HCR and LCR. Using quantitative in situ hybridization techniques, we measured messenger ribonuclease (mRNA) levels of c-Fos, a marker of neuronal activation, in the brains of HCR and LCR rats after a single bout of acute treadmill running (7.5-15 minutes, 15° slope, 10 m/min) or after treadmill running to exhaustion (15-51 minutes, 15° slope, initial velocity 10 m/min). During verification of trait differences, HCR rats ran six times farther and three times longer prior to exhaustion than LCR rats. Running to exhaustion significantly increased c-Fos mRNA activation of several brain areas in HCR, but LCR failed to show significant elevations of c-Fos mRNA at exhaustion in the majority of areas examined compared to acutely run controls. Results from these studies suggest that there are differences in central c-Fos mRNA expression, and potential brain activation patterns, between HCR and LCR rats during treadmill running to exhaustion and these differences could be involved in the variation in inherent running capacity between lines. PMID:23028992

  5. INFLUENCE OF ACUPUNCTURE ON BRAIN-TAXIS OF TETRAMETHYLPYRAZINE IN ACUTE CEREBRAL INFARCTION RATS

    Institute of Scientific and Technical Information of China (English)

    崔荣秀; 陈以国; 谷雨

    2003-01-01

    Purpose: To observe the effect of acupuncture on the brain-taxis of tetrarmethylpyrazine (TMP) and toexplore into the underlying mechanisms of combined action of acupuncture and medicine in the treatment of acute cere-bral ischemia. Methods: 37 male Wistar rats were randomly divided into normal control group (n= 10), sham-operationgroup (n= 10), acute cerebral ischemia (ACI) + drug group (model group, n=8)and ACl+drug+acupuncture group(acupuncture group, n=9). Rat ACl model was established by using photochemical method. "Neiguan"(PC 6) and"Shuigou"(GV 26) were punctured and stimulated with both hand manipulation and electroacupuncture, 30 min and16hrs after ACI. TMP was given to the rats of the later 2 groups using gastric perfusion method. High pressure chro-matography (HPLC) was used to detect the target absorption level of TMP in the brain. Results: The content of TMP inthe brain in acupuncture group was significantly higher than that in model group (P<0.01), suggesting that acupunc-ture can strengthen the brain-taxis of TMP in ACl rats, and combined administration of acupuncture and Chinese drugmaybe work better for treatment of acute cerebral infarction. Conclusion: Acupuncture can strengthen the chano-taxisof TMP to the brain in ACl rats.

  6. Neuroanatomy-based matrix-guided trimming protocol for the rat brain.

    Science.gov (United States)

    Defazio, Rossella; Criado, Ana; Zantedeschi, Valentina; Scanziani, Eugenio

    2015-02-01

    Brain trimming through defined neuroanatomical landmarks is recommended to obtain consistent sections in rat toxicity studies. In this article, we describe a matrix-guided trimming protocol that uses channels to reproduce coronal levels of anatomical landmarks. Both setup phase and validation study were performed on Han Wistar male rats (Crl:WI(Han)), 10-week-old, with bodyweight of 298 ± 29 (SD) g, using a matrix (ASI-Instruments(®), Houston, TX) fitted for brains of rats with 200 to 400 g bodyweight. In the setup phase, we identified eight channels, that is, 6, 8, 10, 12, 14, 16, 19, and 21, matching the recommended landmarks midway to the optic chiasm, frontal pole, optic chiasm, infundibulum, mamillary bodies, midbrain, middle cerebellum, and posterior cerebellum, respectively. In the validation study, we trimmed the immersion-fixed brains of 60 rats using the selected channels to determine how consistently the channels reproduced anatomical landmarks. Percentage of success (i.e., presence of expected targets for each level) ranged from 89 to 100%. Where 100% success was not achieved, it was noted that the shift in brain trimming was toward the caudal pole. In conclusion, we developed and validated a trimming protocol for the rat brain that allow comparable extensiveness, homology, and relevance of coronal sections as the landmark-guided trimming with the advantage of being quickly learned by technicians. PMID:24947989

  7. Probing Intrinsic Resting-State Networks in the Infant Rat Brain

    Science.gov (United States)

    Bajic, Dusica; Craig, Michael M.; Borsook, David; Becerra, Lino

    2016-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) measures spontaneous fluctuations in blood oxygenation level-dependent (BOLD) signal in the absence of external stimuli. It has become a powerful tool for mapping large-scale brain networks in humans and animal models. Several rs-fMRI studies have been conducted in anesthetized and awake adult rats, reporting consistent patterns of brain activity at the systems level. However, the evolution to adult patterns of resting-state activity has not yet been evaluated and quantified in the developing rat brain. In this study, we hypothesized that large-scale intrinsic networks would be easily detectable but not fully established as specific patterns of activity in lightly anesthetized 2-week-old rats (N = 11). Independent component analysis (ICA) identified 8 networks in 2-week-old-rats. These included Default mode, Sensory (Exteroceptive), Salience (Interoceptive), Basal Ganglia-Thalamic-Hippocampal, Basal Ganglia, Autonomic, Cerebellar, as well as Thalamic-Brainstem networks. Many of these networks consisted of more than one component, possibly indicative of immature, underdeveloped networks at this early time point. Except for the Autonomic network, infant rat networks showed reduced connectivity with subcortical structures in comparison to previously published adult networks. Reported slow fluctuations in the BOLD signal that correspond to functionally relevant resting-state networks in 2-week-old rats can serve as an important tool for future studies of brain development in the settings of different pharmacological applications or disease. PMID:27803653

  8. Acetaldehyde metabolism by brain mitochondria from UChA and UChB rats.

    Science.gov (United States)

    Quintanilla, M E; Tampier, L

    1995-01-01

    The acetaldehyde (AcH) oxidizing capacity of total brain homogenates from the genetically high-ethanol consumer (UChB) appeared to be greater than that of the low-ethanol consumer (UChA) rats. To gain further information about this strain difference, the activity of aldehyde dehydrogenase (AIDH) in different subcellular fractions of whole brain homogenates from naive UChA and UChB rat strains of both sexes has been studied by measuring the rate of AcH disappearance and by following the reduction of NAD to NADH. The results demonstrated that the higher capacity of brain homogenates from UChB rats to oxidize AcH when compared to UChA ones was because the UChB mitochondrial low Km AIDH exhibits a much greater affinity for NAD than that of the UChA rats, as evidenced by four-to fivefold differences in the Km values for NAD. But the dehydrogenases from both strains exhibited a similar maximum rate at saturating NAD concentrations. Because intact brain mitochondria isolated from UChB rats oxidized AcH at a higher rate than did mitochondria from UChA rats only in state 4, but not in state 3, this strain difference in AIDH activity might be restricted in vivo to NAD disposition.

  9. Nutraceutical intervention reverses the negative effects of blood from aged rats on stem cells.

    Science.gov (United States)

    Bickford, Paula C; Kaneko, Yuji; Grimmig, Bethany; Pappas, Colleen; Small, Brent; Sanberg, Cyndy D; Sanberg, Paul R; Tan, Jun; Douglas Shytle, R

    2015-10-01

    Aging is associated with a decline in function in many of the stem cell niches of the body. An emerging body of literature suggests that one of the reasons for this decline in function is due to cell non-autonomous influences on the niche from the body. For example, studies using the technique of parabiosis have demonstrated a negative influence of blood from aged mice on muscle satellite cells and neurogenesis in young mice. We examined if we could reverse this effect of aged serum on stem cell proliferation by treating aged rats with NT-020, a dietary supplement containing blueberry, green tea, vitamin D3, and carnosine that has been shown to increase neurogenesis in aged rats. Young and aged rats were administered either control NIH-31 diet or one supplemented with NT-020 for 28 days, and serum was collected upon euthanasia. The serum was used in cultures of both rat hippocampal neural progenitor cells (NPCs) and rat bone marrow-derived mesenchymal stem cells (MSCs). Serum from aged rats significantly reduced cell proliferation as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-bromo-2'-deoxyuridine (BrdU) assays in both NPCs and MSCs. Serum from aged rats treated with NT-020 was not different from serum from young rats. Therefore, NT-020 rescued the effect of serum from aged rats to reduce stem cell proliferation. PMID:26410618

  10. Enriched environment induces higher CNPase positive cells in aged rat hippocampus.

    Science.gov (United States)

    Zhao, Yuan-Yu; Shi, Xiao-Yan; Zhang, Lei; Wu, Hong; Chao, Feng-Lei; Huang, Chun-Xia; Gao, Yuan; Qiu, Xuan; Chen, Lin; Lu, Wei; Tang, Yong

    2013-10-25

    It had been reported that enriched environment was beneficial for the brain cognition and for the neurons and synapses in hippocampus. Previous study reported that the oligodendrocyte density in hippocampus was increased when the rats were reared in the enriched environment from weaning to adulthood. However, biological conclusions based on density were difficult to interpret because the changes in density could be due to an alteration of total quantity and/or an alteration in the reference volume. In the present study, we used unbiased stereological methods to investigate the effect of enriched environment on the total number of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) positive cells in CA1 and dentate gyrus (DG) of the hippocampus in aged rats. Our results indicated that there was significant difference in the total numbers of CNPase positive cells in both CA1 and DG between enriched environment group and standard environment group. The present study provided the first evidence for the protective effects of enriched environment on the CNPase positive cells in aged hippocampus.

  11. Low-intensity treadmill exercise and/or bright light promote neurogenesis in adult rat brain

    Institute of Scientific and Technical Information of China (English)

    Sung Jin Kwon; Jeongsook Park; So Yun Park; Kwang Seop Song; Sun Tae Jung; So Bong Jung; Ik Ryeul Park; Wan Sung Choi; Sun Ok Kwon

    2013-01-01

    The hippocampus is a brain region responsible for learning and memory functions. The purpose of this study was to investigate the effects of low-intensity exercise and bright light exposure on neurogenesis and brain-derived neurotrophic factor expression in adult rat hippocampus. Male Sprague-Dawley rats were randomly assigned to control, exercise, light, or exercise + light groups (n = 9 per group). The rats in the exercise group were subjected to treadmill exercise (5 days per week, 30 minutes per day, over a 4-week period), the light group rats were irradiated (5 days per week, 30 minutes per day, 10 000 lx, over a 4-week period), the exercise + light group rats were subjected to treadmill exercise in combination with bright light exposure, and the control group rats remained sedentary over a 4-week period. Compared with the control group, there was a significant increase in neurogenesis in the hippocampal dentate gyrus of rats in the exercise, light, and exercise + light groups. Moreover, the expression level of brain-derived neurotrophic factor in the rat hippocampal dentate gyrus was significantly higher in the exercise group and light group than that in the control group. Interestingly, there was no significant difference in brain-derived neurotrophic factor expression between the control group and exercise + light group. These results indicate that low-intensity treadmill exercise (first 5 minutes at a speed of 2 m/min, second 5 minutes at a speed of 5 m/min, and the last 20 minutes at a speed of 8 m/min) or bright-light exposure therapy induces positive biochemical changes in the brain. In view of these findings, we propose that moderate exercise or exposure to sunlight during childhood can be beneficial for neural development.

  12. Brain edema after intracerebral hemorrhage in rats: The role of inflammation

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    Zhang Xiangjian

    2006-01-01

    Full Text Available Background: Intracerebral hemorrhage (ICH results in secondary brain edema and injury that may lead to death and disability. ICH also causes inflammation. It is unclear whether inflammation contributes to brain edema and neuron injury or functions in repairing the brain tissue. Aims: To understand the effect of inflammation in ICH, we have carried out an investigation on the various aspects and the dynamic changes of inflammation. Settings and Design: An ICH model was generated by injecting 50 ml autologous tail artery blood stereotactically into the right caudate nucleus of 30 rats, which were randomly divided into five ICH groups. Similarly, five Sham control groups were generated by inserting the needle to the right caudate nucleus of rats. Materials and Methods: Rat behavior was evaluated over the time course (6 h, 24 h, 48 h, 72 h and 7 d in each group. The rats were then killed by administering an overdose of pentobarbital. Following the euthanasia, the brain water content, neuronal loss, glia proliferation, inflammatory infiltration and brain morphology of the rats were measured. Additionally, the expression of TNF-a,IL-6, ICAM-1, VEGF, NF-kB, C3 and CR2 was analyzed by immunohistochemistry. Statistical Analysis: The data were analyzed by student′s t test. Results: Rat brain water content increased progressively over the time course and reached its peak at 48h followed ICH. The maximum of inflammatory infiltrate (especially neutrophils and immunopositive cells of TNF-a, IL-6 and NF-kB, were at 48h. The expression of C3 and CR2 reached their peaks at 48-72h, while the expression ICAM-1 and VEGF were at maximum at 72h followed ICH. Conclusions: The results suggested that the inflammatory cytokines, complement system and VEGF may have a function in the development of the brain edema and neuron injury followed ICH.

  13. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug

    OpenAIRE

    Marschallinger, J.; I. Schäffner; B. Klein(Ghent University, Ghent, Belgium); R. Gelfert; F.J. Rivera; S. Illes; L. Grassner; Janssen, M.; P. Rotheneichner; C. Schmuckermair; R. Coras; M. Boccazzi; M. Chishty; F.B. Lagler; M. Renic

    2015-01-01

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood–brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) ...

  14. Caffeine exposure during rat brain development causes memory impairment in a sex selective manner that is offset by caffeine consumption throughout life.

    Science.gov (United States)

    Ardais, Ana Paula; Rocha, Andréia S; Borges, Maurício Felisberto; Fioreze, Gabriela T; Sallaberry, Cássia; Mioranzza, Sabrina; Nunes, Fernanda; Pagnussat, Natália; Botton, Paulo Henrique S; Cunha, Rodrigo A; Porciúncula, Lisiane de Oliveira

    2016-04-15

    Caffeine is the psychostimulant most consumed worldwide. In moderate doses, it affords a beneficial effect in adults and upon aging, but has a deleterious effect during brain development. We now tested if caffeine consumption by rats (0.1, 0.3, 1.0 g/L in the drinking water, only during active cycle and weekdays) during adulthood could revert the potentially negative effects of caffeine during early life. Thus, we compared caffeine intake starting 15 days before mating and lasting either up to weaning (development) or up to adulthood, on behavior and synaptic proteins in male and female rats. Recognition memory was impaired only in female rats receiving caffeine (0.3 and 1.0 g/L) during development, coincident with increased proBDNF and unchanged BDNF levels in the hippocampus. Caffeine in both treatment regimens caused hyperlocomotion only in male rats, whereas anxiety-related behavior was attenuated in both sexes by caffeine (1.0 g/L) throughout life. Both caffeine treatment regimens decreased GFAP (as an astrocyte marker) and SNAP-25 (as a nerve terminals marker) in the hippocampus from male rats. TrkB receptor was decreased in the hippocampus from both sexes and treatment regimens. These findings revealed that caffeine intake during a specific time window of brain development promotes sex-dependent behavioral outcomes related to modification in BDNF signaling. Furthermore, caffeine throughout life can overcome the deleterious effects of caffeine on recognition memory during brain development in female rats. PMID:26774980

  15. Changes of learning and memory ability and brain nicotinic receptors of rat offspring with coal burning fluorosis

    Energy Technology Data Exchange (ETDEWEB)

    Gui, C.Z.; Ran, L.Y.; Li, J.P.; Guan, Z.Z. [Guiyang Medical College, Guiyang (China). Dept. of Pathology

    2010-09-15

    The purpose of the investigation is to reveal the mechanism of the decreased ability of learning and memory induced by coal burning fluorosis. Ten offspring SD rats aged 30 days, who were born from the mothers with chronic coal burning fluorosis, and ten offspring with same age from the normal mothers as controls were selected. Spatial learning and memory of the rats were evaluated by Morris Water Maze test. Cholinesterase activity was detected by photometric method. The expressions of nicotinic acetylcholine receptors (nAChRs) at protein and mRNA levels were detected by Western blotting and Real-time PCR, respectively. The results showed that in the rat offspring exposed to higher fluoride as compared to controls, the learning and memory ability declined; the cholinesterase activities in the brains were inhibited; the protein levels of alpha 3, alpha 4 and alpha 7 nAChR subunits were decreased which showed certain significant correlations with the declined learning and memory ability; and the mRNA levels of alpha 3 and alpha 4 nAChRs were decreased, whereas the alpha 7 mRNA increased. The data indicated that coal burning fluorosis can induce the decreased ability of learning and memory of rat offspring, in which the mechanism might be connected to the changed nAChRs and cholinesterase.

  16. Ovariectomy-induced chronic abdominal hypernociception in rats: Relation with brain oxidative stress

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    Bárbara B. Garrido-Suárez

    2015-12-01

    Full Text Available Context: Ovarian hormone deficiency observed in menopausal women increases the production of reactive oxygen species, which could be implicated in central sensitization subjacent in chronic functional pain syndromes. Aims: To examine the hyperalgesic state induced by ovariectomy in adult rats and its relation to some oxidative stress outcomes. Methods: The female Wistar rats were divided into normal, sham ovariectomized (OVX and OVX groups, which were tested for mechanical and thermal hypernociception during 6 weeks and a single acetic acid-induced test 6 weeks after surgery. Redox biomarkers determinations of superoxide dismutase (SOD enzyme activity, glutathione (GSH and nitrates/nitrites as an indicator of nitric oxide (NO concentrations were determined in the brain and cerebellum of 6 animals of each group. Results: Exclusivity OVX rats developed a robust state of mechanical hypernociception and allodynia in the abdomen, hindlimbs and proximal tail. Besides, thermal pain thresholds (hot plate decreased. That was established 3-4 weeks after OVX and lasted for the 6 weeks of the experiment. Increases in visceral sensitivity were also observed in OVX rats. SOD enzyme activity decreased in OVX rats, which showed major deficit for this enzymatic defense under visceral inflammatory injury. However GSH concentrations were increased in brain of OVX animals that allow the balance during acute inflammation. NO concentrations were raised only in OVX rats exposure to chemical inflammatory injury. Conclusions: OVX in rats provide a useful model, which mimics the functional pain in females that could be related with brain oxidative stress.

  17. Inhibition of tau hyperphosphorylation and beta amyloid production in rat brain by oral administration of atorvastatin

    Institute of Scientific and Technical Information of China (English)

    LU Fen; LI Xu; SUO Ai-qin; ZHANG Jie-wen

    2010-01-01

    Background Alzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia in the elderly. The two hallmark lesions in AD brain are deposition of amyloid plaques and neurofibrillary tangles (NFTs).Hypercholesteremia is one of the risk factors of AD. But its role in the pathogenesis of AD is largely unknown. The aim of this study was to investigate the relationship between hypercholesteremia and tau phosphorylation or β-amyloid (Aβ),and evaluate the effect of atorvastatin on the level of tau phosphorylation and Aβ in the brains of rats fed with high cholesterol diet.Methods Sprague-Dawley (SD) rats were randomly divided into normal diet control group, high cholesterol diet group,and high cholesterol diet plus atorvastatin (Lipitor, 15 mg·kg-1·d-1) treated group. Blood from caudal vein was collected to measure total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL) at the end of the 3th and the 6th months by an enzymatic method. The animals were sacrificed 6 months later and brains were removed. All left brain hemispheres were fixed for immunohistochemistry. Hippocampus and cerebral cortex were separated from right hemispheres and homogenized separately. Tau phosphorylation and Aβ in the brain tissue were determined by Western blotting (using antibodies PHF-1 and Tau-1) and anti-Aβ40/anti-Aβ42, respectively.Results We found that high cholesterol diet led to hypercholesteremia of rats as well as hyperphosphorylation of tau and increased Aβ level in the brains. Treatment of the high cholesterol diet fed rats with atorvastatin prevented the changes of both tau phosphorylation and Aβ level induced by high cholesterol diet.Conclusions Hypercholesteremia could induce tau hyperphosphorylation and Aβ production in rat brain. Atorvastatin could inhibit tau hyperphosphorylation and decrease Aβ generation. It may play a protective role in the patho-process of hypercholesteremia

  18. Blueberries and strawberries activate neuronal housekeeping in critical brain regions of stress-induced young rats

    Science.gov (United States)

    Dysfunctional autophagy, where accumulation of damaged or complex cellular components in neurons in response to sublethal cell stress has been implicated in an array of brain disorders. This phenomenon plays a pivotal role in aging, because of the increased vulnerability of the aging brain to incre...

  19. Identification of new therapeutic targets by genome-wide analysis of gene expression in the ipsilateral cortex of aged rats after stroke.

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    Ana-Maria Buga

    Full Text Available BACKGROUND: Because most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions. METHODOLOGY/PRINCIPAL FINDINGS: We employed the Affymetrix platform to analyze the whole-gene transcriptome following temporary ligation of the middle cerebral artery in aged and young rats. The correspondence, heat map, and dendrogram analyses independently suggest a differential, age-group-specific behaviour of major gene clusters after stroke. Overall, the pattern of gene expression strongly suggests that the response of the aged rat brain is qualitatively rather than quantitatively different from the young, i.e. the total number of regulated genes is comparable in the two age groups, but the aged rats had great difficulty in mounting a timely response to stroke. Our study indicates that four genes related to neuropathic syndrome, stress, anxiety disorders and depression (Acvr1c, Cort, Htr2b and Pnoc may have impaired response to stroke in aged rats. New therapeutic options in aged rats may also include Calcrl, Cyp11b1, Prcp, Cebpa, Cfd, Gpnmb, Fcgr2b, Fcgr3a, Tnfrsf26, Adam 17 and Mmp14. An unexpected target is the enzyme 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 in aged rats, a key enzyme in the cholesterol synthesis pathway. Post-stroke axonal growth was compromised in both age groups. CONCLUSION/SIGNIFICANCE: We suggest that a multi-stage, multimodal treatment in aged animals may be more likely to produce positive results. Such a therapeutic approach should be focused on tissue restoration but should also address other aspects of patient post-stroke therapy such as neuropathic syndrome, stress, anxiety disorders, depression, neurotransmission and blood pressure.

  20. Green tea polyphenols supplementation improves bone microstructure in orchidectomized middle-Aged rats

    Science.gov (United States)

    Our recent study shows that green tea polyphenols (GTP) attenuate trabecular bone loss in ovariectomized middle-aged female rats. To investigate whether GTP prevents bone loss in male rats, 40 rats with and without oriectomy (ORX) were assigned to 4 groups in a 2 (sham vs. ORX)× 2 (no GTP and 0.5% G...

  1. Relationship between orientation to a blast and pressure wave propagation inside the rat brain.

    Science.gov (United States)

    Chavko, Mikulas; Watanabe, Tomas; Adeeb, Saleena; Lankasky, Jason; Ahlers, Stephen T; McCarron, Richard M

    2011-01-30

    Exposure to a blast wave generated during an explosion may result in brain damage and related neurological impairments. Several mechanisms by which the primary blast wave can damage the brain have been proposed, including: (1) a direct effect of the shock wave on the brain causing tissue damage by skull flexure and propagation of stress and shear forces; and (2) an indirect transfer of kinetic energy from the blast, through large blood vessels and cerebrospinal fluid (CSF), to the central nervous system. To address a basic question related to the mechanisms of blast brain injury, pressure was measured inside the brains of rats exposed to a low level of blast (~35kPa), while positioned in three different orientations with respect to the primary blast wave; head facing blast, right side exposed to blast and head facing away from blast. Data show different patterns and durations of the pressure traces inside the brain, depending on the rat orientation to blast. Frontal exposures (head facing blast) resulted in pressure traces of higher amplitude and longer duration, suggesting direct transmission and reflection of the pressure inside the brain (dynamic pressure transfer). The pattern of the pressure wave inside the brain in the head facing away from blast exposures assumes contribution of the static pressure, similar to hydrodynamic pressure to the pressure wave inside the brain. PMID:21129403

  2. Effect of borneol and electroacupuncture on the distribution of hyperforin in the rat brain

    Institute of Scientific and Technical Information of China (English)

    Bin Yu; Ming Ruan; Yong Sun; Xiaobing Cui; Yun Yu; Lingling Wang; Taihui Fang

    2011-01-01

    Hyperforin is an antidepressant drug that has unstable therapeutic effects, due to its poor ability to cross the blood-brain barrier. Borneol and electroacupuncture have both been found to increase the permeability of the blood-brain barrier. As such, the current study examined the distribution of hyperforin in the rat brain, and the effects on the brain distribution of hyperforin of borneol alone (orally administered), and borneol combined with electroacupuncture treatment. High-performance liquid chromatography technology and pharmacokinetic analysis revealed that treatment with borneol alone (300, 600 mg/kg) increased peak concentration and the area under the curve for hyperforin in the brain. In addition, the bioavailability of hyperforin in rat brain increased by 42.7%. However, increasing the dose of borneol dose did not appear to increase the distribution of hyperforin in the brain. Importantly, applying electroacupuncture at Baihui (GV 20) or Yamen (GV 15) appeared to enhance the brain-delivery effects of borneol, although this effect was weak. Overall, our results indicated that borneol alone or combined with electroacupuncture can provide promising strategies for brain-targeted delivery in central nervous system therapy.

  3. Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats.

    Science.gov (United States)

    Hays, Seth A; Ruiz, Andrea; Bethea, Thelma; Khodaparast, Navid; Carmel, Jason B; Rennaker, Robert L; Kilgard, Michael P

    2016-07-01

    Advanced age is associated with a higher incidence of stroke and worse functional outcomes. Vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a potential method to improve recovery after brain injury but to date has only been evaluated in young rats. Here, we evaluated whether VNS paired with rehabilitative training would improve recovery of forelimb function after ischemic lesion of the motor cortex in rats 18 months of age. Rats were trained to perform the isometric pull task, an automated, quantitative measure of volitional forelimb strength. Once proficient, rats received an ischemic lesion of the motor cortex and underwent rehabilitative training paired with VNS for 6 weeks. VNS paired with rehabilitative training significantly enhances recovery of forelimb function after lesion. Rehabilitative training without VNS results in a 34% ± 19% recovery, whereas VNS paired with rehabilitative training yields a 98% ± 8% recovery of prelesion of forelimb function. VNS does not significantly reduce lesion size. These findings demonstrate that VNS paired with rehabilitative training enhances motor recovery in aged subjects in a model of stroke and may suggest that VNS therapy may effectively translate to elderly stroke patients. PMID:27255820

  4. Features of microelement maintenance in rat's brain tissues at experimental hypoxia of different degree.

    Directory of Open Access Journals (Sweden)

    Tarasova I.V.

    2011-01-01

    Full Text Available Features of microelement maintenance (iron, zinc, copper, manganese, and cobalt, conditionally toxic chrome and toxic lead were studied in newborn rat's brain tissues at experimental hypoxia of different degree. Tissues of newborn rat’s brain are characterized by high level of saturation and considerable dynamism of microelement maintenance. Till the end of the first week of life, the maintenance of these microelements decreases in 1,5 – 10 times. The level of the toxic lead decreases more than in 2,5 times. The hypoxia of easy degree of newborn rats invokes reduction cobalt level 3 times, iron level 2 times, manganese – on 27,65 %, chrome – on 25,84%, zinc – on 16,43%. It means that considerable deficiency and disbalance of microelement maintenance rat's brain tissues. The heavy degree of hypoxia is characterized by further increase of deficiency and disbalance of microelements.

  5. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Omar Ortiz-Avila

    2015-01-01

    Full Text Available Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats. Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential ΔΨm, besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

  6. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats.

    Science.gov (United States)

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨ m ), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

  7. Effect of pineapple peel extract on total phospholipids and lipid peroxidation in brain tissues of rats

    Institute of Scientific and Technical Information of China (English)

    Erukainure OL; Ajiboye JA; Adejobi RO; Okafor OY; Kosoko SB; Owolabi FO

    2011-01-01

    Objective:To investigate the ability of the methanolic extract of pineapple peel to attenuate alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues. Methods:Oxidative stress was induced by oral administration of ethanol (20%w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Brain tissues were assayed for total phospholipid (TP) content and malondialdehyde (MDA). Results:Administration of alcohol significantly caused a reduction in TP content. Treatment with pineapple peel extract significantly increased the TP content. Significant high levels of MDA was observed in alcohol-fed rats, treatment with pineapple peel extract significantly reduced the MDA levels. Conclusions:Results obtained from this study indicates that pineapple peel extract protects against alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues.

  8. Glucocorticoids modulate BDNF mRNA expression in the rat hippocampus after traumatic brain injury.

    Science.gov (United States)

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2000-10-20

    Brain-derived neurotrophic factor (BDNF) expression in rat hippocampus is increased after experimental traumatic brain injury (TBI) and may be neuroprotective. Glucocorticoids are important regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) on the expression of BDNF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury (FPI) and in situ hybridization to evaluate the expression of BDNF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomized rats (with or without corticosterone replacement). FPI and ADX independently increased expression of BDNF mRNA. In animals undergoing FPI, prior ADX caused further elevation of BDNF mRNA and this upregulation was prevented by corticosterone replacement in ADX rats. These findings suggest that glucocorticoids are involved in the modulation of the BDNF mRNA response to TBI.

  9. Anti-epileptic effects of neuropeptide Y gene transfection into the rat brain

    Institute of Scientific and Technical Information of China (English)

    Changzheng Dong; Wenqing Zhao; Wenling Li; Peiyuan Lv; Xiufang Dong

    2013-01-01

    Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carrying the neuropeptide Y gene was transfected into brain tissue of rats with kainic acid-induced epilepsy through stereotactic methods. Following these transfections, we verified overexpression of the neuropeptide Y gene in the epileptic brain. Electroencephalograms showed that seizure severity was significantly inhibited and seizure latency was significantly prolonged up to 4 weeks after gene transfection. Moreover, quantitative fluorescent PCR and western blot assays revealed that the mRNA and protein expression of the N-methyl-D-aspartate receptor subunits NR1, NR2A, and NR2B was inhibited in the hippocampus of epileptic rats. These findings indicate that neuropeptide Y may inhibit seizures via down-regulation of the functional expression of N-methyl-D-aspartate receptors.

  10. Effects of anesthesia on [11C]raclopride binding in the rat brain

    DEFF Research Database (Denmark)

    Alstrup, Aage Kristian Olsen; Simonsen, Mette; Møller, Arne;

    Background Very often rats are anesthetized prior to micro positron emission tomography (microPET) brain imaging in order to prevent head movements. Anesthesia can be administered by inhalation agents, such as isoflurane, or injection mixtures, such as fentanyl-fluanisone-midazolam. Unfortunately......, anesthesia affects a variety of physiological variables, including in the brain. Aim The aim of this study was to compare the effects of inhalation and injection anesthesia on the binding potential of the dopaminergic D2/3 tracer [11C]raclopride used for PET brain imaging in human and animal studies....... Materials & Methods Nine male Lew/Mol rats were assigned to either inhalation (isoflurane; N=4) or injection (fentanyl-fluanisone-midazolam; N=5) anesthesia. Catheters were surgically placed in femoral arteries and veins for blood sampling and tracer injection. After a short attenuation scan, the rats were...

  11. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats.

    Science.gov (United States)

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨ m ), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress. PMID:26180820

  12. Effect of mealing on plasma and brain amino acid, and brain monoamine in rats after oral aspartame.

    Science.gov (United States)

    Torii, K; Mimura, T; Takasaki, Y; Ichimura, M

    1986-01-01

    Aspartame (APM; L-aspartyl-L-phenylalanine methyl ester) was investigated for its ability to alter brain amino acids and monoamines in overnight fasted rats allowed to consume commercial diets for 60 minutes. In addition, the effects of mealing on the changes in plasma and brain amino acids and brain monoamines induced by glucose and/or insulin, and known pharmacologically active compounds, were studied. The consumption of the commercial chow largely prevented changes in blood glucose and amino acids, and brain amino acids and the monoamines dopamine, norepinephrine and serotonin that might be expected to occur following glucose with or without insulin. Feeding failed to prevent changes in the above parameters when 5-hydroxy-tryptophan, p-chlorophenylalanine and reserpine were administered. The oral administration of up to 250 mg/kg BW APM with water or glucose followed by free feeding failed to alter brain monoamines. These studies demonstrate the potent ability of food to normalize biochemical parameters in blood and brain that otherwise might occur, and clearly show the lack of effect on brain monoamine levels of abuse doses of APM when administered with food. PMID:2940610

  13. Linking pathways in the developing and aging brain with neurodegeneration

    NARCIS (Netherlands)

    G.G. Kovacs; H. Adle-Biassett; I. Milenkovic; S. Cipriani; J. van Scheppingen; E. Aronica

    2014-01-01

    The molecular and cellular mechanisms, which coordinate the critical stages of brain development to reach a normal structural organization with appropriate networks, are progressively being elucidated. Experimental and clinical studies provide evidence of the occurrence of developmental alterations

  14. Modulation of intestinal microbiota by the probiotic VSL#3 resets brain gene expression and ameliorates the age-related deficit in LTP.

    Directory of Open Access Journals (Sweden)

    Eleonora Distrutti

    Full Text Available The intestinal microbiota is increasingly recognized as a complex signaling network that impacts on many systems beyond the enteric system modulating, among others, cognitive functions including learning, memory and decision-making processes. This has led to the concept of a microbiota-driven gut-brain axis, reflecting a bidirectional interaction between the central nervous system and the intestine. A deficit in synaptic plasticity is one of the many changes that occurs with age. Specifically, the archetypal model of plasticity, long-term potentiation (LTP, is reduced in hippocampus of middle-aged and aged rats. Because the intestinal microbiota might change with age, we have investigated whether the age-related deficit in LTP might be attenuated by changing the composition of intestinal microbiota with VSL#3, a probiotic mixture comprising 8 Gram-positive bacterial strains. Here, we report that treatment of aged rats with VSL#3 induced a robust change in the composition of intestinal microbiota with an increase in the abundance of Actinobacteria and Bacterioidetes, which was reduced in control-treated aged rats. VSL#3 administration modulated the expression of a large group of genes in brain tissue as assessed by whole gene expression, with evidence of a change in genes that impact on inflammatory and neuronal plasticity processes. The age-related deficit in LTP was attenuated in VSL#3-treated aged rats and this was accompanied by a modest decrease in markers of microglial activation and an increase in expression of BDNF and synapsin. The data support the notion that intestinal microbiota can be manipulated to positively impact on neuronal function.

  15. EFFECT OF GINKGO BILOBA EXTRACT ON BRAIN EDEMA AFTER SUBARACHNOID HEMORRHAGE IN RATS

    Institute of Scientific and Technical Information of China (English)

    孙保亮; 夏作理; 杨明峰; 邱平明

    2001-01-01

    @@ The aim of this study was to investigate the protectiveeffect of Ginkgo biloba extract (EGb) on brain edemaafter subarachnoid hemorrhage . Eighty male and femaleWistar rats, weighing 300~ 350g, were used in the ex-periment. Animals were divided into pure SAH group andEGb-treated group. Dynamic changes of regional cerebralblood flow (rCBF) were detected in eight rats from eachgroup. Brain water and electrolytes contents at differenttime points were detected in thirty-two rats from eachgroup (eight rats at each time point from each group) .EGb. provided by Pizhou Pharmaceutical Factory(Xuzhou, Jiangsu, China), was injected intraperi-toneally 30 minutes before operation and repeated withsingle dose of 15mg/kg .every 6 hours.

  16. Transplanted bone marrow stromal cells improve cognitive dysfunction due to aging hypoperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    HUANG Jing; YIN Shao-jun; CHEN Yu-juan; BIAN Wei-hong; YU Jing; ZHAO Yu-wu; LIU Xue-yuan

    2010-01-01

    Background Aging is an important risk factor for vascular dementia, and D-galactose (D-gal) injection can simulate the pathology of aging. Two-vessel occlusion of common carotid arteries (2VO) is the most popular model for vascular dementia. This study was aimed to investigate the possibility of D-gal injection plus 2VO simulating cognitive impairment of aging vascular dementia; and whether transplanted bone marrow stromal cells (BMSCs) can improve the cognitive function induced by D-gal injection plus 2VO.Methods Totally 30 male Sprague-Dawley rats were divided into 5 groups equivalently: control group, D-gal group,D-gal+2VO group, D-gal+2VO+saline water group, and D-gal+2VO+BMSCs group. Aging hypoperfusion rats were created by subcutaneous injection of D-gal and occlusion of two common carotid arteries. BMSCs or saline water was stereotactically transplanted into the subventricular zone as treatment vehicles at 24 hours post operation. Two-way repeat analysis of variance (ANOVA) was used for significance analysis of 5 groups at 6 weeks post transplantation;moreover, Tamhane's test (equal variance not assumed) and least significant difference (LSD) test (equal variance assumed) were used for pairwise comparison in Morris water maze (MWM).Results Transplanted BMSCs distributed around the lateral ventricles and acquired the phenotypes of neurons and astrocytes. In terms of swimming path distance and escape latency in MWM, D-gal+2VO+BMSC group showed significant improvement than the D-gal+2VO group but was still obviously worse than the control group (both P <0.05).There was no significant difference in swimming speed for all 5 groups.Conclusions D-gal plus 2VO induces cognitive dysfunction. The engrafted BMSCs exhibit the beneficial effect on cognitive function via promotion interactively with host brain.

  17. Neuroprotective effects of consuming bovine colostrum after focal brain ischemia/reperfusion injury in rat model

    Science.gov (United States)

    Choi, Han Sung; Ko, Young Gwan; Lee, Jong Seok; Kwon, Oh Young; Kim, Sun-Kyu; Cheong, Chul; Jang, Ki-Hyo

    2010-01-01

    To investigate the neuroprotective effects of bovine colostrums (BC), we evaluate the ability of consuming BC after focal brain ischemia/reperfusion injury rat model to reduce serum cytokine levels and infarct volume, and improve neurological outcome. Sprague-Dawley rats were randomly divided into 4 groups; one sham operation and three experimental groups. In the experimental groups, MCA occlusion (2 h) and subsequent reperfusion (O/R) were induced with regional cerebral blood flow monitoring. One hour after MCAO/R and once daily during the experiment, the experimental group received BC while the other groups received 0.9% saline or low fat milk (LFM) orally. Seven days later, serum pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) and anti-inflammatory cytokine (IL-10) levels were assessed. Also, the infarct volume was assessed by using a computerized image analysis system. Behavioral function was also assessed using a modified neurologic severity score and corner turn test during the experiment. Rats receiving BC after focal brain I/R showed a significant reduction (-26%/-22%) in infarct volume compared to LFM/saline rats, respectively (P < 0.05). Serum IL-1β, IL-6, and TNF-α levels were decreased significantly in rats receiving BC compared to LFM/saline rats (P < 0.05). In behavioral tests, daily BC intake showed consistent and significant improvement of neurological deficits for 7 days after MCAO/R. BC ingestion after focal brain ischemia/reperfusion injury may prevent brain injury by reducing serum pro-inflammatory cytokine levels and brain infarct volume in a rat model. PMID:20607064

  18. Effects of Graded Hypothermia on Hypoxic-ischemic Brain Damage in the Neonatal Rat

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan Xia; Yi-xin Xia

    2011-01-01

    Objective To investigate the effect of graded hypothermia on neuropathologic alteratiors of neonatal rat brain after exposed to hypoxic-ischemic insult at 37℃, 33℃, 31℃, and 28℃, respectively, and to observe the effect of hypothermia on 72-kDa heat shock protein (HSP72) expression after hypoxic-ischemic insult. Methods Seven days old Wistar rats were subjected to unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 2 hours at 37℃, 33℃, 31℃, and 28℃, respectively. The brain temperature was monitored indirectly by inserting a mini-thermocouple probe into the temporal muscle during hypoxia. After hypoxia-ischemia their mortality was assessed. Neuronal damage was assessed with HE staining 72 hours after hypoxia. HSP72 expression at 0.5, 24, and 72 hours of recovery was immunohistochemically assessed using a monoclonal antibody to HSP72. Results Hypoxia-ischemia caused 10.5% (2/19) of mortality in rat of 37℃ group, but no death occurred in 33℃, 31℃ or 28℃ groups. HE staining showed neuropathologic damage was extensive in rats exposed to hypoxia-ischemia at 37℃ (more than 80.0%). The incidence of severe brain damage was significantly decreased in 33℃ (53.3%) and 31℃ groups (44.4%), and no histologic injury was seen in the 28℃ group of rats. Expression of HSP72 was manifest and persistent in the rat brain of 37℃ group, but minimum in the rat brain of 28℃ group. Conclusion Mild and moderate hypothermia might prevent cerebral visible neuropathologic damage associated with hypoxic-ischemic injury by decreasing stress response.

  19. Protective effect of DL-3-n-Butylphthalide on radiation injury of rat brain tissue

    International Nuclear Information System (INIS)

    Objective: To investigate the protective effect and its mechanism of DL-3-n-Butylphthalide on the brain damage in rats following whole brain irradiation. Methods: A total of 120 male Sprague Dawley rats were randomly divided into sham-irradiation group, irradiation group and DL-3-n-Butylphthalide group. The model of whole-brain irradiation was established by exposing rat brain to 4 MeV X-rays with a single-dose of 10 Gy. The rats were intraperitoneally injected with DL-3-n-Butylphthalide at the dosages of 0.3, 1.0, and 3.0 mg/kg once a day. The contents of malondialdehyde and super oxide dismutase activity were measured, while the expressions of apoptosis-associated genes and the ultrastructural changes in hippocampus were examined by immunohistochemistry staining and electron microscope, respectively. Results: After irradiation, the content of malondialdehyde and the expression of apoptosis gene bax in rat brain tissue increased while the activity of super oxide dismutase (SOD) and the expression of anti-apoptosis gene bcl-2 decreased. Apoptosis was also observed in the neurons of hippocampus CA1. Compared with irradiation group, the content of malondialdehyde and the expression of bax gene in the DL-3-n-Butylphthalide group wen significantly reduced (t=-3.89 - -1.96, 2.72-3.48, P<0.05), while the activity of SOD and bcl-2 gene were significantly elevated (t=2.94-3.76, -3.18 - -2.08, P<0.05), and the injury degree of neuron structure in the DL-3-n-Butylphthalide group was slighter than that in the irradiation group. Conclusions: DL-3-n-Butylphthalide executes protective effects in a dose-dependent manner against the radiation injury in rats brain by reducing the induction of malondialdehyde, raising the activity of SOD and inhibiting the generation of apoptosis. (authors)

  20. White matter hyperintensities and imaging patterns of brain ageing in the general population.

    Science.gov (United States)

    Habes, Mohamad; Erus, Guray; Toledo, Jon B; Zhang, Tianhao; Bryan, Nick; Launer, Lenore J; Rosseel, Yves; Janowitz, Deborah; Doshi, Jimit; Van der Auwera, Sandra; von Sarnowski, Bettina; Hegenscheid, Katrin; Hosten, Norbert; Homuth, Georg; Völzke, Henry; Schminke, Ulf; Hoffmann, Wolfgang; Grabe, Hans J; Davatzikos, Christos

    2016-04-01

    White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P brain atrophy found in beyond-normal brain ageing in the general population. White matter hyperintensities also contribute to brain atrophy patterns in regions related to Alzheimer's disease dementia, in agreement with their known additive role to the likelihood of dementia. Preventive strategies reducing the odds to develop cardiovascular disease and white matter hyperintensities could decrease the incidence or delay the onset of dementia.

  1. Parameterization of the Age-Dependent Whole Brain Apparent Diffusion Coefficient Histogram

    Directory of Open Access Journals (Sweden)

    Uwe Klose

    2015-01-01

    Full Text Available Purpose. The distribution of apparent diffusion coefficient (ADC values in the brain can be used to characterize age effects and pathological changes of the brain tissue. The aim of this study was the parameterization of the whole brain ADC histogram by an advanced model with influence of age considered. Methods. Whole brain ADC histograms were calculated for all data and for seven age groups between 10 and 80 years. Modeling of the histograms was performed for two parts of the histogram separately: the brain tissue part was modeled by two Gaussian curves, while the remaining part was fitted by the sum of a Gaussian curve, a biexponential decay, and a straight line. Results. A consistent fitting of the histograms of all age groups was possible with the proposed model. Conclusions. This study confirms the strong dependence of the whole brain ADC histograms on the age of the examined subjects. The proposed model can be used to characterize changes of the whole brain ADC histogram in certain diseases under consideration of age effects.

  2. The levels of soluble versus insoluble brain Abeta distinguish Alzheimer's disease from normal and pathologic aging.

    Science.gov (United States)

    Wang, J; Dickson, D W; Trojanowski, J Q; Lee, V M

    1999-08-01

    The abundance and solubility of Abeta peptides are critical determinants of amyloidosis in Alzheimer's disease (AD). Hence, we compared levels of total soluble, insoluble, and total Abeta1-40 and Abeta1-42 in AD brains with those in age-matched normal and pathologic aging brains using a sandwich enzyme-linked immunosorbent assay (ELISA). Since the measurement of Abeta1-40 and Abeta1-42 depends critically on the specificity of the monoclonal antibodies used in the sandwich ELISA, we first demonstrated that each assay is specific for Abeta1-40 or Abeta1-42 and the levels of these peptides are not affected by the amyloid precursor protein in the brain extracts. Thus, this sandwich ELISA enabled us to show that the average levels of total cortical soluble and insoluble Abeta1-40 and Abeta1-42 were highest in AD, lowest in normal aging, and intermediate in pathologic aging. Remarkably, the average levels of insoluble Abeta1-40 were increased 20-fold while the average levels of insoluble Abeta1-42 were increased only 2-fold in the AD brains compared to pathologic aging brains. Further, the soluble pools of Abeta1-40 and Abeta1-42 were the largest fractions of total Abeta in the normal brain (i.e., 50 and 23%, respectively), but they were the smallest in the AD brain (i.e., 2.7 and 0.7%, respectively) and intermediate (i.e., 8 and 0.8%, respectively) in pathologic aging brains. Thus, our data suggest that pathologic aging is a transition state between normal aging and AD. More importantly, our findings imply that a progressive shift of brain Abeta1-40 and Abeta1-42 from soluble to insoluble pools and a profound increase in the levels of insoluble Abeta1-40 plays mechanistic roles in the onset and/or progression of AD.

  3. Treatment of brain tumours with electroporation and bleomycin in an in vivo rat model

    OpenAIRE

    Ljungvall, Magnus; Salford, Leif; Persson, Bertil R

    2013-01-01

    The purpose of the study was to examine the possibilities of prolonging the life of rats with brain tumours using electroporation only while conducting impedance scans to evaluate the rate of electroporation. During the experiments, the treated rats in the first batch had tumors grow for 14 days and were then given electroporation with 8 + 8 exponential pulses at 800 v/cm, and 15 micro-F. Three of the animals given electroporation and bleomycin and one of the animals given e...

  4. Effects of delayed treatment with nebracetam on neurotransmitters in brain regions after microsphere embolism in rats

    OpenAIRE

    Takeo, Satoshi; Hayashi, Hideki; Miyake, Keiko; Takagi, Kaori; Tadokoro, Mina; Takagi, Norio; Oshikawa, Sayuri

    1997-01-01

    The effects of delayed treatment with nebracetam, a novel nootropic drug, on neurotransmitters of brain regions were examined in rats with microsphere embolism-induced cerebral ischaemia.Cerebral ischaemia was induced by administration of 900 microspheres (48 μm) into the internal carotid artery. The rats with stroke-like symptoms were treated p.o. with 30 mg kg−1 nebracetam twice daily. The levels of acetylcholine, dopamine, noradrenaline, 5-hydroxytryptamine (5-HT) and their metabolites in ...

  5. Intracerebral lipopolysaccharide induces neuroinflammatory change and augmented brain injury in growth-restricted neonatal rats

    OpenAIRE

    Campbell, Leigh R.; Pang, Yi; Ojeda, Norma B.; Zheng, Baoying; Rhodes, Philip G.; Alexander, Barbara T.

    2012-01-01

    Introduction Intrauterine growth-restriction (IUGR) alters fetal development and is associated with neurodevelopmental abnormalities. We hypothesized that growth-restriction from reduced intrauterine perfusion would predispose neonatal rats to subsequent inflammatory brain injury. Methods In the current study, IUGR was achieved by induced placental insufficiency in pregnant rats at 14 days of gestation. IUGR offspring and sham-operated control pups were subsequently injected with intracerebra...

  6. Vascular wall dysfunction in JCR:LA-cp rats: effects of age and insulin resistance.

    Science.gov (United States)

    O'brien, S F; Russell, J C; Davidge, S T

    1999-11-01

    We tested the hypothesis that aging and insulin resistance interact to increase vascular dysfunction by comparing the function of isolated mesenteric resistance arteries in obese, insulin-resistant JCR:LA-cp rats and lean, insulin-sensitive rats of the same strain at 3, 6, 9, and 12 mo of age. The peak constrictor responses to norepinephrine, phenylephrine, and high potassium were elevated in arteries from obese rats. Responses to these agents increased with age in both obese and lean rats. An eicosanoid constrictor contributed substantially to vasoconstriction in the arteries from both lean and obese animals. Inhibition of nitric oxide synthase increased the vasoconstrictor response to norepinephrine in both obese and lean rats. This effect increased with age in lean rats only. Vascular relaxation in response to acetylcholine and sodium nitroprusside was impaired in the obese rats and did not alter with age. The results suggest that obese JCR:LA-cp rats have enhanced maximal constriction, which originates in the arterial smooth muscle and increases with age. There is evidence that the ability of the arteries to compensate for the enhanced contractility is impaired in obese rats, particularly with advanced age.

  7. Gender-specific impact of personal health parameters on individual brain aging in cognitively unimpaired elderly subjects

    Directory of Open Access Journals (Sweden)

    Katja eFranke

    2014-05-01

    Full Text Available Aging alters brain structure and function. Personal health markers and modifiable lifestyle factors are related to individual brain aging as well as to the risk of developing Alzheimer’s disease (AD. This study uses a novel magnetic resonance imaging (MRI-based biomarker to assess the effects of 17 health markers on individual brain aging in cognitively unimpaired elderly subjects. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE score indicates accelerated atrophy and is considered a risk factor for developing AD. Within this cross-sectional, multi-center study 228 cognitively unimpaired elderly subjects (118 males completed an MRI at 1.5T, physiological and blood parameter assessments. The multivariate regression model combining all measured parameters was capable of explaining 39% of BrainAGE variance in males (p < 0.001 and 32% in females (p < 0.01. Furthermore, markers of the metabolic syndrome as well as markers of liver and kidney functions were profoundly related to BrainAGE scores in males (p < 0.05. In females, markers of liver and kidney functions as well as supply of vitamin B12 were significantly related to BrainAGE (p < 0.05. In conclusion, in cognitively unimpaired elderly subjects several clinical markers of poor health were associated with subtle structural changes in the brain that reflect accelerated aging, whereas protective effects on brain aging were observed for markers of good health. Additionally, the relations between individual brain aging and miscellaneous health markers show gender-specific patterns. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of subtly abnormal patterns of brain aging probably preceding cognitive decline and development of AD.

  8. Salvia officinalis l. (sage) Ameliorates Radiation-Induced Oxidative Brain Damage In Rats

    International Nuclear Information System (INIS)

    The present study was designed to investigate the oxidative stress and the role of antioxidant system in the management of gamma irradiation induced whole brain damage in rats . Also, to elucidate the potential role of Salvia officinalis (sage) in alleviating such negative effects. Rats were subjected to gamma radiation (6 Gy). Sage extract was daily given to rats during 14 days before starting irradiation and continued after radiation exposure for another 14 days. The results revealed that the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC) and nitric oxide (NO) content were significantly increased, while the activities of superoxide dismutase (SOD) and catalase (CAT) as well as the reduced glutathione (GSH) content were significantly decreased in the brain homogenate of irradiated rats. Additionally, brain acetylcholinesterase (AChE) as well as alkaline phosphatase (ALP), acid phosphatase (ACP) and lactate dehydrogenase (LDH) activities were significantly increased. On the other hand, the results showed that, administration of sage extract to rats was able to ameliorate the mentioned parameters and the values returned close to the normal ones. It could be concluded that sage extract, by its antioxidant constituents, could modulate radiation induced oxidative stress and enzyme activities in the brain.

  9. Element distribution in the brain sections of rats measured by synchrotron radiation X-ray fluorescence

    Science.gov (United States)

    Liu, N. Q.; Zhang, F.; Wang, X. F.; Zhang, Z. Y.; Chai, Z. F.; Huang, Y. Y.; He, W.; Zhao, X. Q.; Zuo, A. J.; Yang, R.

    2004-02-01

    The concentration of trace elements in brain sections was measured by synchrotron radiation X-ray fluorescence. The relative concentration was calculated by means of the normalization of Compton scattering intensity approximately 22 keV, after the normalization for collecting time of X-ray spectrum and the counting of the ion chamber, and subtracting the contribution of the polycarbonate film for supporting sample. Furthermore, the statistical evaluation of the element distribution in various regions of the brain sections of the 20-day-old rats was tested. For investigating the distribution of elements in the brain of iodine deficient rats, Wistar rats were fed with iodine deficient diet and deionized water (ID group). The rats were fed the same iodine deficient diet, but drank KIO 3 solution as control (CT group). The results showed that the contents of calcium (Ca) in thalamus (TH) and copper (Cu) and iron (Fe) in cerebral cortex (CX) of ID rats were significantly lower than that of control rats, while the contents of phosphor (P), sulfur (S), potassium (K), rubidium (Rb), bromine (Br), chlorine (Cl), zinc (Zn), Ca and Cu of ID in hippocampus (H) and the contents of Br, Cl, Zn and Ca in cerebral cortex of ID rats were significantly higher. Especially, the difference of Br, Cl, Zn and Ca in H between ID and CT was more significant. The contents of all elements measured in H were higher than (or equal to) CX and/or TH for both groups, except low Cl of the control rats. Furthermore Zn and Cu contents along the hippocampal fissure in both groups were 1.5 ( Ptimes higher than in hippocampus, respectively. Considering the results of cluster analysis our study shows that the marked alterations in the spatial distribution of Zn and Ca of ID rats brain during brain development stages. In addition, the effect of the perfusion with 0.9% NaCl solution before taking brain on the distribution of elements in the brain sections was observed and discussed.

  10. The Impact of MicroRNAs on Brain Aging and Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Stephan P. Persengiev

    2012-01-01

    Full Text Available The molecular instructions that govern gene expression regulation are encoded in the genome and ultimately determine the morphology and functional specifications of the human brain. As a consequence, changes in gene expression levels might be directly related to the functional decline associated with brain aging. Small noncoding RNAs, including miRNAs, comprise a group of regulatory molecules that modulate the expression of hundred of genes which play important roles in brain metabolism. Recent comparative studies in humans and nonhuman primates revealed that miRNAs regulate multiple pathways and interconnected signaling cascades that are the basis for the cognitive decline and neurodegenerative disorders during aging. Identifying the roles of miRNAs and their target genes in model organisms combined with system-level studies of the brain would provide more comprehensive understanding of the molecular basis of brain deterioration during the aging process.

  11. Diet and Age Interactions with Regards to Cholesterol Regulation and Brain Pathogenesis

    Directory of Open Access Journals (Sweden)

    Romina M. Uranga

    2010-01-01

    Full Text Available Cholesterol is an essential molecule for brain homeostasis; yet, hypercholesterolemia and its numerous complications are believed to play a role in promoting multiple aspects of brain pathogenesis. An ever increasing number of individuals in modern Western Society are regularly consuming diets high in fat which promote the development of hypercholesterolemia. Additionally, modern societies are becoming increasingly aged, causing a collision between increased hypercholesterolemia and increased aging, which will likely lead to the development of increased pathological conditions due to hypercholesterolemia, thereby promoting deleterious neurochemical and behavioral changes in the brain. Lastly, while beneficial in controlling cholesterol levels, the long-term use of statins itself may potentially promote adverse effects on brain homeostasis, although specifics on this remain largely unknown. This review will focus on linking the current understanding of diet-induced hypercholesterolemia (as well as statin use to the development of oxidative stress, neurochemical alterations, and cognitive disturbances in the aging brain.

  12. Accumulation of N-acyl-ethanolamine phospholipids in rat brains during post-decapitative ischemia

    DEFF Research Database (Denmark)

    Moesgaard, B.; Hansen, Harald S.; Jaroszewski, J.W.

    1999-01-01

    Phosphorus-31 nuclear magnetic resonance (P NMR) spectroscopy has been used to study accumulation of N-acyl-ethanolamine phospholipids in rat brains during post-decapitative ischemia. Lipids were extracted from rat brain homogenates and the extracts were thoroughly washed with aq. potassium......-phospho(N-acyl)-ethanolamine (NAPE(PLAS)), respectively, by spiking with authentic materials. Additionally, the identification was verified by thin-layer chromatography, which also showed the accumulation of N-acyl-ethanolamine phospholipids. The use of K-EDTA instead of the commonly used Cs...

  13. Testosterone does not influence opiate binding sites in the male rat brain.

    Science.gov (United States)

    Cicero, T J; Newman, K S; Meyer, E R

    1983-09-26

    It has been reported previously that castration produces testosterone-reversible increases in the density of 3H-naltrexone binding sites in the male rat brain. Unfortunately, we were unable to replicate these observations in a comprehensive series of studies. Specifically, we found that castration failed to produce changes in the Kd or Bmax of opiate binding sites in whole male rat brain, or in the hypothalamus, utilizing 3H-dihydromorphine (a mu receptor ligand), 3H-D-alanine, D-leucine enkephalin (delta) or 3H-naltrexone (ubiquitous). Furthermore, we found that the relative proportion of mu and delta binding sites in brain was unchanged by castration. The reasons for the discrepancy between the present results and those previously reported are unclear, but it appears that the provocative hypothesis that testosterone influences opioid receptors in brain must be carefully reevaluated. PMID:6310295

  14. Methylphenidate treatment leads to abnormalities on krebs cycle enzymes in the brain of young and adult rats.

    Science.gov (United States)

    Réus, Gislaine Z; Scaini, Giselli; Furlanetto, Camila B; Morais, Meline O S; Jeremias, Isabela C; Mello-Santos, Lis Mairá; Freitas, Karolina V; Quevedo, João; Streck, Emilio L

    2013-08-01

    Studies have shown a relationship between energy metabolism and methylphenidate (MPH); however, there are no studies evaluating the effects of MPH in Krebs cycle. So, we investigated if MPH treatment could alter the activity of citrate synthase (CS), malate dehydrogenase (MD), and isocitrate dehydrogenase (ID) in the brain of young and adult Wistar rats. Our results showed that MPH (2 and 10 mg/kg) reduced CS in the striatum and prefrontal cortex (PF), with MPH at all doses in the cerebellum and hippocampus after chronic treatment in young rats. In adult rats the CS was reduced in the cerebellum after acute treatment with MPH at all doses, and after chronic treatment in the PF and cerebellum with MPH (10 mg/kg), and in the hippocampus with MPH (2 and 10 mg/kg). The ID decreased in the hippocampus and striatum with MPH (2 and 10 mg/kg), and in the cortex (10 mg/kg) after acute treatment in young rats. In adult rats acute treatment with MPH (2 and 10 mg/kg) reduced ID in the cerebellum, and with MPH (10 mg/kg) in the cortex; chronic treatment with MPH (10 mg/kg) decreased ID in the PF; with MPH (2 and 10 mg/kg) in the cerebellum, and with MPH at all doses in the hippocampus. The MD did not alter. In conclusion, our results suggest that MPH can alter enzymes of Krebs cycle in brain areas involved with circuits related with attention deficit hyperactivity disorder; however, such effects depend on age of animal and treatment regime.

  15. Dynamic effects of point source electroporation on the rat brain tissue.

    Science.gov (United States)

    Sharabi, Shirley; Last, David; Guez, David; Daniels, Dianne; Hjouj, Mohammad Ibrahim; Salomon, Sharona; Maor, Elad; Mardor, Yael

    2014-10-01

    In spite of aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme due to tumor infiltration into the surrounding brain as well as poor blood-brain barrier penetration of most therapeutic agents. In this paper we present a novel approach for a minimally invasive treatment and a non-invasive response assessment methodology consisting of applying intracranial point-source electroporation and assessing treatment effect volumes using magnetic resonance imaging. Using a unique setup of a single intracranial electrode and an external surface electrode we treated rats' brains with various electroporation protocols and applied magnetic resonance imaging to study the dependence of the physiological effects on electroporation treatment parameters. The extent of blood-brain barrier disruption and later volumes of permanent brain tissue damage were found to correlate significantly with the treatment voltages (r(2)=0.99, pelectroporation when planning a treatment for brain tumors.

  16. Spontaneous Wheel Running Exercise Induces Brain Recovery via Neurotrophin-3 Expression Following Experimental Traumatic Brain Injury in Rats.

    Science.gov (United States)

    Koo, Hyun Mo; Lee, Sun Min; Kim, Min Hee

    2013-09-01

    [Purpose] The aim of the present study was to investigate the expression of neurotrophin-3 (NT-3) after applying spontaneous wheel running exercises (SWR) after experimental traumatic brain injury (TBI). [Subjects and Methods] Thirty male Sprague-Dawley rats were divided into 3 groups; 20 rats were subjected to controlled cortical impact for TBI, and then, animals were randomly collected from the SWR group and subjected to wheel running exercise for 3 weeks. Ten rats were not subjected to any injury or running exercise to compare with the effect of TBI and SWR. Immunohistochemistry, Western blotting, skilled ladder rung walking test, and 2,3,5-triphenyltetrazolium chloride staining analysis for the evaluation of NT-3 expression were used to assess brain damage and recovery. [Results] The TBI-induced decrease in NT-3 expression was recovered by wheel running exercise. Moreover, decreased ischemic volume and progressive neurobehavioral outcome were observed in the SWR group. [Conclusion] Spontaneous running exercise promotes brain recovery and motor function through an increase in expression of NT-3. PMID:24259924

  17. Cholestasis induced antinociception and decreased gene expression of MOR1 in rat brain.

    Science.gov (United States)

    Ahmadi, S; Karami, Z; Mohammadian, A; Khosrobakhsh, F; Rostamzadeh, J

    2015-01-22

    We examined antinociception and gene expression of mu-opioid receptor 1 (MOR1) in some brain areas of cholestatic rats, 21 days after common bile duct ligation (BDL). Cholestasis was induced in male Wistar rats during laparotomy and common BDL. Pain behavior was assessed on days 7, 14 or 21 of BDL using a hotplate test in control, sham and cholestatic groups. On day 21 of BDL, other groups of rats were sacrificed, whole brains were extracted, and the hypothalamus, prefrontal cortex (PFC), hippocampus and striatum in control, sham and cholestatic rats were dissected. We used a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method for evaluating MOR1 gene expression. The results revealed that cholestatic rats showed significant antinociception on days 14 and 21 of ligation with the most significant effect on day 21, which was prevented by naloxone (1 mg/kg). On the other hand, the expression of MOR1 gene compared to the sham group was decreased by 42% in the hypothalamus, 41% in the PFC, and 67% in the hippocampus after 21 days of BDL, while no significant change in its expression in the striatum was observed. It can be concluded that a change in endogenous opioid levels and its subsequent influence on the gene expression of MOR in some areas of the rat brain may underlie the altered nociception and other possible pathological changes such as pruritus after induction of cholestasis. PMID:25290008

  18. Effects of aging on abdominal wall healing in rats

    Directory of Open Access Journals (Sweden)

    Biondo-Simões Maria de Lourdes Pessole

    2005-01-01

    Full Text Available PURPOSE: The aim of this study was to assess abdominal wall healing in old and young adult rats. METHODS: On average, young animals were 110 days old and old animals were 762 days old. A 4.0 cm median laparotomy was performed under anesthesia, followed by laparorrhaphy on two synthesis planes, i.e. peritoneum-muscle-aponeurosis and skin, using continuous 5.0 nylon sutures. The animals were evaluated on the 3rd, 7th, 14th and 21st postoperative days. The resistance of the two planes was studied separately and a histopathologic analysis was performed on sections stained with hematoxylin-eosin and Sirius Red. Immunohistochemical analysis was also carried out using PCNA, LCA and CD34. RESULTS: The skin scars gained resistance in a similar manner at the initial time points, but those of young rats were more resistant on the 21st day (p=0.0029. Total and type III collagen content was similar in the two groups and type I collagen content was higher in young animals on the 14th day. Inflammatory cell infiltration was more marked in the skin wounds of young animals on the 3rd day (p=0.0190. Reepithelialization was similar and angiogenesis was more intense in the skin wounds of young animals on the 14th day (p=0.0062. The peritoneum-muscle-aponeurosis wounds gained similar resistance during the early phases, but were more resistant on the 14th day (p=0.0005 and on the 21st day (p=0.0023 in old rats Collagen concentration was higher in the wounds of old animals on the 3rd day (p=0.0112 and in the wounds of young animals on the 21st day (p=0.0348. The inflammatory reaction was more intense in the wounds of old animals on the 3rd day (p=0.0060 and angiogenesis was more intense on the 14th day (0.0432. CONCLUSION: Although there are some differences in the healing course between young and old animals, age, of itself, does not impair the healing of abdominal wall wounds in rats.

  19. Association of structural global brain network properties with intelligence in normal aging.

    Directory of Open Access Journals (Sweden)

    Florian U Fischer

    Full Text Available Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60-85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience.

  20. The impact of chronic stress on the rat brain lipidome

    OpenAIRE

    Oliveira, Tiago Gil; Chan, Robin B.; Bravo, Francisca Vaz; Miranda, André; Silva, Rita Ribeiro; Zhou, Bowen; Marques, Fernanda; Pinto, Vítor; Cerqueira, João José; Di Paolo, Gilbert; Sousa, Nuno

    2015-01-01

    Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer’s disease (AD) and depression. Lipids are a major constituent of the brain, and specifically signaling lipids have been shown to regulate brain fu...

  1. Novel microRNAs differentially expressed during aging in the mouse brain.

    Directory of Open Access Journals (Sweden)

    Sachi Inukai

    Full Text Available MicroRNAs (miRNAs are endogenous small RNA molecules that regulate gene expression post-transcriptionally. Work in Caenorhabditis elegans has shown that specific miRNAs function in lifespan regulation and in a variety of age-associated pathways, but the roles of miRNAs in the aging of vertebrates are not well understood. We examined the expression of small RNAs in whole brains of young and old mice by deep sequencing and report here on the expression of 558 known miRNAs and identification of 41 novel miRNAs. Of these miRNAs, 75 known and 18 novel miRNAs exhibit greater than 2.0-fold expression changes. The majority of expressed miRNAs in our study decline in relative abundance in the aged brain, in agreement with trends observed in other miRNA studies in aging tissues and organisms. Target prediction analysis suggests that many of our novel aging-associated miRNAs target genes in the insulin signaling pathway, a central node of aging-associated genetic networks. These novel miRNAs may thereby regulate aging-related functions in the brain. Since many mouse miRNAs are conserved in humans, the aging-affected brain miRNAs we report here may represent novel regulatory genes that also function during aging in the human brain.

  2. Brain Activation Patterns at Exhaustion in Rats That Differ in Inherent Exercise Capacity

    OpenAIRE

    Foley, Teresa E.; Leah R Brooks; Gilligan, Lori J.; Burghardt, Paul R.; Koch, Lauren G.; Britton, Steven L.; Monika Fleshner

    2012-01-01

    In order to further understand the genetic basis for variation in inherent (untrained) exercise capacity, we examined the brains of 32 male rats selectively bred for high or low running capacity (HCR and LCR, respectively). The aim was to characterize the activation patterns of brain regions potentially involved in differences in inherent running capacity between HCR and LCR. Using quantitative in situ hybridization techniques, we measured messenger ribonuclease (mRNA) levels of c-Fos, a mark...

  3. Diurnal variation of β-endorphin like immunoreactivity in rat brain, pituitary gland, and plasma

    International Nuclear Information System (INIS)

    β-endorphin like immunoreactivity was measured in the brain, pituitary gland and plasma of rats at 2 A.M, 8 A.M, 2 P.M and 8 P.M. Values were higher in the brain and pituitary gland at 8 P.M and in the plasma at 8 A.M and 2 P.M. The findings suggest a circadian rhythm in the production and release of β-endorphin immunoreactive material. (Author)

  4. Neuroprotection of erythropoietin in a model of neurodegeneration in the immature rat brain after hyperoxie exposure

    OpenAIRE

    Löber, Rebekka

    2011-01-01

    The exposition of hyperoxie contributes to apoptotic neurodegeneration in the immature rat brain by inhibiting growth factor signaling cascades and inducing apoptitic pathways by the caspase cascade. The exogen application of erythropoietin is able to reduce the apoptotic damage by inducing BDNF and his protective signaling cascades by ERK 1/2 and Akt and to decrease the activity of the caspase cascade. Erythropoietin is a promising candidate for neuroprotection in the immature brain.

  5. Effect of cyclosporin on distribution of methotrexate into the brain of rats.

    Science.gov (United States)

    Ogushi, Naofumi; Sasaki, Kazuaki; Shimoda, Minoru

    2015-09-01

    The effect of the antitumor drug, methotrexate (MTX), which is applied to brain tumors, is restricted by the blood-brain barrier (BBB), which is composed of P-glycoprotein (P-gp) and multidrug resistance associated protein (MRP). We, therefore, studied if a potent P-gp and MRP modulator, cyclosporin A (CysA), can modulate the MTX concentration in the rat brain. If it can, which route is more effective, intravenous or intrathecal? We intravenously or intrathecally administered MTX to rats with or without CysA. After 6 hr, brains and cerebrospinal fluid (CSF) were sampled, and their MTX concentrations were compared. Each MTX concentration was determined by high-performance liquid chromatography with UV detection. CysA had no significant affect on the MTX concentration in the brain or CSF when MTX was intravenously injected. In contrast, when MTX was intrathecally administered, CysA had a larger effect on the MTX concentration in the brain than in the CSF. This indicates CysA potentiated the brain MTX concentration when MTX was intrathecally administered. It is suggested that CysA did not potentiate the distribution of MTX from blood into the brain, but instead potentiated the distribution of MTX from CSF into the brain. Since chemicals in CSF generally diffuse into the brain easily, CysA probably inhibited the excretion of MTX from the brain. This could be caused by inhibition of P-gp or MRP at the BBB. Therefore, CysA can be a useful tool to achieve an appropriate MTX concentration in brain. PMID:25947324

  6. Age-dependent seizures of absence epilepsy and sleep spindles dynamics in WAG/Rij rats

    Science.gov (United States)

    Grubov, Vadim V.; Sitnikova, Evgenia Y.; Pavlov, Alexey N.; Khramova, Marina V.; Koronovskii, Alexey A.; Hramov, Alexander E.

    2015-03-01

    In the given paper, a relation between time-frequency characteristics of sleep spindles and the age-dependent epileptic activity in WAG/Rij rats is discussed. Analysis of sleep spindles based on the continuous wavelet transform is performed for rats of different ages. It is shown that the epileptic activity affects the time-frequency intrinsic dynamics of sleep spindles.

  7. Age-related increase in prostacyclin production in the rat aorta.

    Science.gov (United States)

    Panganamala, R V; Hanumaiah, B; Merola, A J

    1981-02-01

    Normal Sprague-Dawley rats convert a substantial percentage of exogenous arachidonic acid to prostacyclin. This conversion can be quantitated by an aqueous sampling technique utilizing thin layer chromatography and liquid scintillation counting. There is a clear age-related increase in this conversion that can be demonstrated in aortas from rats of 3 weeks to 20 weeks of age. PMID:7017783

  8. Supplementation with green tea polyphenols improves bone microstructure and quality in aged, orchidectomized rats

    Science.gov (United States)

    Recent studies show that green tea polyphenols (GTP) attenuate bone loss and microstructure deterioration in ovariectomized aged female rats, a model of postmenopausal osteoporosis. However, it is not known if such an osteo-protective role of GTP is demonstrable in androgen-deficient aged rats, a mo...

  9. Microglial cell dysregulation in brain aging and neurodegeneration

    OpenAIRE

    von Bernhardi, Rommy; Eugenín-von Bernhardi, Laura; Eugenín, Jaime

    2015-01-01

    Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergoes phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of c...

  10. Tracking of magnetite labeled nanoparticles in the rat brain using MRI.

    Directory of Open Access Journals (Sweden)

    Naira P Martínez Vera

    Full Text Available This study was performed to explore the feasibility of tracing nanoparticles for drug transport in the healthy rat brain with a clinical MRI scanner. Phantom studies were performed to assess the R1 ( =  1/T1 relaxivity of different magnetically labeled nanoparticle (MLNP formulations that were based on biodegradable human serum albumin and that were labeled with magnetite of different size. In vivo MRI measurements in 26 rats were done at 3T to study the effect and dynamics of MLNP uptake in the rat brain and body. In the brain, MLNPs induced T1 changes were quantitatively assessed by T1 relaxation time mapping in vivo and compared to post-mortem results from fluorescence imaging. Following intravenous injection of MLNPs, a visible MLNP uptake was seen in the liver and spleen while no visual effect was seen in the brain. However a histogram analysis of T1 changes in the brain demonstrated global and diffuse presence of MLNPs. The magnitude of these T1 changes scaled with post-mortem fluorescence intensity. This study demonstrates the feasibility of tracking even small amounts of magnetite labeled NPs with a sensitive histogram technique in the brain of a living rodent.

  11. Naoxintong dose effects on inflammatory factor expression in the rat brain following focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Xiangjian Zhang; Li Xü; Zuoran Chen; Shuchao Hu; Liying Zhang; Haiyan Li; Ruichun Liu

    2008-01-01

    BACKGROUND: Certain components of tetramethylpyrazine, a traditional Chinese medicine, exhibit protective effects against brain injury.OBJECTIVE: To investigate the effects of different Naoxintong doses on expression of nuclear factor-kappa B (κ B), interleukin-6, tumor necrosis factor-α, and complement 3 in rats following focal cerebral ischemia.DESIGN, TIME AND SETTING: The randomized experiment was performed at the Laboratory of Neurology, Second Hospital of Hebei Medical University from June 2004 to June 2006. MATERIAIS: A total of 150 adult, healthy, male, Sprague Dawley rats, weighing 280-320 g, were selected. Naoxintong powder (mainly comprising szechwan lovage rhizome, milkvetch root, danshen root, and radix angelicae sinensis) was obtained from Buchang Pharmacy Co., Ltd. in Xianyang City of Shanxi Province of China, lot number 040608.METHODS: The rats were randomly assigned into sham operation, saline, high-dose Naoxintong, moderate-dose Naoxintong, and low-dose Naoxintong groups, with 30 rats in each group. Rat models of middle cerebral artery occlusion were established using the suture method, with the exception of the sham operation group. Rats in the high-dose, moderate-dose and low-dose Naoxintong groups received 4, 2, and 1 glkg Naoxintong respectively, by gavage. Rats in the saline group were treated with 1 mL saline by gavage. All rats were administered by garage at 5 and 23 hours following surgery, and subsequently, once per day.MAIN OUTCOME MEASURES: At 6, 24, 48, 72 hours, and 7 days following model establishment, brain water content was measured. Histopathological changes in brain tissues were detected using hematoxylin-eosin staining. Expression of nuclear factor- κB, interleukin-6, tumor necrosis factor-α, and complement 3 was examined by immunohistochemistry.RESULTS: A total of 150 rats were included in the final analysis with no loss. Brain water content was significantly increased in the ischemic hemisphere of rats from the saline, as

  12. Compromised Blood-Brain Barrier Competence in Remote Brain Areas in Ischemic Stroke Rats at Chronic Stage

    Science.gov (United States)

    Garbuzova-Davis, Svitlana; Haller, Edward; Williams, Stephanie N.; Haim, Eithan D.; Tajiri, Naoki; Hernandez-Ontiveros, Diana G.; Frisina-Deyo, Aric; Boffeli, Sean M.; Sanberg, Paul R.; Borlongan, Cesario V.

    2014-01-01

    Stroke is a life threatening disease leading to long-term disability in stroke survivors. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from initial ischemic lesion, i.e. diaschisis. Previously, we showed that the damaged blood-brain barrier (BBB) was implicated in subacute diaschisis. The present study investigated BBB competence in chronic diaschisis using a transient middle cerebral artery occlusion (tMCAO) rat model. Our results demonstrated significant BBB damage mostly in the ipsilateral striatum and motor cortex in rats at 30 days after tMCAO. The BBB alterations were also determined in the contralateral hemisphere via ultrastructural and immunohistochemical analyses. Major BBB pathological changes in contralateral remote striatum and motor cortex areas included: (1) vacuolated endothelial cells containing large autophagosomes, (2) degenerated pericytes displaying mitochondria with cristae disruption, (3) degenerated astrocytes and perivascular edema, (4) Evans Blue extravasation, and (5) appearance of parenchymal astrogliosis. Importantly, discrete analyses of striatal and motor cortex areas revealed significantly higher autophagosome accumulation in capillaries of ventral striatum and astrogliosis in dorsal striatum in both cerebral hemispheres. These widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggest persistent and/or continued BBB damage in chronic ischemia. The pathological changes in remote brain areas likely indicate chronic ischemic diaschisis, which should be considered in the development of treatment strategies for stroke. PMID:24610730

  13. Altered angiotensin-converting enzyme and its effects on the brain in a rat model of Alzheimer disease

    Institute of Scientific and Technical Information of China (English)

    HOU De-ren; WANG Yan; ZHOU Lin; CHEN Kun; TIAN Yi; SONG Zhi; BAO Juan; YANG Qi-dong

    2008-01-01

    Background Alzheimer disease (AD) is a neurodegenerative disease related to aging.At present,its pathological mechanisms remain unclear.Family members of the renin-angiotensin system (RAS) pray a role in neuronal plasticity,as well as formation of learning and memory,in this study,we explore the effects of altered angiotensin-converting enzyme (ACE),and investigate the possible mechanisms of perindopril,an ACE inhibitor,on brain structure and function in a rat model of AD,as well as the role that ACE plays in AD.Methods Sixty Sprague-Dawley rats were selected and randomly divided into 3 groups:control,AD,and perindopril.Each group consisted of 20 rats,with 10 rats for determining pathology,and the remaining 10 rats for quantifying ACE activity.The rat AD model was established by stereotactically injecting amyloid beta protein (A-beta) 1-42 into the right hippocampus.Learning and memory functions were tested using the Y-type electric maze.The number and morphology of abnormal neurons were determined by haematoxylin and eosin staining.Amyloid deposition was measured by Congo red staining.Finally,ACE activity was estimated by spectrophotometry.Results Compared with the control group,the number of times needed to escape electrical stimuli increased (23.70±3.13,P <0.001),the number of normal neurons in the CA1 region was reduced (density of 96.5±32.6/mm,Pgroup.In the perindopril group,the number of times needed to escape electrical stimuli decreased (18.50±3.66,P <0.001),the number of abnormal neurons increased (density of CA1 neurons was 180.8±28.5/mm,P <0.001),amyloid Conclusions ACE activity increased in the brains of AD rats.Perindopril improved learning and memory in AD rats,which correlated with decreased ACE activity and delayed AD pathogenesis.

  14. Haptoglobin increases with age in rat hippocampus and modulates Apolipoprotein E mediated cholesterol trafficking in neuroblastoma cell lines

    Directory of Open Access Journals (Sweden)

    Maria Stefania eSpagnuolo

    2014-08-01

    Full Text Available Alteration in cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative disorders. Apolipoprotein E (ApoE is the major component of brain lipoproteins supporting cholesterol transport. We previously reported that the acute-phase protein Haptoglobin (Hpt binds ApoE, and influences its function in blood cholesterol homeostasis. Major aim of this study was to investigate whether Hpt influences the mechanisms by which cholesterol is shuttled from astrocytes to neurons. In detail it was studied Hpt effect on ApoE-dependent cholesterol efflux from astrocytes and ApoE-mediated cholesterol incorporation in neurons. We report here that Hpt impairs ApoE-mediated cholesterol uptake in human neuroblastoma cell line SH-SY5Y, and limits the toxicity of a massive concentration of cholesterol for these cells, while it does not affect cholesterol efflux from the human glioblastoma-astrocytoma cell line U-87 MG. As aging is the most important nongenetic risk factor for various neurodegenerative disorders, and our results suggest that Hpt modulates ApoE functions, we evaluated the Hpt and ApoE expression profiles in cerebral cortex and hippocampus of adolescent (2 months, adult (5 and 8 months, and middle-aged (16 months rats. Hpt mRNA level was higher in hippocampus of 8 and 16 month-old than in 2-month old rats (p<0.05, and Hpt concentration increased with the age from adolescence to middle-age (p<0.001. ApoE concentration, in hippocampus, was higher (p<0.001 in 5 month-old rats compared to 2 month but did not further change with aging. No age-related changes of Hpt (protein and mRNA were found in the cortex. Our results suggest that aging is associated with changes, particularly in the hippocampus, in the Hpt/ApoE ratio. Age-related changes in the concentration of Hpt were also found in human cerebrospinal fluids.The age-related changes might affect neuronal function and survival in brain, and have important implications in

  15. A longitudi