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Sample records for rat brain exposed

  1. Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats.

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    Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

    2006-02-16

    Free radicals mediated oxidative stress has been implicated in the pathogenesis of smoking-related diseases and antioxidant nutrients are reported to prevent the oxidative damage induced by smoking. Therefore, the present study was conducted to evaluate the antioxidant role of bacoside A (triterpenoid saponin isolated from Bacopa monniera) against chronic cigarette smoking induced oxidative damage in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with bacoside A (10 mg/kg b.w./day, p.o.). Antioxidant status of the brain was assessed from the levels of reduced glutathione, vitamin C, vitamin E, and vitamin A and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The levels of copper, iron, zinc and selenium in brain and serum ceruloplasmin activity were also measured. Oxidative stress was evident from the diminished levels of both enzymatic and non-enzymatic antioxidants. Alterations in the levels of trace elements with accumulation of copper and iron, and depletion of zinc and selenium were also observed. Bacoside A administration improved the antioxidant status and maintained the levels of trace elements. These results suggest that chronic cigarette smoke exposure enhances oxidative stress, thereby disturbing the tissue defense system and bacoside A protects the brain from the oxidative damage through its antioxidant potential.

  2. N-Butylphthalide Alleviates Blood-Brain Barrier Impairment in Rats Exposed to Carbon Monoxide

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    Mingjun Bi

    2016-10-01

    Full Text Available Carbon monoxide (CO poisoning is one of the most important health concerns and may result in neuropathologic changes and neurologic sequelae. However, few studies have addressed the correlation between CO poisoning and blood-brain barrier (BBB impairment. In this study, we investigated the effects of N-butylphthalide (NBP on the expressions of zonula occludens-1 (ZO-1, claudin-5 and aquaporin-4 (AQP-4 proteins in a CO poisoning rat model. The results indicated that the brain water content was obviously increased, and the tight junctions (TJs between endothelial cells were disrupted, resulting in significant cerebral edema and BBB dysfunction in a rat model of CO poisoning. Meanwhile, the ultrastructure of endothelial cells and pericytes was seriously damaged, and the expressions of ZO-1 and claudin-5 were decreased at an early stage (<7 days. NBP treatment could efficiently maintain the ultrastructural and functional integrity of BBB, alleviate cerebral edema. Besides, NBP could also markedly increase the levels of both ZO-1 and claudin-5 proteins compared with those in rats exposed to CO (P<0.05, whereas NBP had no apparent regulatory effect on AQP-4 expression. Taken together, this study highlights the importance of ZO-1 and claudin-5 proteins in maintaining BBB ultrastructure and function after CO poisoning. NBP, as a novel treatment approach, may effectively inhibit the down-regulation of ZO-1 and claudin-5 proteins (but not AQP-4, thereby preserving the barrier function and reducing cerebral edema after CO poisoning.

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

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    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.

  4. Alterations of metallothionein isomers in Hg{sup 0}-exposed rat brain

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    Yasutake, A. [Biochemistry Section, National Institute for Minamata Disease, Minamata, Kumamoto 867-0008 (Japan); Nagano, M. [Morikawa Kenkodo Co., Ltd., 2170 Taguchi, Kosa, Kamimashiki, Kumamoto 861-4616 (Japan); Hirayama, K. [Kumamoto University College of Medical Science, Kuhonji, Kumamoto 862-0976 (Japan)

    2003-01-01

    Previously we found that exposure to mercury vapor effectively induced brain metallothionein (MT) in rats. Here, using FPLC-gel chromatography, we examined time-dependent alterations in the MT isomers, MT-I/II and MT-III, following 3 weeks of exposure. Rats were exposed to mercury vapor at 8.3 mg/m{sup 3} for 15 h in total over 5 consecutive days. Total MT levels in rat cerebrum and cerebellum increased by 65% and 155%, respectively, 24 h after the final exposure. The increased levels in both tissues remained unchanged for at least 2 weeks after termination of exposure. Interestingly, most MT in control rat cerebrum and cerebellum was accounted for by MT-III, with MT-I/II being less than 10%. Through mercury vapor exposure, MT-I/II was quickly induced to a significant extent in both tissues, reaching a level comparable to that of MT-III. The induction rate of MT-I/II in the cerebellum was somewhat higher than in the cerebrum. Chromatograms showed that the MT-I/II thus induced began to decline at an early stage in both tissues. In the cerebrum, the amount of MT-I/II on day 22 was about 30% of the maximum level on day 1. On the other hand, the induction of MT-III was not that dramatic, but it did become evident, at least in the latter stage, when MT-I/II had begun to decrease. Thus, though the induction rate of MT-III was not as high as MT-I/II, it was sustained throughout the experimental period. (orig.)

  5. L-DEPRENYL REDUCES BRAIN-DAMAGE IN RATS EXPOSED TO TRANSIENT HYPOXIA-ISCHEMIA

    NARCIS (Netherlands)

    KNOLLEMA, S; AUKEMA, W; HOM, H; KORF, J; TERHORST, GJ

    1995-01-01

    Background and Purpose L-Deprenyl (Selegiline) protects animal brains against toxic substances such as 1-methyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine. Experiments were conducted to test whether L-deprenyl prevents or reduces cerebral damage in a transient hypoxia/ischemia rat model. Metho

  6. 1H MRS-detectable metabolic brain changes and reduced impulsive behavior in adult rats exposed to methylphenidate during adolescence.

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    Adriani, W; Canese, R; Podo, F; Laviola, G

    2007-01-01

    Administration of methylphenidate (MPH, Ritalin) to children affected by attention deficit hyperactivity disorder (ADHD) is an elective therapy, which however raises concerns for public health, due to possible persistent neuro-behavioral alterations. We investigated potential long-term consequences at adulthood of MPH exposure during adolescence, by means of behavioral and brain MRS assessment in drug-free state. Wistar adolescent rats (30- to 44-day-old) were treated with MPH (0 or 2 mg/kg once/day for 14 days) and then left undisturbed until adulthood. Levels of impulsive behavior were assessed in the intolerance-to-delay task: Food-restricted rats were tested in operant chambers with two nose-poking holes, delivering one food pellet immediately, or five pellets after a delay whose length was increased over days. MPH-exposed animals showed a less marked shifting profile from the large/late to the small/soon reward, suggesting reduced basal levels of impulsivity, compared to controls. In vivo MRI-guided 1H MRS examinations at 4.7 T in anaesthetised animals revealed long-term biochemical changes in the dorsal striatum (STR), nucleus accumbens (NAcc), and prefrontal cortex (PFC) of MPH-exposed rats. Notably, total creatine and taurine, metabolites respectively involved in bioenergetics and synaptic efficiency, were up-regulated in the STR and conversely down-regulated in the NAcc of MPH-exposed rats. A strong correlation was evident between non-phosphorylated creatine in the STR and behavioral impulsivity. Moreover, unaltered total creatine and increased phospho-creatine/creatine ratio were detected in the PFC, suggesting improved cortical energetic performance. Because of this enduring rearrangement in the forebrain function, MPH-exposed animals may be more efficient when faced with delay of reinforcement. In summary, MPH exposure during adolescence produced enduring MRS-detectable biochemical modifications in brain reward-related circuits, which may account for

  7. Inflammation-like glial response in lead-exposed immature rat brain.

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    Struzynska, Lidia; Dabrowska-Bouta, Beata; Koza, Katarzyna; Sulkowski, Grzegorz

    2007-01-01

    Numerous studies on lead (Pb) neurotoxicity have indicated this metal to be a dangerous toxin, particularly during developmental stages of higher organisms. Astrocytes are responsible for sequestration of this metal in brain tissue. Activation of astroglia may often lead to loss of the buffering function and contribute to pathological processes. This phenomenon is accompanied by death of neuronal cells and may be connected with inflammatory events arising from the production of a wide range of cytokines and chemokines. The effects of prolonged exposure to Pb upon glial activation are examined in immature rats to investigate this potential proinflammatory effect. When analyzed at the protein level, glial activation is observed after Pb exposure, as reflected by the increased level of glial fibrillary acidic protein and S-100beta proteins in all parts of the brain examined. These changes are associated with elevation of proinflammatory cytokines. Production of interleukin (IL)-1beta and tumor necrosis factor-alpha is observed in hippocampus, and production of IL-6 is seen in forebrain. The expression of fractalkine is observed in both hippocampus and forebrain but inconsiderably in the cerebellum. In parallel with cytokine expression, signs of synaptic damage in hippocampus are seen after Pb exposure, as indicated by decreased levels of the axonal markers synapsin I and synaptophysin. Obtained results indicate chronic glial activation with coexisting inflammatory and neurodegenerative features as a new mechanism of Pb neurotoxicity in immature rat brain.

  8. Investigation of toxic factors affecting cells of rat brains exposed to 3-methylcatechol

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    George Emílio Sampaio Barreto

    2007-09-01

    Full Text Available The aim of this work was to study the effects of 3MC on the peroxidation of biomolecules in nuclear fractions and nonsynaptic mitochondrial respiration in organelles obtained from rat brains. The cytotoxicity towards rat primary astrocytes in vitro was also tested. 3MC at 1mM oxidized consuming oxygen at a rate of 1.98 ± 0.19 µM.min-1 and formed reactive quinones. At the same concentration, 3MC induced peroxidation of biomolecules in nuclear fractions obtained from rat brain homogenates and inhibited state 2 FADH2-linked respiration in nonsynaptic mitochondria. Furthermore, 3MC oxidized in the culture medium, leading to the formation of quinones. This toluene metabolite was cytotoxic to rat primary astrocytes. The concentration that killed 50% of cells after 72 h was 107 mM. The results of the study indicated a direct relationship between cytotoxicity and 3MC oxidation.O 3-metilcatecol (3MC é um metabólito do tolueno. Para esclarecer se o 3MC seria tóxico para o sistema nervoso central, examinou-se seus efeitos sobre a peroxidação de biomoléculas em frações nucleares e a respiração mitocondrial em organelas obtidas de cérebros de ratos. Também se testou a citotoxicidade para astrócitos primários de ratos. O 3MC a 1mM oxida-se consumindo oxigênio a uma taxa de 1,98 ± 0,19 mM.min-1, formando quinonas reativas. Nessa mesma concentração o 3MC peroxidou biomoléculas nas frações nucleares. Esse composto também inibiu o estado 2 da respiração mitocondrial associada ao FADH2. Além disso, o 3MC também se oxida em meio de cultura levando à formação de quinonas. Esse metabólito do tolueno foi citotóxico para astrócitos de ratos. A concentração que matou 50% das células após 72 horas foi 107 mM. Os resultados desse estudo indicam uma relação direta entre a citotoxicidade e a oxidação do 3MC.

  9. Effect of bacoside A on membrane-bound ATPases in the brain of rats exposed to cigarette smoke.

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    Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

    2005-01-01

    Membrane-bound enzymes play a vital role in neuronal function through maintenance of membrane potential and impulse propagation. We have evaluated the harmful effects of chronic cigarette smoking on membrane-bound ATPases and the protective effect of Bacoside A in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with Bacoside A (the active principle isolated from Bacopa monniera) at a dosage of 10 mg/kg b.w/day, p.o. The levels of lipid peroxides as marker for evaluating the extent of membrane damage, the activities of Na+/K+-ATPase, Ca2+-ATPase and Mg2+-ATPase, and associated cations sodium (Na+), potassium (K+), calcium (Ca2+), and magnesium (Mg2+) were investigated in the brain. Neuronal membrane damage was evident from the elevated levels of lipid peroxides and decreased activities of membrane-bound enzymes. Disturbances in the electrolyte balance with accumulation of Na+ and Ca2+ and depletion of K+ and Mg2+ were also observed. Administration of Bacoside A inhibited lipid peroxidation, improved the activities of ATPases, and maintained the ionic equilibrium. The results of our study indicate that Bacoside A protects the brain from cigarette smoking induced membrane damage.

  10. Evaluation of passive avoidance learning and spatial memory in rats exposed to low levels of lead during specific periods of early brain development.

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    Rao Barkur, Rajashekar; Bairy, Laxminarayana K

    2015-01-01

    Widespread use of heavy metal lead (Pb) for various commercial purposes has resulted in the environmental contamination caused by this metal. The studies have shown a definite relationship between low level lead exposure during early brain development and deficit in children's cognitive functions. This study investigated the passive avoidance learning and spatial learning in male rat pups exposed to lead through their mothers during specific periods of early brain development. Experimental male rats were divided into 5 groups: i) the normal control group (NC) (N = 12) consisted of rat offspring born to mothers who were given normal drinking water throughout gestation and lactation, ii) the pre-gestation lead exposed group (PG) (N = 12) consisted of rat offspring, mothers of these rats had been exposed to 0.2% lead acetate in the drinking water for 1 month before conception, iii) the gestation lead exposed group (G) (N = 12) contained rat offspring born to mothers who had been exposed to 0.2% lead acetate in the drinking water throughout gestation, iv) the lactation lead exposed group (L) (N = 12) had rat offspring, mothers of these rats exposed to 0.2% lead acetate in the drinking water throughout lactation and v) the gestation and lactation lead exposed group (GL) (N = 12) contained rat offspring, mothers of these rats were exposed to 0.2% lead acetate throughout gestation and lactation. The study found deficit in passive avoidance learning in the G, L and GL groups of rats. Impairment in spatial learning was found in the PG, G, L and GL groups of rats. Interestingly, the study found that gestation period only and lactation period only lead exposure was sufficient to cause deficit in learning and memory in rats. The extent of memory impairment in the L group of rats was comparable with the GL group of rats. So it can be said that postnatal period of brain development is more sensitive to neurotoxicity compared to prenatal exposure. This work is available in Open

  11. Influence of perinatal trans fat on behavioral responses and brain oxidative status of adolescent rats acutely exposed to stress.

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    Pase, C S; Roversi, Kr; Trevizol, F; Roversi, K; Kuhn, F T; Schuster, A J; Vey, L T; Dias, V T; Barcelos, R C S; Piccolo, J; Emanuelli, T; Bürger, M E

    2013-09-01

    Because consumption of processed foods has increased in the last decades and so far its potential influence on emotionality and susceptibility to stress is unknown, we studied the influence of different fatty acids (FA) on behavioral and biochemical parameters after acute restrain stress (AS) exposure. Two sequential generations of female rats were supplemented with soybean oil (control group; C-SO), fish oil (FO) and hydrogenated vegetable fat (HVF) from pregnancy and during lactation. At 41days of age, half the animals of each supplemented group were exposed to AS and observed in open field and elevated plus maze task, followed by euthanasia for biochemical assessments. The HVF-supplemented group showed higher anxiety-like symptoms per se, while the C-SO and FO groups did not show these behaviors. Among groups exposed to AS, HVF showed locomotor restlessness in the open field, while both C-SO and HVF groups showed anxiety-like symptoms in the elevated plus maze, but this was not observed in the FO group. Biochemical evaluations showed higher lipoperoxidation levels and lower cell viability in cortex in the HVF group. In addition, HVF-treated rats showed reduced catalase activity in striatum and hippocampus, as well as increased generation of reactive species in striatum, while FO was associated with increased cell viability in the hippocampus. Among groups exposed to AS, HVF increased reactive species generation in the brain, decreased cell viability in the cortex and striatum, and decreased catalase activity in the striatum and hippocampus. Taken together, our findings show that the type of FA provided during development and growth over two generations is able to modify the brain oxidative status, which was particularly adversely affected by trans fat. In addition, the harmful influence of chronic consumption of trans fats as observed in this study can enhance emotionality and anxiety parameters resulting from stressful situations of everyday life, which can

  12. The protective influence of selenium on oxidant disturbances in brain of rats exposed to lithium.

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    Kiełczykowska, M; Kocot, J; Lewandowska, A; Żelazowska, R; Musik, I

    2015-01-01

    For more than sixty years lithium carbonate has been used in medicine. However, during its administration different side effects including oxidative stress can occur. Selenium belongs to essential elements possessing antioxidant properties. This study aimed at evaluating if selenium could be used as a protective adjuvant in lithium therapy. The experiment was performed on four groups of Wistar rats: I (control), II (Li), III (Se), IV (Li + Se) treated with saline, lithium carbonate (2.7 mg Li/kg b.w.), sodium selenite (0.5 mg Se/kg b.w.) and lithium carbonate (2.7 mg Li/kg b.w.) + sodium selenite (0.5 mg Se/kg b.w.), respectively. All substances were administered as water solutions by stomach tube for 3 or 6 weeks. Catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as malonyldialdehyde (MDA) were determined in brain homogenates. Lithium slightly enhanced MDA and depressed CAT and SOD after 6 weeks as well as GPx after 3 weeks. Selenium co-administration showed tendency to restore the disturbed parameters. Selenium alone and given with lithium significantly increased GPx vs. Li-treated group after 3 weeks. Having regarded the outcomes of this study, the research on application of selenium during lithium treatment seems to be worth continuation.

  13. Furin mediates brain-derived neurotrophic factor upregulation in cultured rat astrocytes exposed to oxygen-glucose deprivation.

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    Chen, Yan; Zhang, Junjian; Deng, Min

    2015-01-01

    This study investigated the changes in brain-derived neurotrophic factor (BDNF) expression and the role of furin in BDNF maturation in reactive astrocytes from rats exposed to oxygen-glucose deprivation (OGD). Furin, a proprotein convertase, is upregulated and cleaves certain substrates during hypoxia in cancer cells. In addition, during hypoxia in the central nervous system, astrocytes become reactive and release BDNF to protect neurons. Maturation of BDNF in astrocytes requires furin-mediated endoproteolytic processing of the precursor protein pro-BDNF to BDNF. To expand our knowledge about the role of furin in BDNF maturation in astrocytes, these cells were exposed to OGD, and expression of furin and BDNF was detected by Western blot analysis. Changes in BDNF expression were observed when furin activity was inhibited by furin prosegment. We found that protein expression of BDNF and furin was upregulated, and this upregulation correlated with OGD stimulation. Furin inhibition reduced BDNF maturation and secretion. These results indicate that furin mediates the upregulation of BDNF in reactive astrocytes exposed to OGD and that furin may impact the biological effect of reactive astrocytes.

  14. Assessment of genotoxic and cytotoxic hazards in brain and bone marrow cells of newborn rats exposed to extremely low-frequency magnetic field.

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    Rageh, Monira M; El-Gebaly, Reem H; El-Bialy, Nihal S

    2012-01-01

    The present study aimed to evaluate the association between whole body exposure to extremely low frequency magnetic field (ELF-MF) and genotoxic , cytotoxic hazards in brain and bone marrow cells of newborn rats. Newborn rats (10 days after delivery) were exposed continuously to 50 Hz, 0.5 mT for 30 days. The control group was treated as the exposed one with the sole difference that the rats were not exposed to magnetic field. Comet assay was used to quantify the level of DNA damage in isolated brain cells. Also bone marrow cells were flushed out to assess micronucleus induction and mitotic index. Spectrophotometric methods were used to measure the level of malondialdehyde (MDA) and the activity of glutathione (GSH) and superoxide dismutase (SOD). The results showed a significant increase in the mean tail moment indicating DNA damage in exposed group (P < 0.01, 0.001, 0.0001). Moreover ELF-MF exposure induced a significant (P < 0.01, 0.001) four folds increase in the induction of micronucleus and about three folds increase in mitotic index (P < 0.0001). Additionally newborn rats exposed to ELF-MF showed significant higher levels of MDA and SOD (P < 0.05). Meanwhile ELF-MF failed to alter the activity of GSH. In conclusion, the present study suggests an association between DNA damage and ELF-MF exposure in newborn rats.

  15. Assessment of Genotoxic and Cytotoxic Hazards in Brain and Bone Marrow Cells of Newborn Rats Exposed to Extremely Low-Frequency Magnetic Field

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    Monira M. Rageh

    2012-01-01

    Full Text Available The present study aimed to evaluate the association between whole body exposure to extremely low frequency magnetic field (ELF-MF and genotoxic , cytotoxic hazards in brain and bone marrow cells of newborn rats. Newborn rats (10 days after delivery were exposed continuously to 50 Hz, 0.5 mT for 30 days. The control group was treated as the exposed one with the sole difference that the rats were not exposed to magnetic field. Comet assay was used to quantify the level of DNA damage in isolated brain cells. Also bone marrow cells were flushed out to assess micronucleus induction and mitotic index. Spectrophotometric methods were used to measure the level of malondialdehyde (MDA and the activity of glutathione (GSH and superoxide dismutase (SOD. The results showed a significant increase in the mean tail moment indicating DNA damage in exposed group (P<0.01,0.001,0.0001. Moreover ELF-MF exposure induced a significant (P<0.01,0.001 four folds increase in the induction of micronucleus and about three folds increase in mitotic index (P<0.0001. Additionally newborn rats exposed to ELF-MF showed significant higher levels of MDA and SOD (P<0.05. Meanwhile ELF-MF failed to alter the activity of GSH. In conclusion, the present study suggests an association between DNA damage and ELF-MF exposure in newborn rats.

  16. [Protective effect of hypothermia on brain neurons of rats exposed to ionizing radiation].

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    Gordon, R Ia; Ignat'ev, D A; Mel'nikova, E B; Rogachevskiĭ, V V; Kraev, I V; Hutsian, S S

    2007-01-01

    The conditions of the protein-synthesizing system in neurons of the hippocampus (areas CA1 and C A3) and of the cortex (sensomotor region) in rats subjected to y-irradiation at a dose of 8 Gy under hypothermia (16 - 18 degrees C) and hypoxia-hypercapnia were investigated by fluorescent and electron microscopy. Under hypothermia, the protein-synthesizing system was shown to be damaged to a lesser degree and to be restored faster in comparison with similar neurons in rats irradiated at room temperature. In rats irradiated under hypothermia, the rRNA biogenesis and the protein-synthesizing activity of polyribosomes were restored in two days. The protective influence of hypothermia did not spread to changes in membrane structures (endoplasmic reticulum and Golgy apparatus); i.e., a partial loss of integrity and possible transformation of their structure caused by the irradiation and the restoration of these structures occurred at a lower rate.

  17. Effect of voluntary alcohol consumption on Maoa expression in the mesocorticolimbic brain of adult male rats previously exposed to prolonged maternal separation

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    Bendre, M; Comasco, E; Nylander, I; Nilsson, K W

    2015-01-01

    Discordant associations between monoamine oxidase A (MAOA) genotype and high alcohol drinking have been reported in human and non-human primates. Environmental influences likely moderate genetic susceptibility. The biological basis for this interplay remains elusive, and inconsistencies call for translational studies in which conditions can be controlled and brain tissue is accessible. The present study investigated whether early life stress and subsequent adult episodic alcohol consumption affect Maoa expression in stress- and reward-related brain regions in the rat. Outbred Wistar rats were exposed to rearing conditions associated with stress (prolonged maternal separation) or no stress during early life, and given free choice between alcohol and/or water in adulthood. Transcript levels of Maoa were assessed in the ventral tegmental area, nucleus accumbens (NAc), medial prefrontal cortex, cingulate cortex, amygdala and dorsal striatum (DS). Blood was collected to assess corticosterone levels. After alcohol consumption, lower blood corticosterone and Maoa expression in the NAc and DS were found in rats exposed to early life stress compared with control rats. An interaction between early life stress and voluntary alcohol intake was found in the NAc. Alcohol intake before death correlated negatively with Maoa expression in DS in high alcohol-drinking rats exposed to early life stress. Maoa expression is sensitive to adulthood voluntary alcohol consumption in the presence of early life stress in outbred rats. These findings add knowledge of the molecular basis of the previously reported associations between early life stress, MAOA and susceptibility to alcohol misuse. PMID:26645625

  18. Brain glutathione content and glutamate uptake are reduced in rats exposed to pre- and postnatal protein malnutrition.

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    Feoli, Ana Maria; Siqueira, Ionara; Almeida, Lucia Maria V; Tramontina, Ana Carolina; Battu, Cíntia; Wofchuk, Susana T; Gottfried, Carmem; Perry, Marcos Luiz; Gonçalves, Carlos-Alberto

    2006-09-01

    The brain is particularly susceptible to oxidative insults and its antioxidant defense is dependent on its glutathione content. Protein malnutrition (PMN) is an important and very common insult during development and compromises antioxidant defenses in the body, particularly glutathione levels. We investigated whether brain glutathione content and related metabolic pathways, predominantly regulated by astrocytes (particularly glutamate uptake and glutamine synthesis), are altered by pre- and postnatal PMN in rats. Thus, we measured the glutathione content, glutamine synthetase (GS) activity, and glutamate uptake activity in the cerebral cortex (Cx) and hippocampus of rats subjected to pre- and postnatal PMN and in nourished controls. Although malnourished rats exhibited an ontogenetic profile of glutathione levels in both brain regions similar to that of controls, they had lower levels on postnatal d 2 (P2); in Cx this decrease persisted until postnatal d 15. In addition, we found other changes, such as reduced total antioxidant reactivity and glutathione peroxidase activity on P2, and these were not accompanied by alterations in free radical levels or lipoperoxidation in either brain region. Moreover, malnourished rats had elevated GS and reduced glutamate uptake. Taken together, these alterations indicate specific changes in astrocyte metabolism, possibly responsible for the higher vulnerability to excitotoxic/oxidative damage in malnourished rats. The lower antioxidant defense appears to be the main alteration that causes oxidative imbalance, rather than an increase in reactive oxygen species. Moreover, a recovery of altered metabolic variables may occur during adulthood, despite persistent PMN.

  19. Disordered redox metabolism of brain cells in rats exposed to low doses of ionizing radiation or UHF electromagnetic radiation.

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    Burlaka, A P; Druzhyna, M O; Vovk, A V; Lukin, S М

    2016-12-01

    To investigate the changes of redox-state of mammalian brain cells as the critical factor of initiation and formation of radiation damage of biological structures in setting of continuous exposure to low doses of ionizing radiation or fractionated ultra high frequency electromagnetic radiation (UHF EMR) at non-thermal levels. The influence of low-intensity ionizing radiation was studied on outbred female rats kept for 1.5 years in the Chernobyl accident zone. The effects of total EMR in the UHF band of non-thermal spectrum were investigated on Wistar rats. The rate of formation of superoxide radicals and the rate of NO synthesis in mitochondria were determined by the EPR. After exposure to ionizing or UHF radiation, the levels of ubisemiquinone in brain tissue of rats decreased by 3 and 1.8 times, respectively. The content of NO-FeS-protein complexes in both groups increased significantly (р < 0.05). In the conditions of ionizing or EMR the rates of superoxide radical generation in electron-transport chain of brain cell mitochondria increased by 1.5- and 2-fold, respectively (р < 0.05). In brain tissue of rats kept in the Chernobyl zone, significant increase of NO content was registered; similar effect was observed in rats treated with UHFR (р < 0.05). The detected changes in the electron transport chain of mitochondria of brain cells upon low-intensity irradiation or UHF EMR cause the metabolic reprogramming of cell mitochondria that increases the rate of superoxide radical generation and nitric oxide, which may initiate the development of neurodegenerative diseases and cancer. This article is part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

  20. Recovery of motor coordination after exercise is correlated to enhancement of brain-derived neurotrophic factor in lactational vanadium-exposed rats.

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    Wang, Dean-Chuan; Lin, Yu-Yi; Lin, Hwai-Ting

    2015-07-23

    Lactational exposure to vanadium can reduce the locomotor activity in adult animals. In this study, we investigated whether lactational vanadium exposure impairs the motor coordination and whether exercise ameliorates this dysfunction. Sprague-Dawley dams were treated with or without vanadium during lactation. The weaned male offspring were trained to treadmill running for 5 weeks and then examined their motor coordination on a rotarod. The neuroprotective effect of exercise was evaluated by the brain-derived neurotrophic factor (BDNF) in plasma and cerebellum. The results demonstrated that vanadium-exposed rats exhibited impaired motor coordination and reduced plasma and cerebellar BDNF levels. Treadmill running during childhood-adolescence prevented the impaired motor coordination in the lactational vanadium-exposed rats. The beneficial effect of treadmill running on motor coordination in the vanadium-exposed rats was correlated to the normalization of plasma and cerebellar BDNF levels, as well as the increased TrkB phosphorylation in the cerebellum. The result suggests that exercise may prevent the impairment of motor coordination in the lactational vanadium-exposed rats.

  1. Protective Effect of Ocimum basilicum on Brain Cells Exposed to Oxidative Damage by Electromagnetic Field in Rat: Ultrastructural Study by Transmission Electron Microscopy

    Directory of Open Access Journals (Sweden)

    Khaki Arash

    2016-01-01

    Full Text Available Objective: Basil herb (Ocimum basilicum has long been used in human nutrition. Nowadays antioxidant role of this herb is known more. The aim of this study was to study the anti-oxidative property of sweet basil to protect central nervous system against oxidative damages of electromagnetic field (EMF and its affective sequences. Materials and Methods: Forty Albino male Wistar rats were randomly allocated to four groups, 10 rats per each. Group 1 received normal diet (control group, group 2 was exposed to 50 Hz EMF for 8 weeks (EMF group. Group 3 was exposed to 50 Hz EMF and fed with basil extract (0.5 g/kg body weight for 8 weeks (treatment group and group 4 was fed with basil extract (0.5 g/kg body weight for 8 weeks and named as herbal group. At the end of eighth week 5 mL blood was taken from all rats for biochemical analysis and for ultra structural study of brain neuron samples was taken. Results: The results showed level of superoxide dismutase (SOD, glutathione (GSH peroxidase and catalase activity (CAT were significantly increased in herbal and treatment groups as compared to EMF group (P < 0.05. Level of malondialdehyde (MDA was significantly decreased in treatment group as compare to EMF group (P < 0.05. Ultra structural evaluation of EMF group showed brain nucleus has a lot of heterochromatic changes and mitochondria have been ovulated and have swelling figure this changes were less in treatment group. Conclusion: Antioxidant capacity of basil extract can cause to decrease oxidative effects of EMF on brain tissue and in rats.

  2. Dental Fluorosis and Catalase Immunoreactivity of the Brain Tissues in Rats Exposed to High Fluoride Pre- and Postnatally.

    Science.gov (United States)

    Güner, Şirin; Uyar-Bozkurt, Süheyla; Haznedaroğlu, Eda; Menteş, Ali

    2016-11-01

    This study evaluated dental fluorosis of the incisors and immunoreactivity in the brain tissues of rats given chronic fluoride doses pre- and postnatally. Female rats were given drinking water with 0, 30 or 100 ppm fluoride ad libitum throughout gestation and the nursing period. In addition, 63 male offspring were treated with the same water regimens as the mothers after weaning and were followed for 1, 3 or 5 months. The upper and lower incisors were collected, and all teeth were examined under a stereomicroscope and scored by two blinded examiners using a modified rodent enamel fluorosis index. Cortical, hippocampal and cerebellar brain samples were evaluated morphologically and immunohistochemically. All fluoride-treated pups were born with low body weight (p = 0.001). All animals from the fluoride groups had enamel fluorosis with defects of various degrees. The increase in the dental fluorosis scores in the fluoride treatment groups was significant (p fluoride groups was significantly higher than that in the controls after 1, 3 and 5 months (p fluoride.

  3. Real-time optical diagnosis of the rat brain exposed to a laser-induced shock wave: observation of spreading depolarization, vasoconstriction and hypoxemia-oligemia.

    Directory of Open Access Journals (Sweden)

    Shunichi Sato

    Full Text Available Despite many efforts, the pathophysiology and mechanism of blast-induced traumatic brain injury (bTBI have not yet been elucidated, partially due to the difficulty of real-time diagnosis and extremely complex factors determining the outcome. In this study, we topically applied a laser-induced shock wave (LISW to the rat brain through the skull, for which real-time measurements of optical diffuse reflectance and electroencephalogram (EEG were performed. Even under conditions showing no clear changes in systemic physiological parameters, the brain showed a drastic light scattering change accompanied by EEG suppression, which indicated the occurrence of spreading depression, long-lasting hypoxemia and signal change indicating mitochondrial energy impairment. Under the standard LISW conditions examined, hemorrhage and contusion were not apparent in the cortex. To investigate events associated with spreading depression, measurement of direct current (DC potential, light scattering imaging and stereomicroscopic observation of blood vessels were also conducted for the brain. After LISW application, we observed a distinct negative shift in the DC potential, which temporally coincided with the transit of a light scattering wave, showing the occurrence of spreading depolarization and concomitant change in light scattering. Blood vessels in the brain surface initially showed vasodilatation for 3-4 min, which was followed by long-lasting vasoconstriction, corresponding to hypoxemia. Computer simulation based on the inverse Monte Carlo method showed that hemoglobin oxygen saturation declined to as low as ∼35% in the long-term hypoxemic phase. Overall, we found that topical application of a shock wave to the brain caused spreading depolarization/depression and prolonged severe hypoxemia-oligemia, which might lead to pathological conditions in the brain. Although further study is needed, our findings suggest that spreading depolarization/depression is one of

  4. The effects of reboxetine treatment on depression-like behavior, brain neurotrophins, and ERK expression in rats exposed to chronic mild stress.

    Science.gov (United States)

    First, Maya; Gil-Ad, Irit; Taler, Michal; Tarasenko, Igor; Novak, Nurit; Weizman, Abraham

    2013-05-01

    Chronic mild stress (CMS) in rats is an established rodent depression model. Antidepressants attenuate the depression-like symptoms and prevent the biochemical changes caused by stress. In the present study, we examined the effect of CMS and the selective norepinephrine reuptake inhibitor (NRI) reboxetine (REB) treatment on behavioral parameters in rats and on hippocampal and cortical neurotrophic factors. Male Sprague Dawley rats were exposed for 5 weeks to a variety of mild stressors. REB (5 mg/kg/i.p.) was daily injected to half of the stressed and unstressed groups. Animal behavior following CMS was tested using the Morris Water Maze (MWM) cognitive paradigm and by monitoring sucrose intake and weight gain. After 5 weeks of CMS, stressed rats showed decreased sucrose intake, and REB treatment normalized this decrease. CMS reduced hippocampal brain-derived neurotrophic factor (BDNF) levels, and REB treatment reversed this alteration and increased BDNF receptor (TrkB) levels. REB elevated hippocampal extracellular signal-regulated kinase (ERK) phosphorylation of both stressed and unstressed rats. In conclusion, our study shows that BDNF, its receptor TrkB, and ERK participate in the neurobiological response to chronic stress and in the molecular and cellular activities of REB in the hippocampus.

  5. Changes of brain derived neurotrophic factor in hippocampus of chronic lead exposed rats%慢性染铅大鼠海马脑源性神经营养因子的改变

    Institute of Scientific and Technical Information of China (English)

    李积胜; 刘亚华; 杨峰

    2004-01-01

    Objective: To investigate the changes of brain derived neurotrophic factor(BDNF) in hippocampus of chronic lead exposed rats. Methods: Wistar rats were exposed to lead by drinking 0.02%、0.2% lead acetate solution for three months, respectively. Investigate the changes of learning and memory ability by Y-labyrinth experiment, study the changes of BDNF positive neuron in CA1, CA3 and dentate gyrus in hippocampus of rats by immunohistochemistry. Results: BDNF positive neurons distribute everywhere in the hippocampus under normal condition. Compared with the contral group, the number of BDNF positive neurons in the hippocampus subregions were decreased significantly of two different dosage (0.02%, 0.2% ) chronic lead exposed groups( P < 0. 05). Conclusion: These results suggest that the reduction of BDNF positive neuron in hippocampus might be related to the impact of lead on learning and memory.

  6. In situ expression of heat-shock proteins and 3-nitrotyrosine in brains of young rats exposed to a WiFi signal in utero and in early life.

    Science.gov (United States)

    Aït-Aïssa, Saliha; de Gannes, Florence Poulletier; Taxile, Murielle; Billaudel, Bernard; Hurtier, Annabelle; Haro, Emmanuelle; Ruffié, Gilles; Athané, Axel; Veyret, Bernard; Lagroye, Isabelle

    2013-06-01

    The bioeffects of exposure to Wireless High-Fidelity (WiFi) signals on the developing nervous systems of young rodents was investigated by assessing the in vivo and in situ expression levels of three stress markers: 3-Nitrotyrosine (3-NT), an oxidative stress marker and two heat-shock proteins (Hsp25 and Hsp70). These biomarkers were measured in the brains of young rats exposed to a 2450 MHz WiFi signal by immunohistochemistry. Pregnant rats were first exposed or sham exposed to WiFi from day 6 to day 21 of gestation. In addition three newborns per litter were further exposed up to 5 weeks old. Daily 2-h exposures were performed blind in a reverberation chamber and whole-body specific absorption rate levels were 0, 0.08, 0.4 and 4 W/kg. 3-NT and stress protein expression was assayed in different areas of the hippocampus and cortex. No significant difference was observed among exposed and sham-exposed groups. These results suggest that repeated exposure to WiFi during gestation and early life has no deleterious effects on the brains of young rats.

  7. Differential Gene Expression Patterns in Developing Sexually Dimorphic Rat Brain Regions Exposed to Antiandrogenic, Estrogenic, or Complex Endocrine

    DEFF Research Database (Denmark)

    Lichtensteiger, Walter; Bassetti-Gaille, Catherine; Faass, Oliver

    2015-01-01

    The study addressed the question whether gene expression patterns induced by different mixtures of endocrine disrupting chemicals (EDCs) administered in a higher dose range, corresponding to 450×, 200×, and 100× high-end human exposure levels, could be characterized in developing brain with respect...... to endocrine activity of mixture components, and which developmental processes were preferentially targeted. Three EDC mixtures, A-Mix (anti-androgenic mixture) with 8 antiandrogenic chemicals (di-n-butylphthalate, diethylhexylphthalate, vinclozolin, prochloraz, procymidone, linuron, epoxiconazole, and DDE), E...... on genes encoding for components of excitatory glutamatergic synapses and genes controlling migration and pathfinding of glutamatergic and GABAergic neurons, as well as genes linked with increased risk of autism spectrum disorders. Because development of glutamatergic synapses is regulated by sex steroids...

  8. Oligodendrocyte transcription factor 1 overexpression promotes oligodendrocyte transcription factor 2 expression in the brains of neonatal rats exposed to hypoxia****☆

    Institute of Scientific and Technical Information of China (English)

    Lijun Yang; Hong Cui; Aijun Yang; Wenxing Jiang

    2011-01-01

    To examine the expression profiles of oligodendrocyte transcription factors 1 and 2 (Olig1 and Olig2) and the interaction between these two proteins, Olig1 was transfected into the lateral ventricles of neonatal rats subjected to hypoxia. Immunohistochemistry demonstrated that Olig2 was expressed throughout the nuclei in the brain, and expression increased at 3 days following hypoxia and was higher than levels at 7 days following Ad5-Olig1 transfection. Western blot revealed that Olig1 and Olig2 expression increased in Olig1-transfected brain cells 3 days after hypoxia, but Olig1 and Olig2 expression decreased at 7 days. These results indicate that Olig1 overexpression enhances Olig2 expression in brain tissues of hypoxia rats.

  9. Acetylation of histones in neocortex and hippocampus of rats exposed to different modes of hypobaric hypoxia: Implications for brain hypoxic injury and tolerance.

    Science.gov (United States)

    Samoilov, Mikhail; Churilova, Anna; Gluschenko, Tatjana; Vetrovoy, Oleg; Dyuzhikova, Natalia; Rybnikova, Elena

    2016-03-01

    Acetylation of nucleosome histones results in relaxation of DNA and its availability for the transcriptional regulators, and is generally associated with the enhancement of gene expression. Although it is well known that activation of a variety of pro-adaptive genes represents a key event in the development of brain hypoxic/ischemic tolerance, the role of epigenetic mechanisms, in particular histone acetylation, in this process is still unexplored. The aim of the present study was to investigate changes in acetylation of histones in vulnerable brain neurons using original well-standardized model of hypobaric hypoxia and preconditioning-induced tolerance of the brain. Using quantitative immunohistochemistry and Western blot, effects of severe injurious hypobaric hypoxia (SH, 180mm Hg, 3h) and neuroprotective preconditioning mode (three episodes of 360mm Hg for 2h spaced at 24h) on the levels of the acetylated proteins and acetylated H3 Lys24 (H3K24ac) in the neocortex and hippocampus of rats were studied. SH caused global repression of the acetylation processes in the neocortex (layers II-III, V) and hippocampus (CA1, CA3) by 3-24h, and this effect was prevented by the preconditioning. Moreover, hypoxic preconditioning remarkably increased the acetylation of H3K24 in response to SH in the brain areas examined. The preconditioning hypoxia without subsequent SH also stimulated acetylation processes in the neocortex and hippocampus. The moderately enhanced expression of the acetylated proteins in the preconditioned rats was maintained for 24h, whereas acetylation of H3K24 was intense but transient, peaked at 3h. The novel data obtained in the present study indicate that large activation of the acetylation processes, in particular acetylation of histones might be essential for the development of brain hypoxic tolerance.

  10. Gene expression profile of brain regions reflecting aberrations in nervous system development targeting the process of neurite extension of rat offspring exposed developmentally to glycidol.

    Science.gov (United States)

    Akane, Hirotoshi; Saito, Fumiyo; Shiraki, Ayako; Imatanaka, Nobuya; Akahori, Yumi; Itahashi, Megu; Wang, Liyun; Shibutani, Makoto

    2014-12-01

    We previously found that exposure to glycidol at 1000 ppm in drinking water caused axonopathy in maternal rats and aberrations in late-stage hippocampal neurogenesis, targeting the process of neurite extension in offspring. To identify the profile of developmental neurotoxicity of glycidol, pregnant Sprague-Dawley rats were given drinking water containing glycidol from gestational day 6 until weaning on day 21 after delivery, and offspring at 0, 300 and 1000 ppm were subjected to region-specific global gene expression profiling. Four brain regions were selected to represent both cerebral and cerebellar tissues, i.e., the cingulate cortex, corpus callosum, hippocampal dentate gyrus and cerebellar vermis. Downregulated genes in the dentate gyrus were related to axonogenesis (Nfasc), myelination (Mal, Mrf and Ugt8), and cell proliferation (Aurkb and Ndc80) at ≥ 300 ppm, and upregulated genes were related to neural development (Frzb and Fzd6) at 1000 ppm. Upregulation was observed for genes related to myelination (Kl, Igf2 and Igfbp2) in the corpus callosum and axonogenesis and neuritogenesis (Efnb3, Tnc and Cd44) in the cingulate cortex, whereas downregulation was observed for genes related to synaptic transmission (Thbs2 and Ccl2) in the cerebellar vermis; all of these changes were mostly observed at 1000 ppm. Altered gene expression of Cntn3, which functions on neurite outgrowth-promotion, was observed in all four brain regions at 1000 ppm. Gene expression profiles suggest that developmental exposure to glycidol affected plasticity of neuronal networks in the broad brain areas, and dentate gyrus neurogenesis may be the sensitive target of this type of toxicity.

  11. Patterns of social-experience-related c-fos and Arc expression in the frontal cortices of rats exposed to saccharin or moderate levels of ethanol during prenatal brain development.

    Science.gov (United States)

    Hamilton, Derek A; Candelaria-Cook, Felicha T; Akers, Katherine G; Rice, James P; Maes, Levi I; Rosenberg, Martina; Valenzuela, C Fernando; Savage, Daniel D

    2010-12-01

    Recent findings from our laboratory indicate that alterations in frontal cortex function, structural plasticity, and related social behaviors are persistent consequences of exposure to moderate levels of ethanol during prenatal brain development [24]. Fetal-ethanol-related reductions in the expression of the immediate early genes (IEGs) c-fos and Arc and alterations in dendritic spine density in ventrolateral and medial aspects of frontal cortex suggest a dissociation reminiscent of that described by Kolb et al. [38] in which these aspects of frontal cortex undergo reciprocal experience-dependent changes. In addition to providing a brief review of the available data on social behavior and frontal cortex function in fetal-ethanol-exposed rats, the present paper presents novel data on social-experience-related IEG expression in four regions of frontal cortex (Zilles LO, VLO, Fr1, Fr2) that are evaluated alongside our prior data from AID and Cg3. Social experience in normal rats was related to a distinct pattern of IEG expression in ventrolateral and medial aspects of frontal cortex, with generally greater expression observed in ventrolateral frontal cortex. In contrast, weaker expression was observed in all aspects of frontal cortex in ethanol-exposed rats, with the exception of an experience-related increase in the medial agranular cortex. Behaviors related to social investigation and wrestling/boxing were differentially correlated with patterns of activity-related IEG expression in the regions under investigation for saccharin- and ethanol-exposed rats. These observations suggest that recruitment and expression of IEGs in frontal cortex following social experience are potentially important for understanding the long-term consequences of moderate prenatal ethanol exposure on frontal cortex function, synaptic plasticity, and related behaviors.

  12. Evaluation of Some Biochemical Parameters and Brain Oxidative Stress in Experimental Rats Exposed Chronically to Silver Nitrate and the Protective Role of Vitamin E and Selenium

    Science.gov (United States)

    Gueroui, Mouna; Kechrid, Zine

    2016-01-01

    Due to undesirable hazardous interactions with biological systems, this investigation was undertaken to evaluate the effect of chronic exposure to silver on certain biochemical and some oxidative stress parameters with histopathological examination of brain, as well as the possible protective role of selenium and/or vitamin E as nutritional supplements. Thirty six male rats were divided into six groups of six each: the first group used as a control group. Group II given both vitamin E (400 mg/kg) of diet and selenium (Se) (1 mg/L) in their drinking water. Group III given silver as silver nitrate (AgNO3) (20 mg/L). Group IV given vitamin E and AgNO3. Group V given both AgNO3 and selenium. Group VI given AgNO3, vitamin E and Se. The animals were in the same exposure conditions for 3 months. According to the results which have been obtained; there was an increase in serum lactate dehydrogenase (LDH), lipase activities and cholesterol level, a decrease in serum total protein, calcium and alkaline phosphatase (ALP) activity in Ag-intoxicated rats. Moreover, the findings showed that Ag+ ions affected antioxidant defense system by decreasing superoxide dismutase (SOD) activity and increasing vitamin E concentration with a high level of malondialdehyde (MDA) in brain tissue. The histological examination also exhibited some nervous tissue alterations including hemorrhage and cytoplasm vacuolization. However, the co-administration of selenium and/or vitamin E ameliorated the biochemical parameters and restored the histological alterations. In conclusion, this study indicated that silver could cause harmful effects in animal body and these effects can be more toxic in high concentrations or prolonged time exposure to this metal. However, selenium and vitamin E act as powerful antioxidants which may exercise adverse effect against the toxicity of this metal.

  13. Neurobehavioral Assessment of Rats Exposed to Yttrium Nitrate during Development

    Institute of Scientific and Technical Information of China (English)

    LI Chen Xi; MA Chuan; FANG Hai Qin; ZHI Yuan; YU Zhou; XU Hai Bin; JIA Xu Dong

    2015-01-01

    Objective The aim of this study was to assess the effects of yttrium nitrate on neurobehavioral development in Sprague-Dawley rats. Methods Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day (GD) 6 to postnatal day (PND) 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70. Results No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21;however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results. Conclusion Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.

  14. Assessment of neurotoxic effects and brain region distribution in rat offspring prenatally co-exposed to low doses of BDE-99 and methylmercury.

    Science.gov (United States)

    Zhao, Wenchang; Cheng, Jinping; Gu, Jinmin; Liu, Yuanyuan; Fujimura, Masatake; Wang, Wenhua

    2014-10-01

    Exposure to polybrominated diphenyl ether (PDBE) and methylmercury (MeHg) can occur simultaneously as both contaminants are found in the same food sources, especially fish, seafood, marine mammals and milk. The aim of this study was to assess the effects of exposure to low levels of MeHg (2.0 μg mL(-1) in drinking water) and BDE-99 (0.2 mg kg(-1) d(-1)) from gestational day 6 to postnatal day (PND) 21, alone and in combination, on neurobehavioral development and redox responses in offspring. The present study demonstrated an interaction due to co-exposure with low doses of MeHg and BDE-99 enhanced developmental neurotoxic effects. These effects were manifested as the delayed appearance of negative geotaxis reflexes, impaired motor coordination, and induction of oxidative stress in the cerebellum. In particular, the cerebellum may be a sensitive target for combined MeHg and BDE-99 toxicity. The neurotoxicity of low dose MeHg was exacerbated by the presence of low dose of BDE-99. It is concluded that prenatal co-exposure to MeHg and BDE-99 causes oxidative stress in the cerebellum of offspring by altering the activity of different antioxidant enzymes and producing free radicals. Hg retention was not affected by co-exposure to BDE-99. However, MeHg co-exposure seemed to increase BDE-99 concentrations in selected brain regions in pups compared to pups exposed to BDE-99 only. These results showed that the adverse effects following prenatal co-exposure to MeHg and BDE-99 were associated with tissue concentrations very close to the current human body burden of this persistent bioaccumulative compound.

  15. Protective Effect of Ocimum basilicum on Brain Cells Exposed to Oxidative Damage by Electromagnetic Field in Rat: Ultrastructural Study by Transmission Electron Microscopy

    OpenAIRE

    Khaki Arash

    2016-01-01

    Objective: Basil herb (Ocimum basilicum) has long been used in human nutrition. Nowadays antioxidant role of this herb is known more. The aim of this study was to study the anti-oxidative property of sweet basil to protect central nervous system against oxidative damages of electromagnetic field (EMF) and its affective sequences. Materials and Methods: Forty Albino male Wistar rats were randomly allocated to four groups, 10 rats per each. Group 1 received normal diet (control group),...

  16. Cognitive impairment and neurogenotoxic effects in rats exposed to low-intensity microwave radiation.

    Science.gov (United States)

    Deshmukh, Pravin Suryakantrao; Nasare, Namita; Megha, Kanu; Banerjee, Basu Dev; Ahmed, Rafat Sultana; Singh, Digvijay; Abegaonkar, Mahesh Pandurang; Tripathi, Ashok Kumar; Mediratta, Pramod Kumari

    2015-01-01

    The health hazard of microwave radiation (MWR) has become a recent subject of interest as a result of the enormous increase in mobile phone usage. The present study aimed to investigate the effects of chronic low-intensity microwave exposure on cognitive function, heat shock protein 70 (HSP70), and DNA damage in rat brain. Experiments were performed on male Fischer rats exposed to MWR for 180 days at 3 different frequencies, namely, 900, 1800 MHz, and 2450 MHz. Animals were divided into 4 groups: group I: sham exposed; group II: exposed to MWR at 900 MHz, specific absorption rate (SAR) 5.953 × 10(-4) W/kg; group III: exposed to 1800 MHz, SAR 5.835 × 10(-4) W/kg; and group IV: exposed to 2450 MHz, SAR 6.672 × 10(-4) W/kg. All the rats were tested for cognitive function at the end of the exposure period and were subsequently sacrificed to collect brain. Level of HSP70 was estimated by enzyme-linked immunotarget assay and DNA damage was assessed using alkaline comet assay in all the groups. The results showed declined cognitive function, elevated HSP70 level, and DNA damage in the brain of microwave-exposed animals. The results indicated that, chronic low-intensity microwave exposure in the frequency range of 900 to 2450 MHz may cause hazardous effects on the brain.

  17. Summary of high field diffusion MRI and microscopy data demonstrate microstructural aberration in chronic mild stress rat brain

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove

    2016-01-01

    Abstract This data article describes a large, high resolution diffusion MRI data set from fixed rat brain acquired at high field strength. The rat brain samples consist of21adult rat brain hemispheres from animals exposed to chronic mild stress (anhedonic and resilient) and controls. Histology from...

  18. 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.

  19. Peripheral Neuropathy in Rats Exposed to Dichloroacetate

    Science.gov (United States)

    Calcutt, Nigel A.; Lopez, Veronica L.; Bautista, Arjel D.; Mizisin, Leah M.; Torres, Brenda R.; Shroads, Albert L.; Mizisin, Andrew P.; Stacpoole, Peter W.

    2009-01-01

    The use of dichloroacetate (DCA) for treating patients with mitochondrial diseases is limited by the induction of peripheral neuropathy. The mechanisms of DCA-induced neuropathy are not known. Oral DCA treatment (50–500 mg/kg/day for up to 16 weeks) induced tactile allodynia in both juvenile and adult rats; concurrent thermal hypoalgesia developed at higher doses. Both juvenile and adult rats treated with DCA developed nerve conduction slowing that was more pronounced in adult rats. No overt axonal or glial cell abnormalities were identified in peripheral nerves or spinal cord of any DCA-treated rats but morphometric analysis identified a reduction of mean axonal caliber of peripheral nerve myelinated fibers. DCA treatment also caused accumulation of oxidative stress markers in the nerves. These data indicate that behavioral, functional and structural indices of peripheral neuropathy may be induced in both juvenile and adult rats treated with DCA at doses similar to those in clinical use. DCA-induced peripheral neuropathy primarily afflicts axons and involves both metabolic and structural disorders. The DCA-treated rat may provide insight into the pathogenesis of peripheral neuropathy and facilitate development of adjuvant therapeutics to prevent this disorder that currently restricts the clinical use of DCA. PMID:19680144

  20. Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine

    Energy Technology Data Exchange (ETDEWEB)

    Kahila, H.; Kivitie-Kallio, S.; Halmesmaki, E.; Valanne, L.; Autti, T. [Dept. of Obstetrics and Gynecology, Dept. of Pediatrics, and Helsinki Medical Imaging Center, Helsinki Univ. Central Hospital (Finland)

    2007-02-15

    Purpose: To evaluate the brains of newborns exposed to buprenorphine prenatally. Material and Methods: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. Results: Neither structural abnormalities nor abnormalities in signal intensity were recorded. Conclusion: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process.

  1. Changes in markers of oxidative stress and membrane properties in synaptosomes from rats exposed prenatally to toluene

    DEFF Research Database (Denmark)

    Edelfors, Sven; Hass, Ulla; Hougaard, Karin S.

    2002-01-01

    The present study was undertaken in order to investigate if toluene induced oxidative stress in brains from rats exposed prenatally to 1800 ppm toluene 6 hr/day at days 7-20 during the pregnancy. 35-42 days after birth the rats were killed and synaptosomal fractions were prepared...... for the experiments, Synaptosomes from rats exposed prenatally to toluene exhibited an increased level of oxidative stress when incubated with toluene in vitro compared to synaptosomes from unexposed offspring. Also the cell membrane was affected, as the calcium leakage was more increased from exposed synaptosomes...

  2. Decreased glucose transporter 1 gene expression and glucose uptake in fetal brain exposed to ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Singh, S.P.; Pullen, G.L.; Srivenugopal, K.S.; Yuan Xiaohua; Snyder, A.K. (Veterans Affairs Medical Center, North Chicago, IL (United States) Chicago Medical School, North Chicago, IL (United States))

    1992-01-01

    Using pregnant rats fed equicaloric liquid diets (AF, ad libitum-fed controls; PF, pair-fed controls; EF, ethanol-fed), the authors have previously shown that maternal alcoholism produces a specific and significant decrease of glucose in the fetal brain, which is accompanied by growth retardation. To further define the mechanisms of ethanol-induced perturbations in fetal fuel supply, they have examined (I) the uptake of 2-deoxyglucose (2-DG) by dissociated brain cells from fetal rats that were exposed to ethanol in utero and (II) the steady-state levels of the glucose transporter-1 (GT-1) mRNA. A 9% decrease in brain weight and a 54.8% reduction in 2-DG uptake into brain cells were found in offspring of EF mothers compared to the AF group. Brain weight correlated with the rate of 2-DG uptake. Northern blot analysis showed a 50% reduction of GT-1 mRNA in EF brain relative to that in the AF and PF groups. They conclude that glucose transport into the brain is an important parameter altered by maternal ethanol ingestion.

  3. Increased gluconeogenesis in rats exposed to hyper-G stress

    Science.gov (United States)

    Daligcon, B. C.; Oyama, J.; Hannak, K.

    1985-01-01

    The effect of glucogenesis on the plasma glucose and liver glycogen of rats exposed to hyper-G stress is investigated. Twelve male Sprague-Dawley rats are injected with C-14 lactate, alanine, of glycerol, and six of the rats are exposed to 3.1 G for 0.25, 0.50, and 1.0 hr. The plasma glucose and liver glycogen of the centrifuged and noncentrifuged rats are analyzed. A significant increase in the C-14 incorporation of the substrate into the plasma glucose and liver glycogen is observed in the centrifuged rats. The injection of 5-methoxyindole-2-carboxylic acid, a gluconeogenesis inhibitor, results in a blocked increase in plasma glucose and liver glycogen. The role of epinephrine on the hyperglycemic and liver glycogen responses of centrifuged rats is studied. It is concluded that the initial increase in plasma glucose and liver glycogen in rats exposed to hyper-G stress is the result of an increased rate of gluconeogenesis.

  4. Insulin Expression in Rats Exposed to Cadmium

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objectives To investigate the effects of cadmium exposure on insulin expression in rats. Methods Eighteen adult SD assessed. The levels of cadmium and zinc in pancreas, blood and urine glucose, serum insulin and urine NAG (N-acyetyl-β-glucosaminidase) were determined. The gene expressions of metallothionein (MT) and insulin were also measured,and the oral glucose tolerance tests (OGTT) were carried out. Results The contents of cadmium in pancreas in cadmium-treated rats were higher than that in the control group, which was associated with slight increase of zinc in pancreas.not change significantly after cadmium administration, and the UNAG had no change in Cd-treated group. The gene expression the change of the expression of insulin, MT-Ⅰ and MT-Ⅱ genes. Cadmium can influence the biosynthesis of insulin, but does not induce the release of insulin. The dysfunction of pancreas occurs earlier than that of kidney after administration of cadmium.

  5. BIOLOGICAL EFFECTS OF MICROWAVE RADIATION ON BRAIN TISSUE IN RATS

    Directory of Open Access Journals (Sweden)

    Boris Đinđić

    2003-04-01

    Full Text Available Exposure to microwave radiation induces multiple organ dysfunctions, especially in CNS.The aim of this work was investigation of biological effects of microwave radiation on rats' brain and determination of increased oxidative stress as a possible pathogenetic's mechanism.Wis tar rats 3 months old were divided in experimental (4 female and 4 male animal and control group (5 female and 4 male. This experimental group was constantly exposed to a magnetic field of 5 mG. We simulated using of mobile phones 30 min every day. The source of NIR emitted MF that was similar to mobile phones at 900 MHz. The rats were killed after 2 months. Biological effects were determined by observation of individual and collective behavior and body mass changes. Lipid per oxidation was determined by measuring quantity of malondialdehyde (MDA in brain homogenate.The animals in experimental group exposed to EMF showed les weight gain. The most important observations were changing of basic behavior models and expression of aggressive or panic behavior. The content of MDA in brain tissue is singificantly higher (1.42 times in rats exposed to electromagnetic fields (3,82±0.65 vs. control 2.69±0.42 nmol/mg proteins, p<0.01.Increased oxidative stress and lipid peroxidation after exposition in EM fields induced disorders of function and structure of brain.

  6. Effect of basic fibroblast growth factor and danshen on bcl-2 and p53 mRNA expression in the brain of rats exposed to repeated,high,positive acceleration(+Gz)

    Institute of Scientific and Technical Information of China (English)

    Hongjin Liu; Qing Cai

    2008-01-01

    -transcription polymerase chain reaction.Apoptotic cell death was detected by terminal deoxvnuleotidyl transferase-mediated dUTP nick end labeling.RESULTS:Changes in mRNA expression of bcl-2 and p53 and apoptotic cells were observed in rat brain six hours after repeated+Gz cxposurcs.bFGF and danshen were able block the changes of bcl-2 and p53 expression and inhibit apoptotic cell death.CONCLUSION:The data suggest that apoptosis and changes in bcl-2 and p53 expression in the rat brain can be induced by repeated+Gz exposures.Apoptosis is,therefore,one of the molecular mechanisms of brain damage induced by repeated+Gz exposures.bFGF and danshen were of the equal potency in preventing brain injury induced by repeated+Gz exposures.

  7. Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate

    Institute of Scientific and Technical Information of China (English)

    Mohammad Shahandeh; Valiollah Dabidi Roshan; Somayeh Hosseinzadeh; Soleiman Mahjoub; Vaginak Sarkisian

    2013-01-01

    After intraperitoneal injection of 20 mg/kg lead acetate, rats received 8 weeks of treadmill exercise (15–22 m/min, 25–64 minutes) and/or treadmill exercise at 1.6 km/h until exhaustion. The markers related to neurotoxicity were measured by enzyme-linked immunosorbent assay method. 8 weeks of treadmill exercise significantly increased brain-derived neurotrophic factor level in the hippocampus (P = 0.04) and plasma level of total antioxidant capacity of rats exposed to lead acetate (P < 0.001), and significantly decreased plasma level of malondialdehyde (P < 0.001). Acute exercise only decreased the hippocampal malondialdehyde level (P = 0.09) and increased brain-derived neurotrophic factor level in the hippocampus (P = 0.66). Acute exercise also enhanced the total antioxidant capacity in rats exposed to lead acetate, insignificantly (P = 0.99). These findings suggest that chronic treadmill exercise can significantly decrease neurotoxicity and alleviate oxidative stress in rats exposed to lead acetate. However, acute endurance exercise was not associated with these beneficial effects.

  8. Zinc supplementation ameliorates electromagnetic field-induced lipid peroxidation in the rat brain.

    Science.gov (United States)

    Bediz, Cem Seref; Baltaci, Abdulkerim Kasim; Mogulkoc, Rasim; Oztekin, Esma

    2006-02-01

    Extremely low-frequency (0-300 Hz) electromagnetic fields (EMFs) generated by power lines, wiring and home appliances are ubiquitous in our environment. All populations are now exposed to EMF, and exposure to EMF may pose health risks. Some of the adverse health effects of EMF exposure are lipid peroxidation and cell damage in various tissues. This study has investigated the effects of EMF exposure and zinc administration on lipid peroxidation in the rat brain. Twenty-four male Sprague-Dawley rats were randomly allocated to three groups; they were maintained untreated for 6 months (control, n = 8), exposed to low-frequency (50 Hz) EMF for 5 minutes every other day for 6 months (n = 8), or exposed to EMF and received zinc sulfate daily (3 mg/kg/day) intraperitoneally (n = 8). We measured plasma levels of zinc and thiobarbituric acid reactive substances (TBARS), and levels of reduced glutathione (GSH) in erythrocytes. TBARS and GSH levels were also determined in the brain tissues. TBARS levels in the plasma and brain tissues were higher in EMF-exposed rats with or without zinc supplementation, than those in controls (p < 0.001). In addition, TBARS levels were significantly lower in the zinc-supplemented rats than those in the EMF-exposed rats (p < 0.001). GSH levels were significantly decreased in the brain and erythrocytes of the EMF-exposed rats (p < 0.01), and were highest in the zinc-supplemented rats (p < 0.001). Plasma zinc was significantly lower in the EMF-exposed rats than those in controls (p < 0.001), while it was highest in the zinc-supplemented rats (p < 0.001). The present study suggests that long-term exposure to low-frequency EMF increases lipid peroxidation in the brain, which may be ameliorated by zinc supplementation.

  9. Spatial learning, monoamines and oxidative stress in rats exposed to 900 MHz electromagnetic field in combination with iron overload.

    Science.gov (United States)

    Maaroufi, Karima; Had-Aissouni, Laurence; Melon, Christophe; Sakly, Mohsen; Abdelmelek, Hafedh; Poucet, Bruno; Save, Etienne

    2014-01-01

    The increasing use of mobile phone technology over the last decade raises concerns about the impact of high frequency electromagnetic fields (EMF) on health. More recently, a link between EMF, iron overload in the brain and neurodegenerative disorders including Parkinson's and Alzheimer's diseases has been suggested. Co-exposure to EMF and brain iron overload may have a greater impact on brain tissues and cognitive processes than each treatment by itself. To examine this hypothesis, Long-Evans rats submitted to 900 MHz exposure or combined 900 MHz EMF and iron overload treatments were tested in various spatial learning tasks (navigation task in the Morris water maze, working memory task in the radial-arm maze, and object exploration task involving spatial and non spatial processing). Biogenic monoamines and metabolites (dopamine, serotonin) and oxidative stress were measured. Rats exposed to EMF were impaired in the object exploration task but not in the navigation and working memory tasks. They also showed alterations of monoamine content in several brain areas but mainly in the hippocampus. Rats that received combined treatment did not show greater behavioral and neurochemical deficits than EMF-exposed rats. None of the two treatments produced global oxidative stress. These results show that there is an impact of EMF on the brain and cognitive processes but this impact is revealed only in a task exploiting spontaneous exploratory activity. In contrast, there are no synergistic effects between EMF and a high content of iron in the brain.

  10. Antioxidant status in MgO nanoparticle-exposed rats.

    Science.gov (United States)

    Kiranmai, G; Reddy, A Rama Narsimha

    2013-11-01

    In this present study, antioxidant status was evaluated in rat serum following exposure to magnesium oxide (MgO) nanoparticles. The lungs of rats were intratracheally instilled with (single dose) phosphate-buffered saline (PBS) + 1% of Tween 80 (solvent control) or MgO or carbonyl iron (negative control) or quartz particles (positive control) at a dose of 1 and 5 mg/kg of body weight. The blood samples were collected at 1, 7, and 30 days of postinstillation of nanoparticles after their exposure, and different parameters were estimated to assess the oxidative stress induced by the instillation of MgO. Exposure of rats to MgO produced a significant (p MgO nanoparticle-exposed rats indicates the reduction in antioxidant defense mechanisms due to the instillation of MgO. These results indicate that exposure to MgO nanoparticles induces oxidative stress by reducing the total antioxidant capacity in rats. The findings suggest possible occupational health hazard in chronic exposures.

  11. P300 brain potential among workers exposed to organic solvents

    Directory of Open Access Journals (Sweden)

    Bente E. Moen

    2009-10-01

    Full Text Available  SUMMARYThe P300 component of the auditory event-related brain potential was examined in a group of 11workers exposed to low levels of organic solvents in a paint factory and 11 unexposed controls beforeand after 3 weeks of summer vacation. The P300 latency time was found to be prolonged among theexposed workers compared to the reference group before the summer vacation, and to be significantlylonger before the vacation than after in the exposed group.The P300 component was also examined in a group of 85 seamen from chemical tankers, experiencingpeak exposures to organic solvents. They were compared to a reference group of unexposedseamen. Comparing these two groups, no difference was found in the P300 latency time. No relationshipbetween the P300 latency time and exposure was found in a multiple regression analysis, includingthe variables age, alcohol consumption, smoking and cerebral concussions.The study indicates the occurrence of an acute biological effect in the nervous system related toorganic solvent exposure, expressed by prolonged P300 latency time. This was found at very lowexposure levels and should be studied further.

  12. In utero exposure to microwave radiation and rat brain development.

    Science.gov (United States)

    Merritt, J H; Hardy, K A; Chamness, A F

    1984-01-01

    Timed-pregnancy rats were exposed in a circular waveguide system starting on day 2 of gestation. The system operated at 2,450 MHz (pulsed waves; 8 microseconds PW; 830 pps). Specific absorption rate (SAR) was maintained at 0.4 W/kg by increasing the input power as the animals grew in size. On day 18 of gestation the dams were removed from the waveguide cages and euthanized; the fetuses were removed and weighed. Fetal brains were excised and weighed, and brain RNA, DNA and protein were determined. Values for measured parameters of the radiated fetuses did not differ significantly from those of sham-exposed fetuses. A regression of brain weight on body weight showed no micrencephalous fetuses in the radiation group when using as a criterion a regression line based on two standard errors of the estimate of the sham-exposed group. In addition, metrics derived from brain DNA (ie, cell number and cell size) showed no significant differences when radiation was compared to sham exposure. We conclude that 2,450-MHz microwave radiation, at an SAR of 0.4 W/kg, did not produce significant alterations in brain organogenesis.

  13. Behaviour-toxicological studies in rats exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Wurms, F.

    1979-01-01

    Studies were carried out on a behaviour-toxicological animal model in order to find out whether Cd may induce a minimal cerebral dysfunction and whether this effect outlasts prenatal and neonatal exposure. For this purpose, pregnant Wistar rats were given daily s.c. injections of 0.15 mg Cd/kg for a period of 50 d until weaning of the young rats at the age of 4 weeks. The male offspring were either given no Cd until the age of 100 d when the tests were started (A-group), or they were given daily s.c. injections of the above dose (B-group). The third group consisted of NaCl-injected control animals of the same age. The behaviour-toxicological tests were carried out in a Lashley test bench, a swimming labyrinth, and an open field test under blind conditions. Cd concentrations measured in the brain, liver and kidneys at different times during the investigation showed that the placenta-brain barrier or blood-brain barrier was not fully efficient under the experimental conditions. Cd concentrations in neonates were 2.5 times higher in the brain and 5 times higher in the liver and kidneys than in control animals. In both Cd groups, visual discrimination was impaired. In the swimming labyrinth and open field test, significant changes were observed only in B-group rats. Impaired visual differentiation was observed in both groups. However, it is impossible at the present stage of investigation to decide whether the direct Cd lesions are the only cause of these behaviour-toxicological effects.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-03-01

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

  15. Developmental changes in content of glial marker proteins in rats exposed to protein malnutrition.

    Science.gov (United States)

    Feoli, Ana Maria; Leite, Marina C; Tramontina, Ana Carolina; Tramontina, Francine; Posser, Thais; Rodrigues, Letícia; Swarowsky, Alessandra; Quincozes-Santos, André; Leal, Rodrigo B; Gottfried, Carmem; Perry, Marcos Luiz; Gonçalves, Carlos-Alberto

    2008-01-02

    Pre- and postnatal protein malnutrition (PMN) adversely affects the developing brain in numerous ways, but only a few studies have investigated specific glial parameters. This study aimed to evaluate specific glial changes of rats exposed to pre and postnatal PMN, based on glial fibrillary acidic protein (GFAP) and S100B immunocontents as well as glutamine synthetase (GS), in cerebral cortex, hippocampus, cerebellum and cerebrospinal fluid, on the 2nd, 15th and 60th postnatal days. We found increases in GFAP, S100B and GS in the cerebral cortex at birth, suggesting an astrogliosis. Hippocampus and cerebellum also exhibited this profile at birth. However, a significant interaction between age and diet in postnatal life was observed only in the S100B of the cerebral cortex. No changes in the content of GFAP and S100B and GS activity were found on the 60th postnatal day in malnourished rats. In contrast, following an increase in the levels of S100B in the cerebrospinal fluid, during the early developmental stages, levels remained elevated on the 60th postnatal day. Our data support the concept of astrogliosis at birth, induced by PMN, and involve extracellular-regulated kinase activation. Specific alterations in cerebral cortex emphasize the regional vulnerability of the brain to malnutrition; some alterations were observed only at birth (e.g. GFAP); others were observed on the 2nd and 15th post-natal days (e.g. ERK phosphorylation). Taken together, transient and persistent alterations (e.g. elevated extracellular levels of S100B) suggest some brain damage or a risk of brain diseases in rats exposed to PMN.

  16. Change of Brain Cellular Mitochondrial Function and Ultrastructure in Offspring Rats Exposed to Arsenic during Gestation and Growth%胚胎期和生长期子代大鼠砷暴露对脑细胞线粒体功能和超微结构的影响

    Institute of Scientific and Technical Information of China (English)

    朱筑霞; 吴泽江; 王旭东; 易必达; 潘玮炜

    2011-01-01

    目的 观察胚胎期和生长期连续砷暴露的仔鼠脑神经细胞线粒体功能和超微结构的变化,探讨砷对子代大鼠脑功能损伤机制.方法 SD大鼠随机分成对照组、低、高砷染毒组,染砷组自由饮用As2O3水溶液,剂量为0.6、15 mg/kg,6周后,各组分别雄雌2∶1合笼产仔,仔鼠由各自染砷母代乳养至断乳后,仔鼠离开母鼠继续本组剂量染砷到6和16周,测定仔鼠脑神经细胞线粒体的呼吸活性和ATP合成量,同时观察线粒体的超微结构变化.结果 断乳后继续染砷6和16周的高、低剂量组仔鼠脑细胞线粒体Ⅲ态呼吸(R3)比对照组明显降低,以高剂量组仔鼠最为显著(P<0.01);呼吸控制率(RCR)在各染砷组都有所降低,但以16周高剂量组仔鼠降低更显著(P<0.05).染砷组的ATP合成量比对照组明显减少,以高砷组仔鼠减少更显著(P<0.01);电镜下染砷组线粒体有基质肿胀,部分嵴减少甚至断裂,高砷组仔鼠还见线粒体外膜断裂,部分线粒体呈空泡样改变,有的甚至溶解.结论 仔鼠在胚胎期与生长发育期连续砷暴露其脑神经细胞线粒体呼吸功能和能量代谢功能均会受到明显损伤,损伤程度有剂量和时间-效应关系.%Objective To investigate the toxic effects of arsenic on brain nerve cellular mitochondrial funct1on and ultrastructure of Fl generation rats exposed to arsenic during gestation and growth. Methods Sprague-Dawley(SD) rats of cleanliness grade were randomly divided into three group (low-, high-dose arsenic group and control group ), treated with arsenic (As2O3) at doses of 10 mg/kg, 0.4 mg/kg, the control group with distilled water, for 6 consecutive weeks. Fl pup rats were lactated by dam exposed arsenic until weaning, Fl pup rats continuously exposed to arsenic for 6 and 16 weeks after weaning respectively. The respiratory activity and ATP amounts of brain cellular mitochondria were determined in all groups and mitochondria

  17. ALTERATIONS IN THE ACETYLCHOLINESTERASE ACTIVITY IN THE BRAIN OF ALBINO MICE EXPOSED TO ACEPHATE

    Directory of Open Access Journals (Sweden)

    M. SIVA PRASAD

    2013-01-01

    Full Text Available Acephate (AP, a widely available organophosphorus (OP insecticide, has low mammalian toxicity and isconsidered non-phytotoxic on many crop plants and therefore it is preferred in agricultural crops. In plants andinsects, AP is metabolized extensively to methamidophos (MP, a more potent OP insecticide. The limitedmammalian metabolism of AP to MP has been studied in laboratory rat models and suggests that initial formationof MP from AP may inhibit further formation. Hence in the present investigation we have studied the effect of anAP in cholinergic mechanisms in the different regions of brain. For the present study the male mice were exposedto 1/10th LD50 of AP via oral gavage (i.e. 40.5mg/kg body weight. Our results indicate a steady decline of AChEactivity in all the regions of the brain of Acephate exposed animals. As expected an increase in ACh activity wasnoticed in all the regions of the AP exposed animals. We suggest that cholinergic system is seriously affected bythe intoxication of Acephate and the effect was more effective in 30 days when compared to 10 days

  18. Influence of Panax ginseng on the offspring of adult rats exposed to prenatal stress

    Science.gov (United States)

    KIM, YOUNG OCK; LEE, HWA-YOUNG; WON, HANSOL; NAH, SEONG-SU; LEE, HWA-YOUNG; KIM, HYUNG-KI; KWON, JUN-TACK; KIM, HAK-JAE

    2015-01-01

    The exposure of pregnant females to stress during a critical period of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. Schizophrenia is a group of common mental disorders of unclear origin, affecting approximately 1% of the global population, showing a generally young age at onset. In the present study, a repeated variable stress paradigm was applied to pregnant rats during the final week of gestation. The effects of an extract of Panax ginseng C.A. Meyer (PG) on rats exposed to prenatal stress (PNS) were investigated in terms of behavioral activity and protein expression analyses. In the behavioral tests, grooming behavior in a social interaction test, line-crossing behavior in an open-field test and swimming activity in a forced-swim test were decreased in the rats exposed to PNS compared with the non-stressed offspring; the changes in behavioral activity were reversed upon oral treatment with PG (300 mg/kg). Subsequently, western blot analysis and immunohistochemical analyses of the prefrontal cortex and hippocampus revealed that the downregulation of several neurodevelopmental genes which occurred following exposure to PNS was reversed upon treatment with PG. The current findings demonstrate that the downregulation of several genes following exposure to PNS may affect subsequent behavioral changes, and that these phenomena are reversed following treatment with PG during pregnancy. Our results suggest that oral treatment with PG reduces the incidence of psychiatric disorders, such as schizophrenia. PMID:25394395

  19. Serotonin transporter occupancy in rats exposed to serotonin reuptake inhibitors in utero or via breast milk.

    Science.gov (United States)

    Capello, Catherine F; Bourke, Chase H; Ritchie, James C; Stowe, Zachary N; Newport, D Jeffrey; Nemeroff, Amanda; Owens, Michael J

    2011-10-01

    Rigorous data regarding fetal central nervous system (CNS) exposure after antidepressant exposure are sparse. The magnitude of serotonin reuptake inhibitor (SRI) CNS exposure was measured in three groups of rats using ex vivo autoradiography of the serotonin transporter (SERT): 1) in utero, 2) postnatal clearance after birth, and 3) exposure through lactation. Rats were exposed to one of five SRI-type antidepressants (escitalopram, fluoxetine, paroxetine, sertraline, and venlafaxine) administered continuously via osmotic minipumps to pregnant or nursing dams. Dam dosing was adjusted to reflect the 50th and 85th percentiles of serum concentrations observed in pregnant women. Embryonic day 21 rat pups exposed in utero exhibited >80% SERT occupancy in brain tissue, which is equivalent to that of the pregnant dam and similar to that reported for human pharmacotherapy. Venlafaxine was the exception with occupancies ranging from 61 to 92% across different litters. The magnitude of SERT occupancy is essentially equivalent between dams and fetuses. By postnatal day 4, high SERT occupancy was observed only in fluoxetine-exposed pups (41-92% occupancy). Significantly less, but measurable, exposure occurred via breast milk exposure even in the absence of detectable drug concentrations in nursing pup sera. Pups exposed to SRIs via breast milk for 3 or 7 days exhibited varying SERT occupancies (0-57% depending on the individual medication and dam dose). These data highlight the need for animal modeling of fetal and nursing infant drug exposure using clinically meaningful dosing strategies and appropriate CNS measures to develop rational treatment guidelines that systematically minimize fetal and neonatal medication exposure in humans.

  20. Biochemical changes in the central nervous system of rats exposed to 1-bromopropane for seven days.

    Science.gov (United States)

    Wang, Hailan; Ichihara, Gaku; Ito, Hidenori; Kato, Kanefusa; Kitoh, Junzoh; Yamada, Tetsuya; Yu, Xiaozhong; Tsuboi, Seiji; Moriyama, Yoshinori; Sakatani, Rie; Shibata, Eiji; Kamijima, Michihiro; Itohara, Seiichiro; Takeuchi, Yasuhiro

    2002-05-01

    1-Bromopropane is used widely as an alternative to ozone-depleting solvents. The neurotoxic effects of this agent have been described in humans and experimental animals. Here we investigated the underlying mechanisms of the neurotoxic effects of 1-bromopropane by examining the initial biochemical changes in the central nervous system. Four groups of 9 Wistar male rats each were exposed to 200, 400, or 800 ppm 1-bromopropane or only fresh air, 8 h per day for 7 days. At the end of the experiment, the cerebrum, cerebellum, brain stem and lumbar enlargement of the spinal cord were dissected out from each rat (n = 8) for biochemical analyses. Morphological examinations of the nervous system were performed in the remaining rat of each group. 1-Bromopropane dose-dependently decreased neurospecific gamma-enolase, total glutathione, and nonprotein sulfhydryl groups in the cerebrum and cerebellum. Creatine kinase activity decreased dose-dependently in the brain and spinal cord. Histopathological examination showed swelling of preterminal axons in gracile nucleus and degeneration of myelin in peripheral nerves. Our results of low levels of gamma-enolase suggested that 1-bromopropane might primarily cause functional or cellular loss of neurons in the cerebrum and cerebellum. Glutathione depletion or modification to functional proteins containing a sulfhydryl base as a critical site might be the underlying mechanism of 1-bromopropane neurotoxicity.

  1. In vivo imaging of scattering and absorption properties of exposed brain using a digital red-green-blue camera

    Science.gov (United States)

    Nishidate, Izumi; Yoshida, Keiichiro; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu

    2014-03-01

    We investigate a method to estimate the spectral images of reduced scattering coefficients and the absorption coefficients of in vivo exposed brain tissues in the range from visible to near-infrared wavelength (500-760 nm) based on diffuse reflectance spectroscopy using a digital RGB camera. In the proposed method, the multi-spectral reflectance images of in vivo exposed brain are reconstructed from the digital red, green blue images using the Wiener estimation algorithm. The Monte Carlo simulation-based multiple regression analysis for the absorbance spectra is then used to specify the absorption and scattering parameters of brain tissue. In this analysis, the concentration of oxygenated hemoglobin and that of deoxygenated hemoglobin are estimated as the absorption parameters whereas the scattering amplitude a and the scattering power b in the expression of μs'=aλ-b as the scattering parameters, respectively. The spectra of absorption and reduced scattering coefficients are reconstructed from the absorption and scattering parameters, and finally, the spectral images of absorption and reduced scattering coefficients are estimated. The estimated images of absorption coefficients were dominated by the spectral characteristics of hemoglobin. The estimated spectral images of reduced scattering coefficients showed a broad scattering spectrum, exhibiting larger magnitude at shorter wavelengths, corresponding to the typical spectrum of brain tissue published in the literature. In vivo experiments with exposed brain of rats during CSD confirmed the possibility of the method to evaluate both hemodynamics and changes in tissue morphology due to electrical depolarization.

  2. Oxytocin biotransformation in the rat limbic brain

    NARCIS (Netherlands)

    Burbach, J.P.H.; Schotman, P.; Kloet, E.R. de

    2006-01-01

    Two peptide fragments of oxytocin were isolated by high-pressure liquid chromatography from digests of oxytocin obtained after exposure to a SPM preparation of the rat limbic brain. The structures of these peptides, being Gln-Asn-Cys(O)x-Pro-Leu-GlyNH2 and Gln-Asn-Cys(-S-S-Cys)-Pro-Leu-GlyNH2, were

  3. Neuroglobin in the rat brain: localization

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Allen, Gregg C; Nyengaard, Jens Randel

    2008-01-01

    in the rat brain using immunohistochemistry, in situ hybridization, and quantitative real-time PCR (qRT-PCR). This revealed the interesting finding that Ngb expression is restricted to a few neurone populations, many of which are involved in the sleep-wake cycle, circadian regulation or food regulation...

  4. Phosphoproteomic analysis reveals compensatory effects in the piriform cortex of VX nerve agent exposed rats.

    Science.gov (United States)

    Nirujogi, Raja Sekhar; Wright, James D; Manda, Srikanth S; Zhong, Jun; Na, Chan Hyun; Meyerhoff, James; Benton, Bernard; Jabbour, Rabih; Willis, Kristen; Kim, Min-Sik; Pandey, Akhilesh; Sekowski, Jennifer W

    2015-01-01

    To gain insights into the toxicity induced by the nerve agent VX, an MS-based phosphoproteomic analysis was carried out on the piriform cortex region of brains from VX-treated rats. Using isobaric tag based TMT labeling followed by titanium dioxide enrichment strategy, we identified 9975 unique phosphosites derived from 3287 phosphoproteins. Temporal changes in the phosphorylation status of peptides were observed over a time period of 24 h in rats exposed to a 1× LD50, intravenous (i.v.) dose with the most notable changes occurring at the 1 h postexposure time point. Five major functional classes of proteins exhibited changes in their phosphorylation status: (i) ion channels/transporters, including ATPases, (ii) kinases/phosphatases, (iii) GTPases, (iv) structural proteins, and (v) transcriptional regulatory proteins. This study is the first quantitative phosphoproteomic analysis of VX toxicity in the brain. Understanding the toxicity and compensatory signaling mechanisms will improve the understanding of the complex toxicity of VX in the brain and aid in the elucidation of novel molecular targets that would be important for development of improved countermeasures. All MS data have been deposited in the ProteomeXchange with identifier PXD001184 (http://proteomecentral.proteomexchange.org/dataset/PXD001184).

  5. Thioredoxin and impaired spatial learning and memory in the rats exposed to intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    YANG Xiu-hong; LIU Hui-guo; LIU Xue; CHEN Jun-nan

    2012-01-01

    Background Obstructive sleep apnea (OSA) can cause cognitive dysfunction and may be a reversible cause of cognitive loss in patients with Alzheimer's disease (AD).Chronic exposure to intermittent hypoxia (IH),such as encountered in OSA,is marked by neurodegenerative changes in rat brain.We investigated the change of thioredoxin (Trx),spatial learning and memory in rats exposed to chronic intermittent hypoxia (CIH).Methods Forty healthy male Sprague-Dawley (SD) rats were randomly divided into four groups of ten each:a CIH+normal saline (CIH+NS group),a N-acetylcystein-treated CIH (CIH+NAC) group,a sham CIH group (sham CIH+NS),and a sham NAC-treated sham CIH (CIH+NAC) group.Spatial learning and memory in each group was assessed with the Morris water maze.Real-time PCR and Western blotting were used to examine mRNA and protein expression of Trx in the hippocampus tissue.The terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling (TUNEL) method was used to detect the apoptotic cells of the hippocampus CA1 region.Results ClH-rats showed impaired spatial learning and memory in the Morris water maze,including longer mean latencies for the target platform,reduced numbers of passes over the previous target platform and a smaller percentage of time spent in the target quadrant.Trx mRNA and protein levels were significantly decreased in the CIH-hippocampus,meanwhile,an elevated apoptotic index revealed apoptosis of hippocampal neurons of rats exposed to CIH.The rats,which acted better in the Morris water maze,showed higher levels of the Trx mRNA and protein in the hippocampus;apoptotic index of the neurons in the hippocampus of each group was negatively correlated with the Trx mRNA and protein levels.Conclusion The Trx deficit likely plays an important role in the impaired spatial learning and memory in the rats exposed to CIH and may work through the apoptosis of neurons in the hippocampus.

  6. Protective effects of melatonin on the ionizing radiation induced DNA damage in the rat brain.

    Science.gov (United States)

    Undeger, Ulko; Giray, Belma; Zorlu, A Faruk; Oge, Kamil; Baçaran, Nurçen

    2004-03-01

    Melatonin is an endogenously produced antioxidant with radioprotective actions while ionizing radiation is a well-known cytotoxic and mutagenic agent of which the biological results are attributable to its free radical producing effects. The effect of melatonin on the DNA strand breakage and lipid peroxidation induced by ionizing radiation in the rat brain were investigated in order to clarify its radioprotective ability. The DNA strand breakage in rat brain exposed to 1000 cGy ionizing radiation was assessed by alkaline single cell gel electrophoresis and the lipid peroxidation was evaluated by measuring thiobarbituric acid reactive substances (TBARS) concentrations. A significant increase in DNA damage (p radiation treated rat brain. Pre-treatment of rats with intraperitoneal doses of 100 mg/kg melatonin provided a significant decrease in the DNA strand breakage and lipid peroxidation. Our results indicate that melatonin can protect brain cells from oxidative damage induced by ionizing radiation.

  7. Summary of high field diffusion MRI and microscopy data demonstrate microstructural aberration in chronic mild stress rat brain

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove

    2016-01-01

    Abstract This data article describes a large, high resolution diffusion MRI data set from fixed rat brain acquired at high field strength. The rat brain samples consist of21adult rat brain hemispheres from animals exposed to chronic mild stress (anhedonic and resilient) and controls. Histology from...... amygdala of the same brain hemispheres is also included with three different stains: DiI and Hoechst stained microscopic images (confocal microscopy) andALDH1L1 antibody based immunohistochemistry.These stains may be used to evaluate neurite density (DiI), nuclear density (Hoechst) and astrocytic density...

  8. 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.

  9. Exposing orgasm in the brain : a critical eye

    NARCIS (Netherlands)

    Georgiadis, Janniko R.

    2011-01-01

    There is nothing legal that comes close to orgasm, pleasure-wise. Yet very little is known about the brain mechanisms responsible for this extraordinary experience. In the last decade some progress has been made thanks to medical scanners that can be used to measure brain activity in healthy subject

  10. Memory and Brain Volume in Adults Prenatally Exposed to Alcohol

    Science.gov (United States)

    Coles, Claire D.; Goldstein, Felicia C.; Lynch, Mary Ellen; Chen, Xiangchuan; Kable, Julie A.; Johnson, Katrina C.; Hu, Xiaoping

    2011-01-01

    The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n = 26; Alcohol-related Neurodevelopmental Disorder, n = 36; and Dysmorphic, n = 30) were imaged using structural MRI with brain volume calculated for…

  11. Effects of delta9-tetrahydrocannabinol on reward and anxiety in rats exposed to chronic unpredictable stress.

    Science.gov (United States)

    Fokos, S; Panagis, G

    2010-05-01

    Although cannabis derivatives produce clear subjective motivational responses in humans leading to drug-seeking behaviour, the reinforcing attributes of these subjective effects are difficult to define in experimental animals. The aim of this study was to examine how exposure to chronic unpredictable stress (CUS) will affect reward function and anxiety after acute administration of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in rats. Male rats were exposed to either 10 days of CUS or no stressor. Alterations in brain reward function were assessed with the intracranial self-stimulation (ICSS) paradigm, and anxiety responses were measured with the elevated plus maze. CUS did not affect baseline brain stimulation reward thresholds. Delta(9)-THC did not exhibit reinforcing actions in the ICSS paradigm neither in nonstressed nor in stressed animals. More importantly, in nonstressed animals, both the low and the high dose of Delta(9)-THC exerted anxiolytic-like effects. In stressed animals, however, only the high dose of THC induced an anxiolytic-like response, whereas the low dose induced anxiogenic effects. The present results provide clear evidence for an anxiolytic effect of Delta(9)-THC both in stressed and in nonstressed animals, and indicate that environmental conditions, such as stressful experiences, do not alter the behavioural effects of Delta( 9)-THC in the ICSS paradigm.

  12. PREDICTION OF SPECIFIC DAMAGE OR INFARCTION FROM THE MEASUREMENT OF TISSUE IMPEDANCE FOLLOWING REPETITIVE BRAIN ISCHEMIA IN THE RAT

    NARCIS (Netherlands)

    KLEIN, HC; KROPVANGASTEL, W; GO, KG; KORF, J

    The development of irreversible brain damage during repetitive periods of hypoxia and normoxia was studied in anaesthetized rats with unilateral occlusion of the carotid artery (modified Levine model). Rats were exposed to 10 min hypoxia and normoxia until severe damage developed. As indices of

  13. Changes of cell factor in bronchoalveolar lavage fluid in rats exposed to silica

    Institute of Scientific and Technical Information of China (English)

    张玮

    2014-01-01

    Objective To investigate the changes in the levels of inflammatory cytokines in bronchoalveolar lavage fluid(BALF)in rats exposed to silica dust.Methods Experimental rats were randomly divided into control group and three experimental groups(doses of dust:15,30,and 60mg/ml),with 42 rats in each group.Each rat in the control group was treated with 1 ml of normal saline by intratracheal instillation,while each rat in the experimental groups was exposed to 1

  14. [Rat brain cells containing ezrin (cytovillin)].

    Science.gov (United States)

    Korzhevskiĭ, D E; Kirik, O V; Giliarov, A V

    2011-01-01

    Ezrin (cytovillin or p81 protein) is an actin-binding protein, a member of ERM (ezrin, radixin and moesin) family, which species contribute to stabilization of the plasma membrane-formed structures. The aim of the present study was to demonstrate the ezrin-containing cells in the rat brain and to describe their topography and morphological features. The most pronounced immunohistochemical reaction to ezrin was found in the epithelium of the choroid plexus, cells of the subcommissural organ and ventricular ependyma. Moreover, ezrin staining was also detected in the unidentifiable cells in the subventricular zone, rostral migration pathway and astrocytes in various brain areas. Preferential ezrin localization in the brain cells contributing to formation of barrier structures suggests its involvement in transport processes in the CNS.

  15. Low intensity microwave radiation induced oxidative stress, inflammatory response and DNA damage in rat brain.

    Science.gov (United States)

    Megha, Kanu; Deshmukh, Pravin Suryakantrao; Banerjee, Basu Dev; Tripathi, Ashok Kumar; Ahmed, Rafat; Abegaonkar, Mahesh Pandurang

    2015-12-01

    Over the past decade people have been constantly exposed to microwave radiation mainly from wireless communication devices used in day to day life. Therefore, the concerns over potential adverse effects of microwave radiation on human health are increasing. Until now no study has been proposed to investigate the underlying causes of genotoxic effects induced by low intensity microwave exposure. Thus, the present study was undertaken to determine the influence of low intensity microwave radiation on oxidative stress, inflammatory response and DNA damage in rat brain. The study was carried out on 24 male Fischer 344 rats, randomly divided into four groups (n=6 in each group): group I consisted of sham exposed (control) rats, group II-IV consisted of rats exposed to microwave radiation at frequencies 900, 1800 and 2450 MHz, specific absorption rates (SARs) 0.59, 0.58 and 0.66 mW/kg, respectively in gigahertz transverse electromagnetic (GTEM) cell for 60 days (2h/day, 5 days/week). Rats were sacrificed and decapitated to isolate hippocampus at the end of the exposure duration. Low intensity microwave exposure resulted in a frequency dependent significant increase in oxidative stress markers viz. malondialdehyde (MDA), protein carbonyl (PCO) and catalase (CAT) in microwave exposed groups in comparison to sham exposed group (pmicrowave exposed groups (pmicrowave exposed animal (pmicrowave exposed groups as compared to their corresponding values in sham exposed group (pmicrowave radiation induces oxidative stress, inflammatory response and DNA damage in brain by exerting a frequency dependent effect. The study also indicates that increased oxidative stress and inflammatory response might be the factors involved in DNA damage following low intensity microwave exposure.

  16. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenlie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ichihara, Sahoko [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Chang, Jie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Zhang, Lingyi [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan); Hu, Shijie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Huang, Hanlin, E-mail: huanghl@gdoh.org [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Ichihara, Gaku, E-mail: gak@rs.tus.ac.jp [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan)

    2015-01-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn{sup 2+})-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn{sup 2+}-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity. - Highlights: • 1-BP modified hippocampal phosphoproteome in rat and 23 altered proteins were identified. • 1-BP changed phosphorylation

  17. Developmental Toxic Effects of Exposure to Chemical Warfare Nerve Agents in Rats: Effects on Brain and Behavior

    Science.gov (United States)

    2015-03-01

    spatial memory, locomotor activity and vestibular motor function , as well as neuropathology. Similar to our adult model, we found that juvenile...rats exposed to GB exhibited deficits in vestibular motor function for up to 1 week and cognitive deficits in the Morris water maze at 3 weeks post...Preparation of rat brains for Golgi-Cox staining: Upon euthanasia, the brain of each animal was carefully removed from the skull. The cerebrum was blocked

  18. Targeting anandamide metabolism rescues core and associated autistic-like symptoms in rats prenatally exposed to valproic acid

    Science.gov (United States)

    Servadio, M; Melancia, F; Manduca, A; di Masi, A; Schiavi, S; Cartocci, V; Pallottini, V; Campolongo, P; Ascenzi, P; Trezza, V

    2016-01-01

    Autism spectrum disorders (ASD) are characterized by altered sociability, compromised communication and stereotyped/repetitive behaviors, for which no specific treatments are currently available. Prenatal exposure to valproic acid (VPA) is a known, although still underestimated, environmental risk factor for ASD. Altered endocannabinoid activity has been observed in autistic patients, and endocannabinoids are known to modulate behavioral traits that are typically affected in ASD. On this basis, we tested the hypothesis that changes in the endocannabinoid tone contribute to the altered phenotype induced by prenatal VPA exposure in rats, with focus on behavioral features that resemble the core and associated symptoms of ASD. In the course of development, VPA-exposed rats showed early deficits in social communication and discrimination, compromised sociability and social play behavior, stereotypies and increased anxiety, thus providing preclinical proof of the long-lasting deleterious effects induced by prenatal VPA exposure. At the neurochemical level, VPA-exposed rats displayed altered phosphorylation of CB1 cannabinoid receptors in different brain areas, associated with changes in anandamide metabolism from infancy to adulthood. Interestingly, enhancing anandamide signaling through inhibition of its degradation rescued the behavioral deficits displayed by VPA-exposed rats at infancy, adolescence and adulthood. This study therefore shows that abnormalities in anandamide activity may underlie the deleterious impact of environmental risk factors on ASD-relevant behaviors and that the endocannabinoid system may represent a therapeutic target for the core and associated symptoms displayed by autistic patients. PMID:27676443

  19. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane.

    Science.gov (United States)

    Huang, Zhenlie; Ichihara, Sahoko; Oikawa, Shinji; Chang, Jie; Zhang, Lingyi; Hu, Shijie; Huang, Hanlin; Ichihara, Gaku

    2015-01-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn(2+))-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p<0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn(2+)-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity.

  20. 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...

  1. 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.

  2. 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.

  3. Rat dams exposed repeatedly to a daily brief separation from the pups exhibit increased maternal behavior, decreased anxiety and altered levels of receptors for estrogens (ERα, ERβ), oxytocin and serotonin (5-HT1A) in their brain.

    Science.gov (United States)

    Stamatakis, Antonios; Kalpachidou, Theodora; Raftogianni, Androniki; Zografou, Efstratia; Tzanou, Athanasia; Pondiki, Stavroula; Stylianopoulou, Fotini

    2015-02-01

    In the present study we investigated the neurobiological mechanisms underlying expression of maternal behavior. Increased maternal behavior was experimentally induced by a brief 15-min separation between the mother and the pups during postnatal days 1 to 22. On postnatal days (PND) 12 and 22, we determined in experimental and control dams levels of anxiety in the elevated plus maze (EPM) as well as the levels of receptors for estrogens (ERα, ERβ), oxytocin (OTR) and serotonin (5-HT1AR) in areas of the limbic system (prefrontal cortex-PFC, hippocampus, lateral septum-SL, medial preoptic area-MPOA, shell of nucleus accumbens-nAc-Sh, central-CeA and basolateral-BLA amygdala), involved in the regulation of maternal behavior. Experimental dams, which showed increased maternal behavior towards their offspring, displayed reduced anxiety in the EPM on both PND12 and PND22. These behavioral differences could be attributed to neurochemical alterations in their brain: On both PND12 and PND22, experimental mothers had higher levels of ERα and OTRs in the PFC, hippocampus, CeA, SL, MPOA and nAc-Sh. The experimental manipulation-induced increase in ERβ levels was less widespread, being localized in PFC, the hippocampal CA2 area, MPOA and nAc-Sh. In addition, 5-HT1ARs were reduced in the PFC, hippocampus, CeA, MPOA and nAc-Sh of the experimental mothers. Our results show that the experience of the daily repeated brief separation from the pups results in increased brain ERs and OTRs, as well as decreased 5-HT1ARs in the dam's brain; these neurochemical changes could underlie the observed increase in maternal behavior and the reduction of anxiety.

  4. [The expression of GFAP after brain concussion in rats].

    Science.gov (United States)

    Zhang, Chun-Bing; Li, Yong-Hong

    2006-04-01

    To study the expression of GFAP and pathologic changes after rats brain concussion, so that to provide evidence on brain concussion for forensic identification. Forty-five SD rats were divided into 3, 6, 12, 24 h and 2, 4, 7, 10 d and normal control groups in terms of different wounding time after brain concussion model established, and the expression of GFAP after rats brain concussion were then observed by using SP immunohistochemical method. In normal control brain, low-level GFAP expressions could be observed. After six hours' brain concussion, GFAP positive cells increased obviously. The trend reached to the peak at 7d, partly declined at 10d, then decreased gradually. Brain concussion induced the expression of GFAP. The detection of GFAP could be useful for diagnosis of brain concussion on forensic pathology, and could be a reference index for timing of injury after brain concussion.

  5. 人参皂苷对慢性应激抑郁模型大鼠行为学及HPA轴、BDNF的影响%Effects of ginsenosides on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor in rats exposed to chronic unpredictable mild stress

    Institute of Scientific and Technical Information of China (English)

    刘丽琴; 罗艳; 张瑞睿; 郭建友

    2011-01-01

    Gingseng is commonly used in traditional Chinese medicine community for the treatment of depression-like dis, orders. Ginsenosides is considered to be the major active components of ginseng. Previous studies have demonstrated that ginsenosides produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to examine whether ginsenosides could affect the chronic unpredictable mild stress (CUMS)-induced depression in rats. The mechanism(s) underlying the antidepressant-like action was investigated by measuring serum corticesterone level, glucocorticoid receptor ( GR), mineralocorticoid receptor (MR) and brain-derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being lasted for 6 weeks, caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Whereas serum corticosterone level was significantly increased in rats exposed to CUMS, expressions of GR mRNA in hippocampus, and BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated rats. Daily intragastric administration of ginsenosides (12. 5, 25, 50 mg · kg-1) during the six weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. However, there was no significant difference in MR mRNA level among groups. The results suggest that the antidepressant-like action of ginsenosides is likely mediated by modulating the function of hypothalamic- pituitary -adrenal axis and increasing the expression of BDNF in brain tissues.%目的:探讨人参皂苷对慢性应激所致大鼠抑郁模型的干预作用.方法:通过测定大鼠血清中皮质酮(COR)、糖皮质激素受体(GR)、盐皮质激素受体(MR)和脑组织中神经营养(BDNF)的mRNA表达水平,探讨人参皂苷的抗抑郁机制.结果:与正常组大鼠比较,经过慢性应激6周后大鼠糖水偏好显著下降,强迫游泳测试不动时间

  6. Analysis of emotionality and locomotion in radio-frequency electromagnetic radiation exposed rats.

    Science.gov (United States)

    Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Paval, Jaijesh; Kedage, Vivekananda; Bhat, M Shankaranarayana; Nayak, Satheesha; Bhat, P Gopalakrishna

    2013-07-01

    In the current study the modulatory role of mobile phone radio-frequency electromagnetic radiation (RF-EMR) on emotionality and locomotion was evaluated in adolescent rats. Male albino Wistar rats (6-8 weeks old) were randomly assigned into the following groups having 12 animals in each group. Group I (Control): they remained in the home cage throughout the experimental period. Group II (Sham exposed): they were exposed to mobile phone in switch-off mode for 28 days, and Group III (RF-EMR exposed): they were exposed to RF-EMR (900 MHz) from an active GSM (Global system for mobile communications) mobile phone with a peak power density of 146.60 μW/cm(2) for 28 days. On 29th day, the animals were tested for emotionality and locomotion. Elevated plus maze (EPM) test revealed that, percentage of entries into the open arm, percentage of time spent on the open arm and distance travelled on the open arm were significantly reduced in the RF-EMR exposed rats. Rearing frequency and grooming frequency were also decreased in the RF-EMR exposed rats. Defecation boli count during the EPM test was more with the RF-EMR group. No statistically significant difference was found in total distance travelled, total arm entries, percentage of closed arm entries and parallelism index in the RF-EMR exposed rats compared to controls. Results indicate that mobile phone radiation could affect the emotionality of rats without affecting the general locomotion.

  7. 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.

  8. Effects of white spirits on rat brain 5-HT receptor functions and synaptic remodeling

    DEFF Research Database (Denmark)

    Lam, Henrik Rye; Plenge, P.; Jørgensen, O.S.

    2001-01-01

    Previously, inhalation exposure to different types of white spirit (i.e. complex mixtures of aliphatic, aromatic, alkyl aromatic, and naphthenic hydrocarbons) has been shown to induce neurochemical effects in rat brains. Especially, the serotonergic system was involved at the global, regional...... applied as indices for synaptic remodeling in forebrain, hippocampus, and entorhinal cortex. Male Wistar rats were exposed to 0, 400, or 800 ppm of aromatic (20 vol.% aromatic hydrocarbons) or dearomatized white spirit (catalytically hydrogenated white spirit) in the inhaled air for 6 h/day, 7 days...... that inhalation exposure to high concentrations of white spirit may be neurotoxic to rats, especially the aromatic white spirit type....

  9. Delayed extinction and stronger drug-primed reinstatement of methamphetamine seeking in rats prenatally exposed to morphine.

    Science.gov (United States)

    Shen, Ying-Ling; Chen, Shao-Tsu; Chan, Tzu-Yi; Hung, Tsai-Wei; Tao, Pao-Luh; Liao, Ruey-Ming; Chan, Ming-Huan; Chen, Hwei-Hsien

    2016-02-01

    Prenatal morphine (PM) affects the development of brain reward system and cognitive function. The present study aimed to determine whether PM exposure increases the vulnerability to MA addiction. Pregnant Sprague-Dawley rats were administered saline or morphine during embryonic days 3-20. The acquisition, extinction and reinstatement of methamphetamine (MA) conditioned place preference (CPP) and intravenous self-administration (SA) paradigms were assessed in the male adult offspring. There was no difference in the acquisition and expression of MA CPP between saline- and PM-exposed rats, whereas PM-exposed rats exhibited slower extinction and greater MA priming-induced reinstatement of drug-seeking behavior than controls. Similarly, MA SA under progressive ratio and fixed ratio schedules was not affected by PM exposure, but PM-exposed rats required more extinction sessions to reach the extinction criteria and displayed more severe MA priming-, but not cue-induced, reinstatement. Such alterations in extinction and reinstatement were not present when PM-exposed rats were tested in an equivalent paradigm assessing operant responding for food pellets. Our results demonstrate that PM exposure did not affect the association memory formation during acquisition of MA CPP or SA, but impaired extinction learning and increased MA-primed reinstatement in both tasks. These findings suggest that the offspring of women using morphine or heroin during pregnancy might predict persistent MA seeking during extinction and enhanced propensity to MA relapse although they might not be more susceptible to the reinforcing effect of MA during initiation of drug use.

  10. Extremely low frequency magnetic fields induce oxidative stress in rat brain.

    Science.gov (United States)

    Manikonda, Pavan K; Rajendra, Pilankatta; Devendranath, D; Gunasekaran, B; Channakeshava; Aradhya, Shivakumara R S; Sashidhar, Rao B; Subramanyam, Chivukula

    2014-01-01

    The present investigation was conducted to understand the influence of long-term exposure of rats to extremely low frequency magnetic fields (ELF-MF), focusing on oxidative stress (OS) on different regions of rat's brain. Male Wistar rats (21-day-old) were exposed to ELF-MF (50 Hz; 50 and 100 µT) for 90 days continuously; hippocampal, cerebellar and cortical regions from rats were analyzed for (i) reactive oxygen species (ROS), (ii) metabolites indicative of OS and (iii) antioxidant enzymes. In comparison to control group rats, the rats that were continuously exposed to ELF-MF caused OS and altered glutathione (GSH/GSSG) levels in dose-dependent manner in all the regions of the brain. Accumulation of ROS, lipid peroxidation end products and activity of superoxide dismutase in different regions was in the descending order of cerebellum glutathione peroxidase activity were in the descending order of hippocampus 50 µT. Varied influences observed in different regions of the brain, as documented in this study, may contribute to altered metabolic patterns in its related regions of the central nervous system, leading to aberrant neuronal functions.

  11. PROTECTIVE EFFECT OF LORANTHUS LONGIFLORUS ON LEARNING AND MEMORY OF RATS EXPOSED TO ELECTROMAGNETIC RADIATION (EMR

    Directory of Open Access Journals (Sweden)

    Hemant Nagar

    2013-06-01

    Full Text Available The interaction of mobile phone radio-frequency electromagnetic radiation (RF-EMR with the brain is a serious concern of our society. In this study, we aimed to experiment on the antioxidative property of a parasitic plant Loranthus longiflorus (Loranthaceae to protect central nervous system against oxidative damages of mobile phone electromagnetic radiation (EMR. Healthy male albino wistar rats were exposed to RF-EMR by giving 5 min calling/ 5min interval for 1 hour per day for two month, Keeping a GSM (0.9 GHz/1.8 GHz mobile phone in Silent mode (no ring tone in the cage. After 15, 30, 45, 60 days exposure, three randomly picked animals from both groups were tested with using Morris water maze. Antioxidant compounds and their Neuroprotective action of Loranthus longiflorus bark sample collected from Ficus religiosa host trees were assessed. Rats which have been feed with Ethyl acetate Extract of Loranthus longiflorus (EAL bark (700mg/kg body weight, p.o.

  12. Metabonomic study of rats exposed to cigarette sidestream smoke

    Institute of Scientific and Technical Information of China (English)

    LIAN Wen-liu; SHI Xian-zhe; LUO Jia; REN Feng-lian

    2016-01-01

    A metabonomic approach was undertaken in order to detect urinary endogenous and exogenous metabolites and to evaluate the effects of passive exposure to cigarette sidestream smoke on rats. Urinary samples from three groups of rats were determined including control rats, rats treated with blended cigarettes (nonmenthol cigarettes) and rats treated with menthol cigarettes. The total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), total 1-hydroxypyrene (1-HOP) and 3-hydroxybenzo[a] pyrene (3-HOBaP) were determined for assessing exposure to cigarette sidestream smoke toxins. Urinary endogenous metabolites in the three groups of rats were also analyzed and the data were processed by chemometrics. Eleven endogenous metabolites were found and identified. Their relative levels were compared among the three groups. The results show that cigarette sidestream smoke has complex effect on rats. Blended cigarette group makes difference to menthol cigarette group in the rats' urinary metabolic changes. Menthol adding to cigarettes has positive and negative effects on rats, respectively. The urinary metabolic profiling of menthol cigarette group is closer to that of control group.

  13. Localized delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat brain using focused ultrasound.

    Science.gov (United States)

    Mulik, Rohit S; Bing, Chenchen; Ladouceur-Wodzak, Michelle; Munaweera, Imalka; Chopra, Rajiv; Corbin, Ian R

    2016-03-01

    Focused ultrasound exposures in the presence of microbubbles can achieve transient, non-invasive, and localized blood-brain barrier (BBB) opening, offering a method for targeted delivery of therapeutic agents into the brain. Low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) could have significant therapeutic value in the brain, since DHA is known to be neuroprotective. BBB opening was achieved using pulsed ultrasound exposures in a localized brain region in normal rats, after which LDL nanoparticles containing the fluorescent probe DiR (1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindotricarbocyanine Iodide) or DHA were administered intravenously. Fluorescent imaging of brain tissue from rats administered LDL-DiR demonstrated strong localization of fluorescence signal in the exposed hemisphere. LDL-DHA administration produced 2 × more DHA in the exposed region of the brain, with a corresponding increase in Resolvin D1 levels, indicating DHA was incorporated into cells and metabolized. Histological evaluation did not indicate any evidence of increased tissue damage in exposed brain regions compared to normal brain. This work demonstrates that localized delivery of DHA to the brain is possible using systemically-administered LDL nanoparticles combined with pulsed focused ultrasound exposures in the brain. This technology could be used in regions of acute brain injury or as a means to target infiltrating tumor cells in the brain.

  14. Effect of manganese on the concentration of amino acids in different regions of the rat brain.

    Science.gov (United States)

    Lipe, G W; Duhart, H; Newport, G D; Slikker, W; Ali, S F

    1999-01-01

    The present study was designed to determine if chronic exposure of weanlings and adult rats to Mn produces significant alterations in amino acid concentrations in different regions of the rat brain. Weanling (30 day old) and adult (90 day old) male rats were exposed to 10 and 20 mg Mn/kg body weight per day, by gavage, for 30 days. Forty-eight hours after the last dose, animals were sacrificed by decapitation and brains were dissected into different regions to determine the concentration of amino acids by HPLC/EC. A dose dependent decrease in body weight gain was found in the adult, but not in the weanling rats. Significant increases occurred in concentrations of aspartate, glutamate, glutamine, taurine and gamma-aminobutyric acid (GABA) in the cerebellum of the adult rats dosed with 20 mg/kg per day, Mn. A significant decrease in the concentration of glutamine was observed in caudate nucleus and hippocampus of weanling rats dosed with 10 mg/kg, Mn. These data suggest that chronic Mn exposure can produce a decrease in body weight gain in adult rats and alterations in amino acids in different regions of weanling and adult rat brains.

  15. Effect of kombucha on some trace element levels in different organs of electromagnetic field exposed rats

    Directory of Open Access Journals (Sweden)

    Ola A. Gharib

    2014-01-01

    Full Text Available Mobile phones have increased exponentially all over the world. The present study was performed to evaluate the effect of kombucha (KT on some trace element levels of brain, spleen and intestine in male albino rats exposed to a 950 MHz electromagnetic field (EMF. Four experimental groups labelled as controls, EMF group, KT group and KT + EMF group were formed with six randomly chosen animals in each group. After EMF exposure for eight weeks and the animals were sacrificed by decapitation. Brain, spleen and intestine samples were collected for trace element analysis. The group of animals subjected to electromagnetic waves caused significant increases in iron copper levels and copper/zinc ratio accompanied with a decrease of zinc level in all studied organs. Combined treatment of kombucha with EMF resulted in a successful attenuation of these adverse effects of EMF. From present findings we can state that kombucha as a supplement has an ameliorative signs against the effects of electromagnetic radiation.

  16. Dendropanax morbifera Léveille extract facilitates cadmium excretion and prevents oxidative damage in the hippocampus by increasing antioxidant levels in cadmium-exposed rats

    OpenAIRE

    2014-01-01

    Background Dendropanax morbifera Léveille is used in herbal medicine as a cancer treatment. In this study, we investigated the effects of Dendropanax morbifera stem extract (DMS) on cadmium (Cd) excretion from the blood and kidney and brain tissues of rats exposed to cadmium, as well as the effects of DMS on oxidative stress and antioxidant levels in the hippocampus after Cd exposure. Methods Seven-week-old Sprague-Dawley rats were exposed to 2 mg/kg of cadmium by intragastric gavage and were...

  17. Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures

    Directory of Open Access Journals (Sweden)

    Adelisandra S. S. Castelhano

    2013-05-01

    Full Text Available Neonatal seizures are the most common manifestation of neurological dysfunction in the neonate. The prognosis of neonatal seizures is highly variable, and the controversy remains whether the severity, duration or frequency of seizures may contribute to brain damage independently of its etiology. Animal data indicates that seizures during development are associated with a high probability of long-term adverse effects such as learning and memory impairment, behavioral changes and even epilepsy, which is strongly age dependent, as well as the severity, duration and frequency of seizures. In preliminary studies, we demonstrated that adolescent male rats exposed to one-single neonatal status epilepticus (SE episode showed social behavior impairment, and we proposed the model as relevant for studies of developmental disorders. Based on these facts, the goal of this study was to verify the existence of a persistent deficit and if the anxiety-related behavior could be associated with that impairment. To do so, male Wistar rats at 9 days postnatal were submitted to a single episode of status epilepticus (SE by pilocarpine injection (380 mg/kg, i.p. and control animals received saline (0.9 %, 0,1mL/10 g. It was possible to demonstrate that in adulthood, animals exposed to neonatal SE displayed low preference for social novelty, anxiety-related behavior and increased stereotyped behavior in anxiogenic environment with no locomotor activity changes. On the balance, these data suggests that neonatal status epilepticus in rodents leads to altered anxiety-related and abnormal social behaviors.

  18. Developmental immunotoxicity of Diazepam in prenatally exposed weanling Wistar rats

    NARCIS (Netherlands)

    Loveren H van; Piersma AH; Jong WH de; Waal EJ de; LPI; LEO; LGM

    1999-01-01

    A prenatal developmental toxicity study was conducted in rats receiving the pharmaceutical Diazepam from gestation days 14 to 20. Reports from the literature claim that Diazepam has impaired the immune function in the offspring of rats receiving treatment during the third trimester of gestation. Dia

  19. Changes of brain-derived neurotrophic factor in hippocampus of chronic lead-exposed rats%慢性染铅大鼠海马脑源性神经营养因子的改变

    Institute of Scientific and Technical Information of China (English)

    刘亚华; 李积胜; 杨烽; 王大宁; 曹广军

    2003-01-01

    目的探讨慢性染铅大鼠海马脑源性神经营养因子(Brain derived neurotrophic factor,BDNF)的变化.方法Wistar大鼠分别饮用0.02%、0.2%的醋酸铅(PbAc)溶液,染铅3个月后,通过Y-迷宫实验检测各组动物学习记忆行为变化,采用免疫组织化学ABC法观察各组大鼠海马CA1区、CA3区和齿状回BDNF阳性神经元数目的改变.结果在正常情况下,BDNF样免疫阳性神经元在海马各区及齿状回均有分布.与对照组相比,饮用0.02%和0.2%PbAc两组染铅大鼠学习记忆能力明显降低(P<0.05),同时两组染铅大鼠海马CA1区、CA3区和齿状回的BDNF阳性神经元数均明显减少(P<0.05).结论海马各区BDNF阳性神经元数目的减少可能是大鼠染铅后学习记忆功能受损的机制之一.

  20. 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.

  1. The effects of in vitro exposure to white spirit on [Ca2+] in synaptosomes from rats exposed prenatally to white spirit

    DEFF Research Database (Denmark)

    Edelfors, S.; Hass, Ulla; Ravn-Jonsen, A.

    1999-01-01

    in all groups of rats. The membrane leakage measured as FURA-2 leakage from the synaptosomes identical in all three groups of animals. The results suggest that prenatal exposure to white spirit induces long-lasting and possibly irreversible changes in calcium homeostasis in the rat nervous system.......Female rats were exposed to white spirit (400 and 800 ppm for 6 hr/day) at day 7-20 during pregnancy. Thirty-five days after birth all female offspring were sacrificed, the brains removed, and the synaptosomal fractions prepared for in vitro studies. The cytosolic calcium concentration was measured...

  2. Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields

    Science.gov (United States)

    Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela

    2016-06-01

    An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform’s size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke’s brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.

  3. The influence of microwave radiation from cellular phone on fetal rat brain.

    Science.gov (United States)

    Jing, Ji; Yuhua, Zhang; Xiao-qian, Yang; Rongping, Jiang; Dong-mei, Guo; Xi, Cui

    2012-03-01

    The increasing use of cellular phones in our society has brought focus on the potential detrimental effects to human health by microwave radiation. The aim of our study was to evaluate the intensity of oxidative stress and the level of neurotransmitters in the brains of fetal rats chronically exposed to cellular phones. The experiment was performed on pregnant rats exposed to different intensities of microwave radiation from cellular phones. Thirty-two pregnant rats were randomly divided into four groups: CG, GL, GM, and GH. CG accepted no microwave radiation, GL group radiated 10 min each time, GM group radiated 30 min, and GH group radiated 60 min. The 3 experimental groups were radiated 3 times a day from the first pregnant day for consecutively 20 days, and on the 21st day, the fetal rats were taken and then the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), noradrenaline (NE), dopamine (DA), and 5-hydroxyindole acetic acid (5-HT) in the brain were assayed. Compared with CG, there were significant differences (Pcellular phones during pregnancy has certain harm on fetal rat brains.

  4. Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats.

    Science.gov (United States)

    Thompson, Murray R; Callaghan, Paul D; Hunt, Glenn E; McGregor, Iain S

    2008-05-15

    The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 x 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT(1A) agonist 8-OH-DPAT (250 microg/kg but not 125 microg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT(1A) receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA.

  5. Forced exercise improves passive avoidance memory in morphine-exposed rats.

    Science.gov (United States)

    Saadipour, K; Sarkaki, A; Alaei, H; Badavi, M; Rahim, F

    2009-09-01

    The aim of this study was to investigate the effect of short-term forced exercise protocol on passive avoidance retention in morphine-exposed rats. Effects of morphine on acquisition and retrieval of retention have been proven in the avoidance paradigms. Twenty four male Wistar rats weighing 250-300 g were used in this study. Animals were randomly divided into four groups including: (1) non-morphine-exposed without exercise (nA.nE) (2) non-morphine-exposed with exercise (nA.E) (3) morphine-exposed without exercise (A.nE) and (4) morphine-exposed with exercise (A.E). Rats ran as forced exercise on the motorized treadmill 1 h daily for ten days. Morphine-exposed animals received intraperitoneal morphine during first 5 days of the exercise period and their dependence to morphine was confirmed by naloxane admistration (10 mg kg(-1), i.p.) and withdrawal test. After 10 days of forced exercise, step down latency was tested and Inflexion Ratio (IR) was evaluated in each rat. Baseline step down latencies before any morphine exposing or exercise have shown no significant alteration in all groups. Inflexion Ratio (IR) ofnA.E group has increased significantly (pexercise on treadmill improved retention in both morphine-exposed and non morphine-exposed rats at least up to 7 days and more than 14 days, respectively. Alteration in retention between exercised groups may attribute the release of adrenal stress hormones such as epinephrine and corticosterone because of the emotional arousal.

  6. Development of sensory motor reflexes in 2 G exposed rats.

    Science.gov (United States)

    Wubbels, Réne; Bouët, Valentine; de Jong, Herman; Gramsbergen, Albert

    2004-07-01

    During gestation and early postnatal development, the animal's size and weight rapidly increase. Within that period, gravity affects sensory and motor development. We studied age-dependent modifications of several types of motor reflexes in 5 groups of rats conceived, born and reared in hypergravity (HG; 2 g). These rats were transferred to normal gravity (NG; 1 g) at various postnatal days, and their behavioral reflexes were compared with a control group which was constantly kept under NG. HG induced a retarded development of vestibular dependent reflexes. Other types of motor behavior were not delayed.

  7. Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

    Science.gov (United States)

    Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

    2017-02-01

    Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

  8. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Yazir, Yusufhan; Utkan, Tijen; Gacar, Nejat; Aricioglu, Feyza

    2015-01-01

    A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation.

  9. Recruitment of hypothalamic orexin neurons after formalin injections in adult male rats exposed to a neonatal immune challenge

    Directory of Open Access Journals (Sweden)

    Erin Jane Campbell

    2015-03-01

    Full Text Available Exposure to early life physiological stressors, such as infection, is thought to contribute to the onset of psychopathology in adulthood. In animal models, injections of the bacterial immune challenge, lipopolysaccharide (LPS, during the neonatal period has been shown to alter both neuroendocrine function and behavioural pain responses in adulthood. Interestingly, recent evidence suggests a role for the lateral hypothalamic peptide orexin in stress and nociceptive processing. However, whether neonatal LPS exposure affects the reactivity of the orexin system to formalin-induced inflammatory pain in later life remains to be determined. Male Wistar rats (n=13 were exposed to either LPS or saline (0.05mg/kg, i.p on postnatal days (PND 3 and 5. On PND 80-97, all rats were exposed to a subcutaneous hindpaw injection of 2.25% formalin. Following behavioural testing, animals were perfused and brains processed for Fos-protein and orexin immunohistochemistry. Rats treated with LPS during the neonatal period exhibited decreased licking behaviours during the interphase of the formalin test, the period typically associated with the active inhibition of pain, and increased grooming responses to formalin in adulthood. Interestingly, these behavioural changes were accompanied by an increase in the percentage of Fos-positive orexin cells in the dorsomedial and perifornical hypothalamus in LPS-exposed animals. Similar increases in Fos-protein were also observed in stress and pain sensitive brain regions that receive orexinergic inputs. These findings highlight a potential role for orexin in the behavioural responses to pain and provide further evidence that early life stress can prime the circuitry responsible for these responses in adulthood.

  10. Multiple endocrine disrupting effects in rats perinatally exposed to butylparaben

    DEFF Research Database (Denmark)

    Boberg, Julie; Petersen, Marta Axelstad; Svingen, Terje

    2016-01-01

    Parabens comprise a group of preservatives commonly added to cosmetics, lotions and other consumer products. Butylparaben has estrogenic and anti-androgenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine...

  11. Multiple endocrine disrupting effects in rats perinatally exposed to butylparaben

    DEFF Research Database (Denmark)

    Boberg, Julie; Petersen, Marta Axelstad; Svingen, Terje

    2016-01-01

    Parabens comprise a group of preservatives commonly added to cosmetics, lotions and other consumer products. Butylparaben has estrogenic and anti-androgenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine...

  12. Regional energy balance in rat brain after transient forebrain ischemia.

    Science.gov (United States)

    Pulsinelli, W A; Duffy, T E

    1983-05-01

    Phosphocreatine, ATP, and glucose were severely depleted, and the lactate levels were increased in the paramedian neocortex, dorsal-lateral striatum, and CA1 zone of hippocampus of rats exposed to 30 min of forebrain ischemia. Upon recirculation of the brain, phosphocreatine, ATP, and lactate concentrations recovered to control values in the paramedian neocortex and CA1 zone of hippocampus and to near-control values in the striatum. The phosphocreatine and ATP concentrations then fell and the lactate levels rose in the striatum after 6-24 h, and in the CA1 zone of hippocampus after 24-72 h. The initial recovery and subsequent delayed changes in the phosphocreatine, ATP, and lactate concentrations in the striatum and hippocampus coincided with the onset and progression of morphological injury in these brain regions. The results suggest that cells in these regions regain normal or near-normal mitochondrial function and are viable, in terms of energy production, for many hours before unknown mechanisms cause irreversible neuronal before unknown mechanisms cause irreversible neuronal injury.

  13. 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.

  14. 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

  15. Pax6-dependent cortical glutamatergic neuronal differentiation regulates autism-like behavior in prenatally valproic acid-exposed rat offspring.

    Science.gov (United States)

    Kim, Ki Chan; Lee, Dong-Keun; Go, Hyo Sang; Kim, Pitna; Choi, Chang Soon; Kim, Ji-Woon; Jeon, Se Jin; Song, Mi-Ryoung; Shin, Chan Young

    2014-02-01

    Imbalance in excitatory/inhibitory signal in the brain has been proposed as one of the main pathological features in autism spectrum disorders, although the underlying cellular and molecular mechanism is unclear yet. Because excitatory/inhibitory imbalance can be induced by aberration in glutamatergic/GABAergic neuronal differentiation, we investigated the mechanism of dysregulated neuronal differentiation between excitatory and inhibitory neurons in the embryonic and postnatal brain of prenatally valproic acid-exposed rat offspring, which is often used as an animal model of autism spectrum disorders. Transcription factor Pax6, implicated in glutamatergic neuronal differentiation, was transiently increased in embryonic cortex by valproate exposure, which resulted in the increased expression of glutamatergic proteins in postnatal brain of offspring. Chromatin immunoprecipitation showed increased acetylated histone binding on Pax6 promoter region, which may underlie the transcriptional up-regulation of Pax6. Other histone deacetylase (HDAC) inhibitors including TSA and SB but not valpromide, which is devoid of HDAC inhibitor activity, induced Pax6 up-regulation. Silencing Pax6 expression in cultured rat primary neural progenitor cells demonstrated that up-regulation of Pax6 plays an essential role in valproate-induced glutamatergic differentiation. Blocking glutamatergic transmission with MK-801 or memantine treatment, and to a lesser extent with MPEP treatment, reversed the impaired social behaviors and seizure susceptibility of prenatally valproate-exposed offspring. Together, environmental factors may contribute to the imbalance in excitatory/inhibitory neuronal activity in autistic brain by altering expression of transcription factors governing glutamatergic/GABAergic differentiation during fetal neural development, in conjunction with the genetic preload.

  16. Effects of Nonylphenol on Brain Gene Expression Profiles in F1 Generation Rats

    Institute of Scientific and Technical Information of China (English)

    YIN-YIN XIA; PING ZHANG; YANG WANG

    2008-01-01

    Objective To explore the effects of nonylphenol on brain gene expression profiles in F1 generation rats by microarray technique.Methods mRNA was extracted from the brain of 2-day old F1 generation male rats Whose F0 female generation was either exposed to nonylphenol or free from nonylphenol exposure,and then it was reversely transcribed to cDNA hbeled with cy5 and cy3 fluorescence.Subsequently,cDNA probes were hybridized to two BiostarR-40S cDNA gene chips and fluorescent signals of cy5 and cy3 were scanned and analyzed. Results Two genes were differentially down-regulated.Conclusion Nonylphenol may disturb the neurcendocrine function of male rats when administered perinatally.

  17. Hippocampal-dependent Pavlovian conditioning in adult rats exposed to binge-like doses of ethanol as neonates.

    Science.gov (United States)

    Lindquist, Derick H

    2013-04-01

    Binge-like postnatal ethanol exposure produces significant damage throughout the brain in rats, including the cerebellum and hippocampus. In the current study, cue- and context-mediated Pavlovian conditioning were assessed in adult rats exposed to moderately low (3E; 3g/kg/day) or high (5E; 5g/kg/day) doses of ethanol across postnatal days 4-9. Ethanol-exposed and control groups were presented with 8 sessions of trace eyeblink conditioning followed by another 8 sessions of delay eyeblink conditioning, with an altered context presented over the last two sessions. Both forms of conditioning rely on the brainstem and cerebellum, while the more difficult trace conditioning also requires the hippocampus. The hippocampus is also needed to gate or modulate expression of the eyeblink conditioned response (CR) based on contextual cues. Results indicate that the ethanol-exposed rats were not significantly impaired in trace EBC relative to control subjects. In terms of CR topography, peak amplitude was significantly reduced by both doses of alcohol, whereas onset latency but not peak latency was significantly lengthened in the 5E rats across the latter half of delay EBC in the original training context. Neither dosage resulted in significant impairment in the contextual gating of the behavioral response, as revealed by similar decreases in CR production across all four treatment groups following introduction of the novel context. Results suggest ethanol-induced brainstem-cerebellar damage can account for the present results, independent of the putative disruption in hippocampal development and function proposed to occur following postnatal ethanol exposure.

  18. Micronucleated Erythrocytes in Newborn Rats Exposed to Raltegravir Placental Transfer

    Science.gov (United States)

    Torres-Mendoza, Blanca Miriam; Coronado-Medina, Damharis Elizabeth; Vázquez-Valls, Eduardo; Zamora-Perez, Ana Lourdes; Lemus-Varela, María de Lourdes

    2014-01-01

    The use of raltegravir in treating HIV/AIDS has been proposed due to its effectiveness in suppressing high loads of HIV RNA in pregnant women, thus preventing infection of the fetus. However, administration of raltegravir during pregnancy produces a compound which is transferred to high concentrations to the offspring. The objective of this study is to evaluate the transplacental genotoxic effect of raltegravir in newborn rats. We evaluated the number of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE), and polychromatic erythrocytes (PCE) in the peripheral blood samples of the offspring of Wistar rats treated 6 days before birth with oral administration of raltegravir. The animals were randomly assigned to five groups as follows: raltegravir at doses of 15, 30, or 60 mg/day, cyclophosphamide 10 mg/kg (positive control), or 0.5 ml of sterile water (negative control). In addition, the effect of these drugs on the weight and height of newborns was assessed. There were no differences in the number of MNE, MNPCE, and PCE, and a slight decrease in the weight and height was observed in the offspring of the rat mothers treated with raltegravir. Genotoxicity studies are required in pregnant women to determine the risk of using raltegravir to the fetuses. PMID:24977162

  19. Micronucleated Erythrocytes in Newborn Rats Exposed to Raltegravir Placental Transfer

    Directory of Open Access Journals (Sweden)

    Blanca Miriam Torres-Mendoza

    2014-01-01

    Full Text Available The use of raltegravir in treating HIV/AIDS has been proposed due to its effectiveness in suppressing high loads of HIV RNA in pregnant women, thus preventing infection of the fetus. However, administration of raltegravir during pregnancy produces a compound which is transferred to high concentrations to the offspring. The objective of this study is to evaluate the transplacental genotoxic effect of raltegravir in newborn rats. We evaluated the number of micronucleated erythrocytes (MNE, micronucleated polychromatic erythrocytes (MNPCE, and polychromatic erythrocytes (PCE in the peripheral blood samples of the offspring of Wistar rats treated 6 days before birth with oral administration of raltegravir. The animals were randomly assigned to five groups as follows: raltegravir at doses of 15, 30, or 60 mg/day, cyclophosphamide 10 mg/kg (positive control, or 0.5 ml of sterile water (negative control. In addition, the effect of these drugs on the weight and height of newborns was assessed. There were no differences in the number of MNE, MNPCE, and PCE, and a slight decrease in the weight and height was observed in the offspring of the rat mothers treated with raltegravir. Genotoxicity studies are required in pregnant women to determine the risk of using raltegravir to the fetuses.

  20. Clinical course of brain stroke in the persons exposed to ionizing radiation under the production conditions

    Energy Technology Data Exchange (ETDEWEB)

    Bouchmanov, A. [State Research Center of Russia, Moscow (Russian Federation). Inst. of Biophysics

    2000-05-01

    The purpose was to study the risk factors and clinical course of brain strokes in professionally exposed workers being employed in plutonium production in comparison with a control group. The method and materials of study -clinical supervision and clinical database creation on 162 cases of brain stroke (128 males and 34 females) developed among professionally exposed workers. Age of patient varied from 21 to 68 years (in average -51.6 y.). The control group consisted of patients with the same diagnosis, worked on the same enterprise, but non-exposed to radiation. Data on the totally accumulated dose of external gamma radiation were received on the base of the individual dosimeters (from 0.1 cSv to 52 cSv, in average about 13 cSv); the plutonium-239 body content was estimated accordingly to the level of urine radionuclide excretion (from 0.4 kBq to 1.6 kBq, in average about 0.33 kBq). Muscle's hypertinsion and pathological great-toe reflexes in paretic legs and hands, hemianopsia, impressive and ataxic aphasia prevailed in the patients with ischemic brain strokes in system of internal carotid artery, exposed to radiation. The changes of muscle's tension, ataxia and nystagmus were marked more often in the professionals with ischemic brain strokes in system of vertebrobasilar artery. The illness proceeded more easy and with smaller frequency of frustration of consciousness and algesthesia, irrespective of a type ischemic brain strokes in the people exposed to ionizing radiation, than in patients of non-irradiated group. It was found that the arterial hypertension appeared to be the main risk factor for the brain stroke in both groups of patients (in 81.48% and 91.15% of cases). There was no marked differences in significance of risk factors and in main clinical parameters of various types of ischemic brain strokes among the patients professionally exposed to radiation in comparison with a control group. (author)

  1. 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.

  2. Oxidative stress and superoxide dismutase activity in brain of rats ...

    African Journals Online (AJOL)

    JTEkanem

    effect of superoxide dismutase (SOD) activity in brain homogenates of Wistar rats. Oxidative stress measured as ... SOD is an important enzyme family in living cells for maintaining ..... one unit of activity with oxidation rate of organic substrate in.

  3. Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress.

    Science.gov (United States)

    Gray, Jason D; Punsoni, Michael; Tabori, Nora E; Melton, Jay T; Fanslow, Victoria; Ward, Mary J; Zupan, Bojana; Menzer, David; Rice, Jackson; Drake, Carrie T; Romeo, Russell D; Brake, Wayne G; Torres-Reveron, Annelyn; Milner, Teresa A

    2007-07-04

    Thousands of children receive methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), yet the long-term neurochemical consequences of MPH treatment are unknown. To mimic clinical Ritalin treatment in children, male rats were injected with MPH (5 mg/kg) or vehicle twice daily from postnatal day 7 (PND7)-PND35. At the end of administration (PND35) or in adulthood (PND135), brain sections from littermate pairs were immunocytochemically labeled for neurotransmitters and cytological markers in 16 regions implicated in MPH effects and/or ADHD etiology. At PND35, the medial prefrontal cortex (mPFC) of rats given MPH showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase (TH), 60% more Nissl-stained cells, and 40% less norepinephrine transporter (NET)-ir density. In hippocampal dentate gyrus, MPH-receiving rats showed a 51% decrease in NET-ir density and a 61% expanded distribution of the new-cell marker PSA-NCAM (polysialylated form of neural cell adhesion molecule). In medial striatum, TH-ir decreased by 21%, and in hypothalamus neuropeptide Y-ir increased by 10% in MPH-exposed rats. At PND135, MPH-exposed rats exhibited decreased anxiety in the elevated plus-maze and a trend for decreased TH-ir in the mPFC. Neither PND35 nor PND135 rats showed major structural differences with MPH exposure. These findings suggest that developmental exposure to high therapeutic doses of MPH has short-term effects on select neurotransmitters in brain regions involved in motivated behaviors, cognition, appetite, and stress. Although the observed neuroanatomical changes largely resolve with time, chronic modulation of young brains with MPH may exert effects on brain neurochemistry that modify some behaviors even in adulthood.

  4. Neuroplasticity Changes of Rat Brain by Musical Stimuli during Fetal Period

    Directory of Open Access Journals (Sweden)

    Siamak Sheikhi

    2015-01-01

    Full Text Available Objective: Fetal development of the central nervous system is an important and sensitive stage which is affected by many external and internal stimuli. This study aimed to investigate effect of musical stimuli on fetal rat brain. Materials and Methods: In this experimental study, twelve female Wistar rats were selected and evenly assigned to control and musical groups. The females were mated with a male rat of the same genotype. Musical group was exposed to classic music with 60 dB power for 90 minutes twice per day from 2nd to 20th day of gestation. The control rats were handled similar to the musical group, but were not exposed to music. Before parturition, all the dams were anesthetized, and their blood samples were obtained and used for corticosterone (COS measurement. They were transcardially perfused by electron microscope (EM fixative agent. The fetal brains were extracted intact and used for slice preparation. Horizontal slices were made for electron microscope preparation, and images were taken and analyzed in terms of cell density and morphological changes. Results: EM observation indicated significant morphological difference in cellular and intercellular spaces between the two groups. Music-treated fetuses had significantly higher cell density in parietal cortex and music-treated dams had lower COS level. Conclusion: It was concluded that prenatal music would have a great impact on neuroplasticity of fetal rat brain, at least indirectly. Although the rat fetuses cannot hear until birth, music-induced reduction in COS blood level of dams might be the reason for neuroplasticity of fetal brain.

  5. Late reproductive analysis in rat male offspring exposed to nicotine during pregnancy and lactation.

    Science.gov (United States)

    Miranda-Spooner, M; Paccola, C C; Neves, F M O; de Oliva, S U; Miraglia, S M

    2016-03-01

    We previously observed that nicotine, administered to rats (Wistar) during pregnancy and lactation periods, provokes, in the progeny, late morphofunctional alterations in Leydig cell, body weight increase in adulthood (90 days post partum, dpp) as well as seminiferous epithelium injury. Aiming to investigate whether the spermatogenic damage previously observed in adult progenies from pregnant and lactating nicotine-exposed rat dams are maintained or whether it is worsened in older rats, we analyzed the morphological testicular alterations after up to two complete periods of spermatogenesis (53 days each), spermatic parameters, and sperm DNA fragmentation. Pregnant and lactating rats were nicotine-exposed (2 mg/kg/day) through an osmotic minipump implanted on the first day of pregnancy and replaced after birth. Absolute Control (no minipump) and Sham Control (minipump without nicotine) groups were established. The offspring were killed at 90, 143, and 196 dpp. Significant alterations in morphometric and stereological testicular parameters, such as concentration of sperm number, daily sperm production, and plasma and intratesticular levels of cholesterol and testosterone were not observed in nicotine-exposed rats. Testicular histopathological analysis showed small intraepithelial vacuolization and an accentuated germ cell desquamation in exposed rats. However, the offspring from nicotine-exposed dams exhibited higher frequency of morphologically abnormal spermatozoa and lower sperm motility in comparison with control groups. In addition, nicotine-exposed groups showed a significant reduction in sperm mitochondrial activity and an increased sperm DNA fragmentation (Comet assay). These results indicate a late reproductive damage in the male progeny caused by maternal nicotine exposure, related to the decrease in sperm quality.

  6. Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation.

    Science.gov (United States)

    Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Karun, Kalesh M; Nayak, Satheesha B; Bhat, P Gopalakrishna

    2015-10-01

    The effects of chronic and repeated radiofrequency electromagnetic radiation (RFEMR) exposure on spatial cognition and hippocampal architecture were investigated in prepubescent rats. Four weeks old male Wistar rats were exposed to RF-EMR (900 MHz; SAR-1.15 W/kg with peak power density of 146.60 μW/cm(2)) for 1 h/day, for 28 days. Followed by this, spatial cognition was evaluated by Morris water maze test. To evaluate the hippocampal morphology; H&E staining, cresyl violet staining, and Golgi-Cox staining were performed on hippocampal sections. CA3 pyramidal neuron morphology and surviving neuron count (in CA3 region) were studied using H&E and cresyl violet stained sections. Dendritic arborization pattern of CA3 pyramidal neuron was investigated by concentric circle method. Progressive learning abilities were found to be decreased in RF-EMR exposed rats. Memory retention test performed 24 h after the last training revealed minor spatial memory deficit in RF-EMR exposed group. However, RF-EMR exposed rats exhibited poor spatial memory retention when tested 48 h after the final trial. Hirano bodies and Granulovacuolar bodies were absent in the CA3 pyramidal neurons of different groups studied. Nevertheless, RF-EMR exposure affected the viable cell count in dorsal hippocampal CA3 region. RF-EMR exposure influenced dendritic arborization pattern of both apical and basal dendritic trees in RF-EMR exposed rats. Structural changes found in the hippocampus of RF-EMR exposed rats could be one of the possible reasons for altered cognition.

  7. Effects of fluoxetine on protein expression of potassium ion channels in the brain of chronic mild stress rats

    OpenAIRE

    Chunlin Chen; Ling Wang; Xianfang Rong; Weiping Wang; Xiaoliang Wang

    2015-01-01

    The purpose of this study is to investigate the expression of major potassium channel subtypes in the brain of chronical mild stress (CMS) rats and reveal the effects of fluoxetine on the expression of these channels. Rats were exposed to a variety of unpredictable stress for three weeks and induced anhedonia, lower sucrose preference, locomotor activity and lower body weight. The protein expressions were determined by Western blot. CMS significantly increased the expression of Kv2.1 channel ...

  8. Cardioprotective effect of cannabidiol in rats exposed to doxorubicin toxicity.

    Science.gov (United States)

    Fouad, Amr A; Albuali, Waleed H; Al-Mulhim, Abdulruhman S; Jresat, Iyad

    2013-09-01

    The potential protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against doxorubicin cardiotoxicity in rats. Cardiotoxicity was induced by six equal doses of doxorubicin (2.5mgkg(-1) i.p., each) given at 48h intervals over two weeks to achieve a total dose of 15mgkg(-1). Cannabidiol treatment (5mgkg(-1)/day, i.p.) was started on the same day of doxorubicin administration and continued for four weeks. Cannabidiol significantly reduced the elevations of serum creatine kinase-MB and troponin T, and cardiac malondialdehyde, tumor necrosis factor-α, nitric oxide and calcium ion levels, and attenuated the decreases in cardiac reduced glutathione, selenium and zinc ions. Histopathological examination showed that cannabidiol ameliorated doxorubicin-induced cardiac injury. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in cardiac tissue of doxorubicin-treated rats. These results indicate that cannabidiol represents a potential protective agent against doxorubicin cardiac injury.

  9. Voluntary Alcohol Intake following Blast Exposure in a Rat Model of Mild Traumatic Brain Injury

    Science.gov (United States)

    Lim, Yi Wei; Meyer, Nathan P.; Shah, Alok S.; Budde, Matthew D.; Stemper, Brian D.; Olsen, Christopher M.

    2015-01-01

    Alcoholism is a frequent comorbidity following mild traumatic brain injury (mTBI), even in patients without a previous history of alcohol dependence. Despite this correlational relationship, the extent to which the neurological effects of mTBI contribute to the development of alcoholism is unknown. In this study, we used a rodent blast exposure model to investigate the relationship between mTBI and voluntary alcohol drinking in alcohol naïve rats. We have previously demonstrated in Sprague Dawley rats that blast exposure leads to microstructural abnormalities in the medial prefrontal cortex (mPFC) and other brain regions that progress from four to thirty days. The mPFC is a brain region implicated in alcoholism and drug addiction, although the impact of mTBI on drug reward and addiction using controlled models remains largely unexplored. Alcohol naïve Sprague Dawley rats were subjected to a blast model of mTBI (or sham conditions) and then tested in several common measures of voluntary alcohol intake. In a seven-week intermittent two-bottle choice alcohol drinking test, sham and blast exposed rats had comparable levels of alcohol intake. In a short access test session at the conclusion of the two-bottle test, blast rats fell into a bimodal distribution, and among high intake rats, blast treated animals had significantly elevated intake compared to shams. We found no effect of blast when rats were tested for an alcohol deprivation effect or compulsive drinking in a quinine adulteration test. Throughout the experiment, alcohol drinking was modest in both groups, consistent with other studies using Sprague Dawley rats. In conclusion, blast exposure had a minimal impact on overall alcohol intake in Sprague Dawley rats, although intake was increased in a subpopulation of blast animals in a short access session following intermittent access exposure. PMID:25910266

  10. [Effects of palmitic acid on activity of uncoupling proteins and proton leak in in vitro cerebral mitochondria from the rats exposed to simulated high altitude hypoxia].

    Science.gov (United States)

    Xu, Yu; Liu, Jun-Ze; Xia, Chen

    2008-02-25

    To reveal the roles of uncoupling proteins (UCPs) in disorder of mitochondrial oxidative phosphorylation induced by free fatty acid during hypoxic exposure, the effects of palmitic acid on activity of UCPs, proton leak and mitochondrial membrane potential in hypoxia-exposed rat brain mitochondria were observed in vitro. Adult Sprague-Dawley (SD) rats were set randomly into control, acute hypoxia and chronic hypoxia groups (n=8 in each group). The acute and chronic hypoxic rats were exposed to simulated 5000 m high altitude in a hypobaric chamber 23 h/d for 3 d and 30 d, respectively. The brain mitochondria were isolated by centrifugation. UCP content and activity were detected by [(3)H]-GTP binding method. The proton leak was measured by TPMP(+) electrode and oxygen electrode. The membrane potential of mitochondria was calculated by detecting the fluorescence from Rodamine 123. Hypoxic exposure resulted in an increase in UCP activity and content as well as proton leak, but a decrease in the membrane potential of rat brain mitochondria. Palmitic acid resulted in further increases in UCP activity and content as well as proton leak, and further decrease in membrane potential of brain mitochondria in vitro from hypoxia-exposed rats, but hypoxic exposure decreased the reactivity of cerebral mitochondria to palmitic acid, especially in the acute hypoxia group. There was a negative correlation between mitochondrial proton leak and K(d) value (representing derivative of UCP activity, PB(max) (representing the maximal content of UCPs in mitochondrial inner membrane, P<0.01, r = 0.856). Cerebral mitochondrial membrane potential was negatively correlated with proton leak (P<0.01, r = -0.880). It is suggested that hypoxia-induced proton leak enhancement and membrane potential decrease are correlated with the increased activity of UCPs. Hypoxia can also decrease the sensitivity of cerebral mitochondria to palmitic acid, which may be a self-protective mechanism in high altitude

  11. 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...

  12. Changes in neurotransmitter receptor expression levels in rat brain after 4-week exposure to 1-bromopropane.

    Science.gov (United States)

    Mohideen, Sahabudeen Sheik; Ichihara, Sahoko; Banu, Shameema; Liu, Fang; Kitoh, Junzoh; Ichihara, Gaku

    2009-11-01

    1-Bromopropane (1-BP), an alternative to ozone-depleting solvents, exhibits neurotoxicity and reproductive toxicity in animals and humans. The present study investigated the effects of exposure to 1-BP on expression of neurotransmitter receptor genes in the rat brain to explore possible biomarkers for central neurotoxicity and find brain regions sensitive for microarray analysis. Thirty-six F344 rats were divided at random into four equal groups of nine and exposed to 1-BP at 0, 400, 800 and 1000 ppm for 8 h/day; 7 days/week for 4 weeks. Total RNA from different brain regions was extracted and real-time PCR was conducted to quantify the mRNA levels of serotonin, dopamine and GABA receptors. Western blot analysis for specific regions of interest was also carried out to determine the protein levels. The mRNAs of 5HTr2a, D2R and GABAa1 were down regulated in a 1-BP dose-dependent manner in the hippocampus. The mRNA levels of 5HTr1a, 5HTr2a, D1R and GABAa1 were significantly decreased in the cortex of rats exposed to 800 ppm, but not to 1000 ppm. The mRNAs of 5HTr1a and 5HTr3a in the pons-medulla were decreased in rats exposed to 400 ppm or higher concentrations. The mRNA expression of D2R in the hippocampus and 5HTr1a and 5HTr3a in the pons-medulla oblongata were the most sensitive indicators of 1-BP neurotoxicity. The results suggest that mRNA expression analysis is useful in identifying brain regions susceptible to 1-BP, as well as providing potential biomarkers for central nervous system toxicity.

  13. Increased bone calcium dissociation in lead-exposed rats

    Directory of Open Access Journals (Sweden)

    Eko Suhartono

    2012-12-01

    Full Text Available Background Lead is still a major environmental and occupational health hazard, since it is extensively used in the production of paints, gasoline and cosmetics. This causes the metal to be ubiquitous in the environment, being found in the air, soil, and water, from which it can enter the human body by inhalation or ingestion. Absorbed lead is capable of altering the calcium levels in bone. The aim of this study was to demonstrate the effect of lead on bone calcium levels by measuring the reaction constant, Gibbs free energy, and enthalpy. Methods This study was of pure experimental design using 100 male albino rats (Rattus norvegicus. The experimental animals were assigned by simple randomization to two groups, one group receiving lead acetate orally at a dosage of 100 mg/kgBW, while the other group did not receive lead acetate. The intervention was given for 4 weeks and the rats were observed weekly for measurement of bone calcium levels by the permanganometric method. Results This study found that k1 (hydroxyapatite dissociation rate constant was 0.90 x 10-3 dt-1, and that k2 (hydroxyapatite association rate constant was 6.16 x 10-3 dt-1 for the control group, whereas for the intervention group k1 = 26.20 x 10-3 dt-1 and k2 = 16.75 x 10-3 dt-1. Thermodynamically, the overall reaction was endergonic and endothermic (DG > 0 and DH > 0. ConclusionS Lead exposure results in increased dissociation rate of bone in comparison with its association rate. Overall, the reaction was endergonic and endothermic (DG > 0 and DH > 0.

  14. Increased bone calcium dissociation in lead-exposed rats

    Directory of Open Access Journals (Sweden)

    Eko Suhartono

    2015-12-01

    Full Text Available BACKGROUND Lead is still a major environmental and occupational health hazard, since it is extensively used in the production of paints, gasoline and cosmetics. This causes the metal to be ubiquitous in the environment, being found in the air, soil, and water, from which it can enter the human body by inhalation or ingestion. Absorbed lead is capable of altering the calcium levels in bone. The aim of this study was to demonstrate the effect of lead on bone calcium levels by measuring the reaction constant, Gibbs free energy, and enthalpy. METHODS This study was of pure experimental design using 100 male albino rats (Rattus norvegicus. The experimental animals were assigned by simple randomization to two groups, one group receiving lead acetate orally at a dosage of 100 mg/ kgBW, while the other group did not receive lead acetate. The intervention was given for 4 weeks and the rats were observed weekly for measurement of bone calcium levels by the permanganometric method. RESULTS This study found that k1 (hydroxyapatite dissociation rate constant was 0.90 x 10-3 dt-1, and that k2 (hydroxyapatite association rate constant was 6.16 x 10-3 dt-1 for the control group, whereas for the intervention group k1 = 26.20 x 10-3 dt-1 and k2 = 16.75 x 10-3 dt-1. Thermodynamically, the overall reaction was endergonic and endothermic (ΔG > 0 and ΔH > 0. CONCLUSIONS Lead exposure results in increased dissociation rate of bone in comparison with its association rate. Overall, the reaction was endergonic and endothermic (ΔG > 0 and ΔH > 0.

  15. Two-Year Chronic Bioassay study of Rats Exposed to a 1.6 GHz Radiofrequency Signal.

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Larry E.; Sheen, David M.; Wilson, Bary W.; Grumbein, Sondra L.; Creim, Jeffrey A.; Sasser, Lyle B.

    2004-08-06

    The purpose of this study was to determine whether long-term exposure to a 1.6 GHz radiofrequency (RF) field would affect the incidence of cancer in Fischer 344 rats. Thirty-six timed-pregnant rats were randomly assigned to each of three treatment groups: two groups exposed to a far-field RF Iridium signal and a third group that was sham exposed. Exposures were chosen such that the brain SAR in the fetuses was 0.16 W/kg. Whole-body far-field exposures were initiated at 19 days of gestation and continued at 2 h/day, 7 days/week for dams and pups after parturition until weaning ({approx}23 days old). The offspring (700) of these dams were selected, 90 males and 90 females for each near-field treatment group, with SAR levels in the brain calculated to be as follows: (1) 1.6 W/kg, (2) 0.16 W/kg and (3) near-field sham controls with an additional 80 males and 80 females as shelf controls. Confining, head-first, near-field exposures of 2 h/day, 5 days/week were initiated when the offspring were 36 + 1 days old and continued until the rats were 2 years old. No statistically significant differences were observed among treatment groups for number of live pups/litter, survival index and weaning weights, nor were there differences in clinical signs or neoplastic lesions among the treatment groups. The percentages of animals surviving at the end of the near-field exposure were not different among the male groups. In females a significant decrease in survival time was observed for the case control group.

  16. Micronuclei rate and hypoxanthine phosphoribosyl transferase mutation in radon-exposed rats

    Institute of Scientific and Technical Information of China (English)

    Fengmei Cui; Saijun Fan; Mingjiang Hu; Jihua Nie; Hongmei Li; Jian Tong

    2008-01-01

    The genetic changes in rats with radon exposure were studied by the micronucleus technology and detection of hypoxanthine phosphoribosyl transferase (hprt) mutations.The rate of the micronuclei in peripheral blood lymphocytes and tracheal-bronchial epithelial cells in the radon-inhaled rats was higher than that of the controls (P < 0.05).A similar result was obtained from the hprt assay,which showed a higher mutation frequency in radon-exposed rats.Our results suggested that micronuclei rate and hprt deficiency could be used as biomarkers for the genetic changes with radon exposure.

  17. Dragon's blood may have radioprotective effects in radiation-induced rat brain injury.

    Science.gov (United States)

    Xin, Nian; Li, Yu-Juan; Li, Xu; Wang, Xiao; Li, Yan; Zhang, Xiao; Dai, Rong-Ji; Meng, Wei-Wei; Wang, Hai-Long; Ma, Hong; Schläppi, Michael; Deng, Yu-Lin

    2012-07-01

    Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis. It is a traditional medicinal that is used for wound healing and to stop bleeding. Its main biological activity appears to be from phenolic compounds found in Dragon's blood. In this study, the radioprotective effects of Dragon's blood were examined after whole brain irradiation of rats with either 100 MeV/u Carbon (12)C(6+) heavy ions or (60)Co γ-rays. The amounts of radiation-induced oxidative stress, inflammatory cytokines and apoptosis in irradiated rat brains were compared with and without Dragon's blood treatment. Compared to the "irradiation only" control group, the Dragon's blood treatment group significantly decreased malondialdehyde and hydrogen peroxide levels, and increased superoxide dismutase activity and glutathione levels induced by oxidative stress in radiation exposed rats (P Dragon's blood also significantly reduced radiation-induced inflammatory cytokines of tumor necrosis factor-α, interferon-γ and interleukin-6 levels (P Dragon's blood significantly increased expression of brain-derived neurophic factor and inhibited the expression of pro-apoptotic caspase 3 (P Dragon's blood significantly inhibited expression of the AP-1 transcription factor family members c-fos and c-jun proteins (P Dragon's blood has radioprotective properties in rat brains after both heavy ions and (60)Co γ-ray exposure.

  18. Waxholm Space atlas of the Sprague Dawley rat brain

    OpenAIRE

    Papp, Eszter A.; Trygve B. Leergaard; Calabrese, Evan; Johnson, G. Allan; Bjaalie, Jan G.

    2014-01-01

    Three-dimensional digital brain atlases represent an important new generation of neuroinformatics tools for understanding complex brain anatomy, assigning location to experimental data, and planning of experiments. We have acquired a microscopic resolution isotropic MRI and DTI atlasing template for the Sprague Dawley rat brain with 39 µm isotropic voxels for the MRI volume and 78 µm isotropic voxels for the DTI. Building on this template, we have delineated 76 major anatomical structures in ...

  19. Actin purification from a gel of rat brain extracts.

    Science.gov (United States)

    Levilliers, N; Peron-Renner, M; Coffe, G; Pudles, J

    1984-01-01

    Actin, 99% pure, has been recovered from rat brain with a high yield (greater than 15 mg/100 g brain). We have shown that: 1. a low ionic strength extract from rat brain tissue is capable of giving rise to a gel; 2. actin is the main gel component and its proportion is one order of magnitude higher than in the original extract; 3. actin can be isolated from this extract by a three-step procedure involving gelation, dissociation of the gel in 0.6 M KCl, followed by one or two depolymerization-polymerization cycles.

  20. Effects of glutamine pretreatment on learning and memory in heat-exposed rats

    Institute of Scientific and Technical Information of China (English)

    Shenghao Zhao; Lei Wang; Qin Wang; Siyi Wang; Chundi Deng; Xianfei Xie; Youe Yan; Hui Wang

    2008-01-01

    BACKGROUND: Glutamine (Gln) pretreatment can protect neural cells from injuries due to heat, ischemia, hypoxia, endotoxemia, and inflammatory factors.OBJECTIVE: To observe the effects of Gln pretreatment on learning and memory, survival time, and rectal temperature in heat-exposed rats.DESIGN, TIME AND SETTING: The present randomized grouping, neurobehavioral experiment was performed at the Laboratory of Department of Pharmacology, Basic School of Medicine, Wuhan University between March and September 2007.MATERIALS: Twenty-four healthy, Wistar rats were included in this study. SPX-160B biochemistry incubator (Shanghai Experimental Equipment Co., Ltd., China), probe electronic thermometer (11000 type, Maikepai Science and Technology Co., Ltd., China), Y-type maze box used in conjunction with MG-2 maze stimulator (Zhangjiagang Biomedical Instrument Factory, China), L-Gin (Batch No. 061218, 5 g/bottle, prepared into 10% aqueous solution, Amresco Company, USA) were used.METHODS: Twenty-four rats were randomly and evenly divided into 3 groups: heat-exposed, Gln low-lose, and Gln high-dose. Following learning and memory testing with the Y-maze, rats in the heat-exposed group were subjected to heat injury (40.5-41.5℃) in a biochemistry incubator. Rectal temperature was measured every 5 minutes. Thirty-five minutes after heat exposure, rats were removed and placed in the Y-type maze to test learning and memory again. Subsequently, the rats were returned to the same environment of thermal stimulation until they died. Rat survival time was recorded. Subsequent to learning and memory testing, rats in the Gln low-dose and high-dose groups received an i.p. injection of Gln (0.4 g/kg and 0.8 g/kg, respectively), and were exposed to heat injury. The remaining experimental procedures remained the same as for the heat-exposed group.MAIN OUTCOME MEASURES: Rat learning and memory, rectal temperature, and survival time in heat exposure environment.RESULTS: (1) In the Y

  1. Postnatal neurobehavioral development in rats exposed in utero to caffeine.

    Science.gov (United States)

    West, G L; Sobotka, T J; Brodie, R E; Beier, J M; O'Donnell, M W

    1986-01-01

    Potential behavioral and teratogenic effects of caffeine were studied in Charles River CD albino rats. Caffeine in distilled water was given by gavage to pregnant rats (dams) at doses of 5, 25, 50 or 75 mg/kg on Days 3-19 of gestation. Concurrent controls received distilled water gavage (10 ml/kg) on the same days. Dams were allowed to deliver normally. Physical and behavioral observations were made on dams during gestation and lactation and on F1 offspring through 9 weeks of age. Caffeine decreased body weights and food intake and increased water intake in gestating dams but these effects dissipated during lactation. Spontaneous locomotor activity (PAC) and open field (OF) were increased immediately after caffeine gavage but not before. Parturition was slightly delayed. With analyses of data based on individual pups the following effects were noted. Pre- and post-weaning offspring body weights were decreased in females at 50 and 75 mg/kg and in males at 75 mg/kg. Incisor eruption was delayed in females at 5, 50 and 75 mg/kg and in males at all doses. Auditory startle developed earlier in the 5 mg/kg dose group but was delayed at 75 mg/kg for males only. Eye opening was delayed in both sexes at 25, 50 and 75 mg/kg. In females, vaginal opening was delayed at 5, 25 and 75 mg/kg and 9-week ovary weights were increased at 75 mg/kg. In postweaning males, food intake was decreased and water intake was increased with increasing dose. In males, PAC was decreased at 75 mg/kg only on Day 12. At 7 weeks of age, step-down passive avoidance was decreased at 5 and 25 mg/kg but increased at 50 and 75 mg/kg, and at 8 weeks of age, shuttlebox active avoidance was decreased with increasing dose. Maternal and offspring behaviors were only weakly correlated. Correction for litter effect in developmental data yielded fewer significant results and only at 50 and 75 mg/kg. The issue of whether it is always appropriate to correct for "litter effect" is discussed.

  2. Autoradiographic visualization of insulin-like growth factor-II receptors in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Mendelsohn, L.G.; Kerchner, G.A.; Clemens, J.A.; Smith, M.C.

    1986-03-01

    The documented presence of IGF-II in brain and CSF prompted us to investigate the distribution of receptors for IGF-II in rat brain slices. Human /sup 125/-I-IGF-II (10 pM) was incubated for 16 hrs at 4/sup 0/C with slide-mounted rat brain slices in the absence and presence of unlabeled human IGF-II (67 nM) or human insulin (86 nM). Slides were washed, dried, and exposed to X-ray film for 4-7 days. The results showed dense labeling in the granular layers of the olfactory bulbs, deep layers of the cerebral cortex, pineal gland, anterior pituitary, hippocampus (pyramidal cells CA/sub 1/-CA/sub 2/ and dentate gyrus), and the granule cell layers of the cerebellum. Unlabeled IGF-II eliminated most of the binding of these brain regions while insulin produced only a minimal reduction in the amount of /sup 125/I-IGF-II bound. These results indicate that a specific neural receptor for IGS-II is uniquely distributed in rat brain tissue and supports the notion that this peptide might play an important role in normal neuronal functioning.

  3. 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.

  4. Detection of Low Level Microwave Radiation Induced Deoxyribonucleic Acid Damage Vis-à-vis Genotoxicity in Brain of Fischer Rats

    Science.gov (United States)

    Deshmukh, Pravin Suryakantrao; Megha, Kanu; Banerjee, Basu Dev; Ahmed, Rafat Sultana; Chandna, Sudhir; Abegaonkar, Mahesh Pandurang; Tripathi, Ashok Kumar

    2013-01-01

    Background: Non-ionizing radiofrequency radiation has been increasingly used in industry, commerce, medicine and especially in mobile phone technology and has become a matter of serious concern in present time. Objective: The present study was designed to investigate the possible deoxyribonucleic acid (DNA) damaging effects of low-level microwave radiation in brain of Fischer rats. Materials and Methods: Experiments were performed on male Fischer rats exposed to microwave radiation for 30 days at three different frequencies: 900, 1800 and 2450 MHz. Animals were divided into 4 groups: Group I (Sham exposed): Animals not exposed to microwave radiation but kept under same conditions as that of other groups, Group II: Animals exposed to microwave radiation at frequency 900 MHz at specific absorption rate (SAR) 5.953 × 10−4 W/kg, Group III: Animals exposed to 1800 MHz at SAR 5.835 × 10−4 W/kg and Group IV: Animals exposed to 2450 MHz at SAR 6.672 × 10−4 W/kg. At the end of the exposure period animals were sacrificed immediately and DNA damage in brain tissue was assessed using alkaline comet assay. Results: In the present study, we demonstrated DNA damaging effects of low level microwave radiation in brain. Conclusion: We concluded that low SAR microwave radiation exposure at these frequencies may induce DNA strand breaks in brain tissue. PMID:23833433

  5. The Effect of Hypericum Perforarum on Anxiety and Depressant Activity in Wistar Rats Exposed to Phenol

    Directory of Open Access Journals (Sweden)

    M Modhej

    2015-02-01

    Results: The statistic findings indicated that there were no significant differences between behavior tests with respect to the treatments (P> 0.05. Conclusion: The study results proposed that the used levels of Hypericum Perforarum extract did not show any significant effects on reduction of anxious and depressant behaviors in phenol exposed Wistar rats.

  6. Histopathological changes in Wistar albino rats exposed to aqueous extract of unripe Carica papaya

    Directory of Open Access Journals (Sweden)

    Taofeeq Oduola

    2010-05-01

    Full Text Available Background: Exposure of animals to xenobiotics may or may not trigger adverse response at cellular levels. Aqueous extract of unripe Carica papaya is consumed by sickle cell patients as antisickling agent in Western Nigeria. Aim: This study was undertaken to investigate the effects of Carica papaya on certain organs in Wister albino rats exposed to aqueous extract of unripe Carica papaya. Materials and Methods: Different doses of aqueous extract of unripe Carica papaya were administered orally daily for 42 days to six groups of rats. At the end of exposure, the animals were sacrificed and tissue sections were prepared from livers, kidneys, hearts and small intestines using standard techniques. Results: Histopathological results showed that no pathological changes were observed in tissue sections of experimental animals when compared with tissue sections of the same organs in control animals. Conclusion: No pathological changes were elicited in the organs of rats exposed to aqueous extract of unripe Carica papaya.

  7. Effect of Electromagnetic Pulse Exposure on Brain Micro Vascular Permeability in Rats

    Institute of Scientific and Technical Information of China (English)

    GUI-RONG DING; KANG-CHU LI; XIAO-WU WANG; YONG-CHUN ZHOU; LIAN-BO QIU; JUAN TAN; SHENG-LONG XU; GUO-ZHEN GUO

    2009-01-01

    Objective To observe the effect of electromagnetic pulse (EMP) exposure on cerebral micro vascular permeability in rats.Methods The whole-body of male Sprague-Dawley rats were exposed or sham exposed to 200 pulses or 400 pulses (1 Hz) of EMP at 200 kV/m.At 0.5,1,3,6,and 12 h after EMP exposure,the permeability of cerebral micro vascular was detected by transmission electron microscopy and immunohistochemistry using lanthanum nitrate and endogenous albumin as vascular tracers,respectively. Results The lanthanum nitrate tracer was limited to the micro vascular lumen with no lanthanum nitrate or albumin tracer extravasation in control rat brain.After EMP exposure,the lanthanum nitrate ions reached the tight junction,basal lamina and pericapillary tissue.Similarly,the albumin immunopositive staining was identified in pericapillary tissue.The changes in brain micro vascular permeability were transient,the leakage of micro vascular vessels appeared at 1 h,and reached its peak at 3 h,and nearly recovered at 12 h,after EMP exposure.In addition,the leakage of micro vascular was more obvious after exposure of EMP at 400 pulses than after exposure of EMP at 200 pulses. Conclusion Exposure to 200 and 400 pulses (1 Hz) of EMP at 200 kV/m can increase cerebral micro vascular permeability in rats,which is recoverable.

  8. Aggregation in quads but not pairs of rats exposed to cat odor or bright light.

    Science.gov (United States)

    Bowen, Michael T; Keats, Kirily; Kendig, Michael D; Cakic, Vince; Callaghan, Paul D; McGregor, Iain S

    2012-07-01

    In many prey species aggregation of individuals is a defensive strategy commonly employed in response to predators and predator-related cues. However, very little work has explored this adaptive response in laboratory rats. It is known that individual rats show characteristic defensive responses to predator odors, such as hiding, avoidance, inhibition of foraging, feeding and reproduction, and risk assessment directed toward the odor source. However, whether these species-typical responses in individuals are altered in the presence of other conspecifics is yet to be characterized. The present study therefore examined the defensive response of groups of two rats (dyads) or four rats (quads) to two unconditioned stressors: bright ambient light and cat odor (a 2g ball of cat fur). The dyads and quads were formed from familiar cage mates and test sessions (20 min) occurred in a large open arena (1200 mm(2)) to which the rats had been extensively habituated under dark conditions. The results showed that when quads of rats were exposed to either cat odor or bright light in this arena, they showed characteristic increases in close social proximity, termed "huddling". A tight grouping of 3 (triplet) or 4 (quad) rats was commonly seen in response to cat fur, while triplets were more commonly seen in response to bright light. Interestingly there was no evidence for increased social proximity in dyads exposed to either stressor, only in quads. However, cat odor caused other signs of fear (such as decreased locomotor activity and increased defecation) in both quads and dyads. It is concluded that huddling is a rodent defensive strategy in rats when anxiogenic stimuli are encountered by larger groups of rats. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-03-01

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

  10. Acute death of astrocytes in blast-exposed rat organotypic hippocampal slice cultures

    Science.gov (United States)

    Miller, Anna P.; Shah, Alok S.; Aperi, Brandy V.; Kurpad, Shekar N.; Stemper, Brian D.; Glavaski-Joksimovic, Aleksandra

    2017-01-01

    Blast traumatic brain injury (bTBI) affects civilians, soldiers, and veterans worldwide and presents significant health concerns. The mechanisms of neurodegeneration following bTBI remain elusive and current therapies are largely ineffective. It is important to better characterize blast-evoked cellular changes and underlying mechanisms in order to develop more effective therapies. In the present study, our group utilized rat organotypic hippocampal slice cultures (OHCs) as an in vitro system to model bTBI. OHCs were exposed to either 138 ± 22 kPa (low) or 273 ± 23 kPa (high) overpressures using an open-ended helium-driven shock tube, or were assigned to sham control group. At 2 hours (h) following injury, we have characterized the astrocytic response to a blast overpressure. Immunostaining against the astrocytic marker glial fibrillary acidic protein (GFAP) revealed acute shearing and morphological changes in astrocytes, including clasmatodendrosis. Moreover, overlap of GFAP immunostaining and propidium iodide (PI) indicated astrocytic death. Quantification of the number of dead astrocytes per counting area in the hippocampal cornu Ammonis 1 region (CA1), demonstrated a significant increase in dead astrocytes in the low- and high-blast, compared to sham control OHCs. However only a small number of GFAP-expressing astrocytes were co-labeled with the apoptotic marker Annexin V, suggesting necrosis as the primary type of cell death in the acute phase following blast exposure. Moreover, western blot analyses revealed calpain mediated breakdown of GFAP. The dextran exclusion additionally indicated membrane disruption as a potential mechanism of acute astrocytic death. Furthermore, although blast exposure did not evoke significant changes in glutamate transporter 1 (GLT-1) expression, loss of GLT-1-expressing astrocytes suggests dysregulation of glutamate uptake following injury. Our data illustrate the profound effect of blast overpressure on astrocytes in OHCs at 2 h

  11. Non-signalling energy use in the developing rat brain.

    Science.gov (United States)

    Engl, Elisabeth; Jolivet, Renaud; Hall, Catherine N; Attwell, David

    2017-03-01

    Energy use in the brain constrains its information processing power, but only about half the brain's energy consumption is directly related to information processing. Evidence for which non-signalling processes consume the rest of the brain's energy has been scarce. For the first time, we investigated the energy use of the brain's main non-signalling tasks with a single method. After blocking each non-signalling process, we measured oxygen level changes in juvenile rat brain slices with an oxygen-sensing microelectrode and calculated changes in oxygen consumption throughout the slice using a modified diffusion equation. We found that the turnover of the actin and microtubule cytoskeleton, followed by lipid synthesis, are significant energy drains, contributing 25%, 22% and 18%, respectively, to the rate of oxygen consumption. In contrast, protein synthesis is energetically inexpensive. We assess how these estimates of energy expenditure relate to brain energy use in vivo, and how they might differ in the mature brain.

  12. Effects of GSM modulated radio-frequency electromagnetic radiation on permeability of blood-brain barrier in male & female rats.

    Science.gov (United States)

    Sırav, Bahriye; Seyhan, Nesrin

    2016-09-01

    With the increased use of mobile phones, their biological and health effects have become more important. Usage of mobile phones near the head increases the possibility of effects on brain tissue. This study was designed to investigate the possible effects of pulse modulated 900MHz and 1800MHz radio-frequency radiation on the permeability of blood-brain barrier of rats. Study was performed with 6 groups of young adult male and female wistar albino rats. The permeability of blood-brain barrier to intravenously injected evans blue dye was quantitatively examined for both control and radio-frequency radiarion exposed groups. For male groups; Evans blue content in the whole brain was found to be 0.08±0.01mg% in the control, 0.13±0.03mg% in 900MHz exposed and 0.26±0.05mg% in 1800MHz exposed animals. In both male radio-frequency radiation exposed groups, the permeability of blood-brain barrier found to be increased with respect to the controls (pradio-frequency radiation exposure was found more effective on the male animals (p0.01). However 900MHz pulse modulated radio-frequency exposure was found effective on the permeability of blood-brain barrier of female animals. Results have shown that 20min pulse modulated radio-frequency radiation exposure of 900MHz and 1800MHz induces an effect and increases the permeability of blood-brain barrier of male rats. For females, 900MHz was found effective and it could be concluded that this result may due to the physiological differences between female and male animals. The results of this study suggest that mobile phone radation could lead to increase the permeability of blood-brain barrier under non-thermal exposure levels. More studies are needed to demonstrate the mechanisms of that breakdown.

  13. Behavior, physiology, and energy deposition in rats chronically exposed to 2450-MHz radiation

    Energy Technology Data Exchange (ETDEWEB)

    D' Andrea, J.A.; Gandhi, O.P.

    1987-11-01

    The research program was initiated to determine both the specific absorption rate (SAR) and the behavioral and physiological consequences of chronic c-w microwave radiation exposure at 2450 MHz in the laboratory rat. Whole-body average and local SARs at discrete sites within the body of rats and mice were determined experimentally using different exposure systems and analytical techniques. The whole-body average SAR and the distribution of SAR within the body depends on a variety of factors: type of exposure system, polarization of the field, size of the animal, and angle of radiation incident on the body. Three experiments were conducted to determine the effects of chronic exposure to 2450-MHz microwave radiation on several measures of rat behavior and physiology. Groups of rats were exposed intermittently to 2450-MHz radiation at power densities of 0.5 mW/sq. cm. or 2.5 mW/sq. cm. for 90 days.

  14. Does melatonin influence the apoptosis in rat uterus of animals exposed to continuous light?

    Science.gov (United States)

    Ferreira, Cecília S; Carvalho, Kátia C; Maganhin, Carla C; Paiotti, Ana P R; Oshima, Celina T F; Simões, Manuel J; Baracat, Edmund C; Soares, José M

    2016-02-01

    Melatonin has been described as a protective agent against cell death and oxidative stress in different tissues, including in the reproductive system. However, the information on the action of this hormone in rat uterine apoptosis is low. Our objective was to evaluate the effects of melatonin on mechanisms of cell death in uterus of rats exposed to continuous light stress. Twenty adult Wistar rats were divided into two groups: GContr (vehicle control) and GExp which were treated with melatonin (0.4 mg/mL), both were exposed to continuous light for 90 days. The uterus was removed and processed for quantitative real time PCR (qRT-PCR), using PCR-array plates of the apoptosis pathway; for immunohistochemistry and TUNEL. The results of qRT-PCR of GEXP group showed up-regulation of 13 and 7, pro-apoptotic and anti-apoptotic genes, respectively, compared to GContr group. No difference in pro-apoptotic proteins (Bax, Fas and Faslg) expression was observed by immunohistochemistry, although the number of TUNEL-positive cells was lower in the group treated with melatonin compared to the group not treated with this hormone. Our data suggest that melatonin influences the mechanism and decreases the apoptosis in uterus of rats exposed to continuous light.

  15. [Protective effect of salidroside against high altitude hypoxia-induced brain injury in rats].

    Science.gov (United States)

    Dong, Xiaoru; Zhang, Xiangnan; Li, Dan; Li, Bin; Wang, Jiye; Meng, Shanshan; Luo, Wenjing; Zhang, Wenbin

    2015-10-01

    To observe the protective effect of salidroside against brain injury in rats exposed to hypobaric hypoxia, and investigate the molecular mechanism of salidroside in the prevention of hypobaric hypoxia-induced brain injury. Rats were placed in experiment module simulating 6000 m altitude to establish acute hypobaric hypoxia-induced brain injury models. Their respiratory frequency was observed and recorded. Cell apoptosis in the hippocampal dentate gyrus (DG) was detected by TUNEL assay; the expressions of Ras homolog family member A (RhoA), phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected by Western blotting. After acute exposure to 6000 m altitude, the respiratory frequency of the rats increased remarkably. The simulation of hypobaric hypoxia induced cell apoptosis in hippocampal DG region, and salidroside intervention inhibited the process of cell apoptosis. The expressions of RhoA, p-ERK, p-JNK decreased after hypobaric hypoxia exposure. Salidroside intervention reversed RhoA expression and raised the levels of p-ERK and p-JNK. Acute exposure to hypobaric hypoxia can induce cell apoptosis in rat hippocampal DG, and salidroside can protect the cells from the exposure-induced apoptosis.

  16. Uterine phenotype of young adult rats exposed to dietary soy or genistein during development.

    Science.gov (United States)

    Eason, Renea R; Till, S Reneé; Velarde, Michael C; Geng, Yan; Chatman, Leon; Gu, Liwei; Badger, Thomas M; Simmen, Frank A; Simmen, Rosalia C M

    2005-10-01

    Dietary soy intake is associated with protection from breast cancer, but questions persist on the potential risks of the major soy isoflavone genistein (GEN) on female reproductive health. Here, we evaluated intermediate markers of cancer risk in uteri of cycling, young adult Sprague-Dawley rats lifetime exposed to one of three AIN-93G semipurified diets: casein (CAS), soy protein isolate (SPI+ with 276 mg GEN aglycone equivalents/kg) and CAS+GEN (GEN at 250 mg/kg). Postnatal day 50 (PND50) rats lifetime exposed to GEN or SPI+ had similar uterine luminal epithelium height, myometrial thickness, endometrial gland numbers, endometrial immunoreactive proliferating cell nuclear antigen (PCNA), and serum estrogen and progesterone, as CAS-fed rats. GEN-fed rats showed modestly increased apoptosis in uterine glandular epithelium, compared to those of CAS- or SPI+-fed groups. Diet had no effect on the uterine expression of genes for the tumor suppressors PTEN, p53 and p21, and the apoptotic-associated proteins Bcl2, Bax and progesterone receptor. Uterine tissue and serum concentrations of total GEN were higher in rats fed GEN than in those fed SPI+. Human Ishikawa endocarcinoma cells treated with GEN-fed rat serum tended to exhibit increased apoptotic status than those treated with CAS-fed rat serum. Exogenously added GEN (0.2 and 2 microM) increased, while estradiol-17beta (0.1 microM) decreased Ishikawa cell apoptosis, relative to untreated cells. Results suggest that lifetime dietary exposure to soy foods does not alter uterine cell phenotype in young adult rats, while GEN, by enhancing uterine endometrial glandular apoptosis in vivo and in vitro, may confer protection against uterine carcinoma. Given its limited influence on uterine phenotype of young adult females, GEN, when taken as part of soy foods or as supplement, should be favorably considered for other potential health benefits.

  17. Succimer chelation normalizes reactivity to reward omission and errors in lead-exposed rats.

    Science.gov (United States)

    Beaudin, Stéphane A; Stangle, Diane E; Smith, Donald R; Levitsky, David A; Strupp, Barbara J

    2007-01-01

    This study evaluated the efficacy of a 3-week course of succimer treatment to alleviate behavioral deficits in rats exposed to lead (Pb) for the first 4 weeks of life. A 3 x 2 factorial design was used: three levels of lead exposure (No Pb, Moderate, and High Pb) and two levels of chelation (succimer or vehicle). Behavioral testing was conducted following chelation therapy, from 2 to 9 months of age; this report presents the results of two of the administered tasks: (1) a conditional olfactory discrimination task (baseline task), and (2) a conditional olfactory discrimination task with periodic reward omission on some correct trials (RO task). In the RO task, the performance disruption produced by committing an error on the previous trial was significantly greater for both unchelated lead-exposed groups than for controls. The High Pb rats were also more sensitive to reward omission than controls, providing converging evidence for impaired regulation of arousal or emotion. Importantly, succimer treatment was effective in normalizing the heightened reactivity of the lead-exposed animals to both errors and reward omission. In addition, non-lead-exposed rats that were treated with succimer tended to be more affected by a prior error than controls in their latency to respond on post-error trials. In sum, these findings provide new evidence that succimer chelation can significantly lessen the lasting neurobehavioral dysfunction produced by early lead exposure, but also suggest that there may be risks of administering the drug to individuals without elevated blood lead levels.

  18. Protective effect of bacoside A on cigarette smoking-induced brain mitochondrial dysfunction in rats.

    Science.gov (United States)

    Anbarasi, Kothandapani; Vani, Ganapathy; Devi, Chennam Srinivasulu Shyamala

    2005-01-01

    Chronic exposure to cigarette smoke affects the structure and function of mitochondria, which may account for the pathogenesis of smoking-related diseases. Bacopa monniera Linn., used in traditional Indian medicine for various neurological disorders, was shown to possess mitrochondrial membrane-stabilizing properties in the rat brain during exposure to morphine. We investigated the protective effect of bacoside A, the active principle of Bacopa monniera, against mitochondrial dysfunction in rat brain induced by cigarette smoke. Male Wistar albino rats were exposed to cigarette smoke and administered bacoside A for a period of 12 weeks. The mitochondrial damage in the brain was assessed by examining the levels of lipid peroxides, cholesterol, phospholipid, cholesterol/phospholipid (C/P) ratio, and the activities of isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase, and cytochrome C oxidase. The oxidative phosphorylation (rate of succinate oxidation, respiratory control ratio and ADP/O ratio, and the levels of ATP) was evaluated for the assessment of mitochondrial functional capacity. We found significantly elevated levels of lipid peroxides, cholesterol, and C/P ratio, and decreased levels of phospholipids and mitochondrial enzymes in the rats exposed to cigarette smoke. Measurement of oxidative phosphorylation revealed a marked depletion in all the variables studied. Administration of bacoside A prevented the structural and functional impairment of mitochondria upon exposure to cigarette smoke. From the results, we suggest that chronic cigarette smoke exposure induces damage to the mitochondria and that bacoside A protects the brain from this damage by maintaining the structural and functional integrity of the mitochondrial membrane.

  19. Effect of a chronic GSM 900 MHz exposure on glia in the rat brain.

    Science.gov (United States)

    Ammari, Mohamed; Brillaud, Elsa; Gamez, Christelle; Lecomte, Anthony; Sakly, Mohsen; Abdelmelek, Hafedh; de Seze, René

    2008-01-01

    Extension of the mobile phone technology raises concern about the health effects of 900 MHz microwaves on the central nervous system (CNS). In this study we measured GFAP expression using immunocytochemistry method, to evaluate glial evolution 10 days after a chronic exposure (5 days a week for 24 weeks) to GSM signal for 45 min/day at a brain-averaged specific absorption rate (SAR)=1.5 W/kg and for 15 min/day at a SAR=6 W/kg in the following rat brain areas: prefrontal cortex (PfCx), caudate putamen (Cpu), lateral globus pallidus of striatum (LGP), dentate gyrus of hippocampus (DG) and cerebellum cortex (CCx). In comparison to sham or cage control animals, rats exposed to chronic GSM signal at 6 W/kg have increased GFAP stained surface areas in the brain (pGSM at 1.5 W/kg did not increase GFAP expression. Our results indicated that chronic exposure to GSM 900 MHz microwaves (SAR=6 W/kg) may induce persistent astroglia activation in the rat brain (sign of a potential gliosis).

  20. Thermoregulation in cold- and noncold-acclimated rats cold exposed in hypergravic fields

    Science.gov (United States)

    Horowitz, J. M.; Horwitz, B. A.; Monson, C. B.

    1983-01-01

    The effect of hypergravity on thermoregulation processes is investigated experimentally in rats. Hooded male Long-Evans rats were kept for 6 weeks at 5 or 23 C (cold-acclimated and noncold-acclimated groups, CA and NCA) prior to testing. One test protocol comprised sequential 1-h exposures to 23 C at 1 G, 23 C at 3 G (in a 2.1-m radius centrifuge; -Gx), 8 C at 3 G, 8 C at 1 G, and finally 23 C at 1 G, with continuous measurement of the oxygen consumption. In a second protocol, restrained rats were exposed to 23 C at 1 G, 23 C at 3 G, and 10 C at 3 G, and core temperature changes were monitored. The results are presented in graphs and a table. Oxygen consumption doubled in both CA and NCA rats on exposure to cold at 1 G, but at 3 G NCA consumption decreased while CA consumption remained high. The CA rats were also more able to maintain core temperature at 3 G than the NCA rats. These differences are attributed to the nonshivering thermogenic processes developed in CA rats, which appear to be unaffected by hypergravity.

  1. Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid

    Directory of Open Access Journals (Sweden)

    Angel A. Puig-Lagunes

    2016-11-01

    Full Text Available Background Epidemiological evidence indicates epilepsy is more common in patients with autism spectrum disorders (ASD (20–25% than in the general population. The aim of this project was to analyze seizure susceptibility in developing rats prenatally exposed to valproic acid (VPA as autism model. Methods Pregnant females were injected with VPA during the twelfth embryonic day. Seizures were induced in fourteen-days-old rat pups using two models of convulsions: pentylenetetrazole (PTZ and lithium-pilocarpine (Li-Pilo. Results Two subgroups with different PTZ-induced seizure susceptibility in rats exposed to VPA were found: a high susceptibility (VPA+ (28/42, seizure severity 5 and a low susceptibility (VPA− (14/42, seizure severity 2. The VPA+ subgroup exhibited an increased duration of the generalized tonic-clonic seizure (GTCS; 45 ± 2.7 min, a higher number of rats showed several GTCS (14/28 and developed status epilepticus (SE after PTZ injection (19/27 compared with control animals (36.6 ± 1.9 min; 10/39; 15/39, respectively. No differences in seizure severity, latency or duration of SE induced by Li-Pilo were detected between VPA and control animals. Discussion Prenatal VPA modifies the susceptibility to PTZ-induced seizures in developing rats, which may be linked to an alteration in the GABAergic transmission. These findings contribute to a better understanding of the comorbidity between autism and epilepsy.

  2. Fibrinogen α-chain-derived peptide is upregulated in hippocampus of rats exposed to acute morphine injection and spontaneous alternation testing.

    Science.gov (United States)

    Maki, Agatha E; Morris, Kenneth A; Catherman, Kasia; Chen, Xian; Hatcher, Nathan G; Gold, Paul E; Sweedler, Jonathan V

    2014-06-01

    Fibrinogen is a secreted glycoprotein that is synthesized in the liver, although recent in situ hybridization data support its expression in the brain. It is involved in blood clotting and is released in the brain upon injury. Here, we report changes in the extracellular levels of fibrinogen α-chain-derived peptides in the brain after injections of saline and morphine. More specifically, in order to assess hippocampus-related working memory, an approach pairing in vivo microdialysis with mass spectrometry was used to characterize extracellular peptide release from the hippocampus of rats in response to saline or morphine injection coupled with a spontaneous alternation task. Two fibrinopeptide A-related peptides derived from the fibrinogen α-chain-fibrinopeptide A (ADTGTTSEFIEAGGDIR) and a fibrinopeptide A-derived peptide (DTGTTSEFIEAGGDIR)-were shown to be consistently elevated in the hippocampal microdialysate. Fibrinopeptide A was significantly upregulated in rats exposed to morphine and spontaneous alternation testing compared with rats exposed to saline and spontaneous alternation testing (P morphine alone (P morphine and a memory task suggests that a complex interaction between fibrinogen and morphine takes place in the hippocampus.

  3. Histopathological examinations of rat brains after long-term exposure to GSM-900 mobile phone radiation.

    Science.gov (United States)

    Grafström, Gustav; Nittby, Henrietta; Brun, Arne; Malmgren, Lars; Persson, Bertil R R; Salford, Leif G; Eberhardt, Jacob

    2008-11-25

    In order to mimic the real life situation, with often life-long exposure to the electromagnetic fields emitted by mobile phones, we have investigated in a rat model the effects of repeated exposures under a long period to Global System for Mobile Communication-900 MHz (GSM-900) radiation. Out of a total of 56 rats, 32 were exposed once weekly in a 2-h period, for totally 55 weeks, at different average whole-body specific absorption rates (SAR) (of in average 0.6 and 60 mW/kg at the initiation of the experimental period). The animals were exposed in a transverse electromagnetic transmission line chamber (TEM-cell) to radiation emitted by a GSM-900 test phone. Sixteen animals were sham exposed and eight animals were cage controls, which never left the animal house. After behavioural tests, 5-7 weeks after the last exposure, the brains were evaluated for histopathological alterations such as albumin extravasation, dark neurons, lipofuscin aggregation and signs of cytoskeletal and neuritic neuronal changes of the type seen in human ageing. In this study, no significant alteration of any these histopathological parameters was found, when comparing the GSM exposed animals to the sham exposed controls.

  4. ALA-PDT of glioma cell micro-clusters in BD-IX rat brain

    Science.gov (United States)

    Madsen, Steen J.; Angell-Petersen, Even; Spetalen, Signe; Carper, Stephen W.; Ziegler, Sarah A.; Hirschberg, Henry

    2006-02-01

    A significant contributory factor to the poor prognosis of patients with glioblastoma multiforme is the inability of conventional treatments to eradicate infiltrating glioma cells. A syngeneic rat brain tumor model is used to investigate the effects of aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on small clusters of tumor cells sequestered in normal brain. The intrinsic sensitivity of rat glioma cells to PDT was investigated by exposing ALA-incubated cells to a range of radiant exposures and irradiances using 635 nm light. Biodistribution studies were undertaken on tumor-bearing animals in order to determine the tumor selectivity of the photosensitizer following systemic administration (i.p.) of ALA. Effects of ALA-PDT on normal brain and gross tumor were evaluated using histopathology. Effects of PDT on isolated glioma cells in normal brain were investigated by treating animals 48 h after tumor cell implantation: a time when the micro-clusters of cells are protected by an intact blood-brain-barrier (BBB). Rat glioma cells in monolayer are susceptible to ALA-PDT - lower irradiances are more effective than higher ones. Fluorescence microscopy of frozen tissue sections showed that photosensitizer is produced with better than 200:1 tumor-to-normal tissue selectivity following i.p. ALA administration. ALA-PDT resulted in significant damage to both gross tumor and normal brain, however, the treatment failed to prolong survival of animals with newly implanted glioma cells compared to non-treated controls if the drug was delivered either i.p. or directly into the brain. In contrast, animals inoculated with tumor cells pre-incubated in vitro with ALA showed a significant survival advantage in response to PDT.

  5. Neuroglobin expression in rats after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Xin Lin; Min Li; Aijia Shang; Yazhuo Hu; Xiao Yang; Ling Ye; Suyan Bian; Zhongfeng Wang; Dingbiao Zhou

    2012-01-01

    In this study, we used a rat model of severe closed traumatic brain injury to explore the relationship between neuroglobin, brain injury and neuronal apoptosis. Real-time PCR showed that neuroglobin mRNA expression rapidly increased in the rat cerebral cortex, and peaked at 30 minutes and 48 hours following traumatic brain injury. Immunohistochemical staining demonstrated that neuroglobin expression increased and remained high 2 hours to 5 days following injury. The rate of increase in the apoptosis-related Bax/Bcl-2 ratio greatly decreased between 30 minutes and 1 hour as well as between 48 and 72 hours post injury. Expression of neuroglobin and the anti-apoptotic factor Bcl-2 greatly increased, while that of the proapoptotic factor decreased, in the cerebral cortex post severe closed traumatic brain injury. It suggests that neuroglobin might protect neurons from apoptosis after traumatic injury by regulating Bax/Bcl-2 pathway.

  6. Maternal L-Carnitine Supplementation Improves Brain Health in Offspring from Cigarette Smoke Exposed Mothers.

    Science.gov (United States)

    Chan, Yik Lung; Saad, Sonia; Al-Odat, Ibrahim; Oliver, Brian G; Pollock, Carol; Jones, Nicole M; Chen, Hui

    2017-01-01

    Maternal cigarette smoke exposure (SE) causes detrimental changes associated with the development of chronic neurological diseases in the offspring as a result of oxidative mitochondrial damage. Maternal L-Carnitine administration has been shown to reduce renal oxidative stress in SE offspring, but its effect in the brain is unknown. Here, we investigated the effects of maternal L-Carnitine supplementation on brain markers of oxidative stress, autophagy, mitophagy and mitochondrial energy producing oxidative phosphorylation (OXPHOS) complexes in SE offspring. Female Balb/c mice (8 weeks) were exposed to cigarette smoke prior to mating, during gestation and lactation with or without L-Carnitine supplementation (1.5 mM in drinking water). In 1 day old male SE offspring, brain mitochondrial damage was suggested by increased mitochondrial fusion and reduced autophagosome markers; whereas at 13 weeks, enhanced brain cell damage was suggested by reduced fission and autophagosome markers, as well as increased apoptosis and DNA fragmentation markers, which were partially reversed by maternal L-Carnitine supplementation. In female SE offspring, enhanced mitochondrial regeneration was suggested by decreased fission and increased fusion markers at day 1. At 13 weeks, there was an increase in brain energy demand, oxidative stress and mitochondrial turnover, reflected by the protein changes of OXPHOS complex, fission and autophagosome markers, as well as the endogenous antioxidant, which were also partially normalized by maternal L-Carnitine supplementation. However, markers of apoptosis and DNA fragmentation were not significantly changed. Thus L-Carnitine supplementation may benefit the brain health of the offspring from smoking mothers.

  7. Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction

    Directory of Open Access Journals (Sweden)

    Yali Xu

    2016-01-01

    Full Text Available Objective. Blood-brain barrier (BBB is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p<0.01. Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4±1, grade 2 while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

  8. Endocrine disrupting effects in rats perinatally exposed to a dietary relevant mixture of phytoestrogens.

    Science.gov (United States)

    Boberg, Julie; Mandrup, Karen Riiber; Jacobsen, Pernille Rosenskjold; Isling, Louise Krag; Hadrup, Niels; Berthelsen, Line; Elleby, Anders; Kiersgaard, Maria; Vinggaard, Anne Marie; Hass, Ulla; Nellemann, Christine

    2013-09-01

    Dietary phytoestrogens may prevent certain human diseases, but endocrine activity has been reported in animal studies. Sprague-Dawley rats were exposed perinatally to a 1-, 10- or 100-fold "high human dietary intake" mixture of 12 phytoestrogens consisting of mainly the lignan secoisolarici resinol and the isoflavones genistein and daidzein. This mixture induced persistent adverse effects, as adult male mammary glands showed hypertrophic growth. A reduced anogenital distance in newborn males indicated an anti-androgenic mode of action. Testosterone levels, testis and prostate weights, and expression of selected genes in testis and prostate were unaffected. Decreased serum estradiol was seen in genistein-exposed dams. This study indicated adverse effects at high intake levels in rats, but does not provide evidence for risk of phytoestrogen-mediated endocrine disruption at normal human dietary consumption levels. Further studies are warranted to increase the knowledge upon which risk assessment on dietary phytoestrogen exposure during pregnancy and infancy is based.

  9. Influence of trans fat on skin damage in first-generation rats exposed to UV radiation.

    Science.gov (United States)

    Barcelos, Raquel Cristine S; Vey, Luciana T; Segat, Hecson Jesser; Benvegnú, Dalila M; Trevizol, Fabíola; Roversi, Karine; Roversi, Katiane; Dias, Verônica T; Dolci, Geisa S; Kuhn, Fábio T; Piccolo, Jaqueline; CristinaVeit, Juliana; Emanuelli, Tatiana; Bürger, Marilise E

    2015-01-01

    The influence of trans fatty acids (TFA) on lipid profile, oxidative damage and mitochondrial function in the skin of rats exposed to ultraviolet radiation (UVR) was assessed. The first-generation offspring of female Wistar rats supplemented from pregnancy with either soybean oil (C-SO, rich in n-6 FA; control group) or hydrogenated vegetable fat (HVF, rich in TFA) were continued with the same supplements until adulthood, when half of each group was exposed to UVR for 12 weeks. The HVF group showed higher TFA cutaneous incorporation, increased protein carbonyl (PC) levels, decreased functionality of mitochondrial enzymes and antioxidant defenses of the skin. After UVR, the HVF group showed increased skin thickness and reactive species (RS) generation, with decreased skin antioxidant defenses. RS generation was positively correlated with skin thickness, wrinkles and PC levels. Once incorporated to skin, TFA make it more susceptible to developing UVR-induced disorders.

  10. Effects of propoxur on male fertility in wistar rat exposed neonatally

    Directory of Open Access Journals (Sweden)

    Augustave Kenfack

    2014-08-01

    Full Text Available Background: Propoxur is a carbamate pesticide widely used in crop and foodstuff protection. They are known to cause a wide variety of symptoms in animals. Methods: Twenty four young male rats were exposed to 0.00, 1.73, 2.60 and 5.20 mg/kg body weight through oral intubation for 90 days. Results: The testis weight increased significantly (P 0.05 but the percentage of sperm motility decreased significantly (P 0.05 change was observed between the control and treated males for the litter size, viability rate and sex-ratio. Conclusions: Despite the impairment of seminal epithelia and sperm characteristics, male rats orally exposed to the studied doses of propoxur maintained their fertility at the 90th day of treatment. [Int J Reprod Contracept Obstet Gynecol 2014; 3(4.000: 898-902

  11. BIOCHEMICAL AND HISTOPATHOLOGICAL EFFECTS OF MOBILE PHONE EXPOSURE ON RAT HEPATOCYTES AND BRAIN

    Directory of Open Access Journals (Sweden)

    Jovica Jovanović

    2010-03-01

    Full Text Available Microwave radiation MWR is widespread in human environment. The most frequent sources of MWR are mobile phones and cell towers. The effects of MWR are still unknown and there are insufficient data about long-term MWR effects on hepatocytes and brain structures.The aim of this paper was to investigate the biological effects of mobile phone microwave radiation on the brain and liver of experimental animals and to determine the increase in oxidative stress as a possible pathogenetic mechanism for harmful effects of long-term exposure.Wistar rats, 3 months old, were divided into two groups: I-rats constantly exposed to MWR (3 female and 2 male and II-control animals without near source of electromagnetic field (EMF (3 female and 2 male. The microwave radiation was produced by a mobile test phone (model NOKIA 3110; Nokia Mobile Phones Ltd. connected to a Communication Test Set (model 4202S; Wavetek, Germany. A 900 MHz electromagnetic near-field signal for GSM (Global System for Mobile communication at 900 MHz, continuous wave, analog phone system was used. The whole-body specific energy absorption (SAR rate was estimated as 0.025-0.05 W/kg (E=9.8-18.3 V/m, B=4.8-8.6 µT. Rats were sacrificed after 3 months of MWR exposure. The liver and brain were fixed in 10% formaldehyde and paraffin sections were stained by HE. The biochemical analyses comprised the determination of serum activity of AST (Aspartate aminotransferase, ALT (Alanine transaminase, GGT (Gamma-glutamyl transpeptidase and LDH (Lactate dehydrogenase, as well as determination of serum concentration of sodium, potassium and chloride. Lipid peroxidation was determined by measuring the quantity of malondialdehyde (MDA.Slightly increased number of micronuclei and discrete perivenular fatty changes were only histopathological findings in the liver of exposed rats. The discrete reduction of gray matter and reduced size and number of dendritic spines of Purkinje cells in cerebellum were notified

  12. 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.

  13. Metaplastic changes of nasal respiratory epithelium in rats exposed to hexamethylphosphoramide (HMPA) by inhalation.

    OpenAIRE

    Lee, K. P.; Trochimowicz, H. J.

    1982-01-01

    Rats exposed by inhalation to hexamethylphosphoramide (HMPA) at concentrations of 50, 100, 400, and 4000 parts per billion (ppb) for 6-24 months revealed nasal tumors and squamous metaplasia with inflammation in the nasal epithelium, but no changes were observed at 10 ppb. The ciliated cells were most susceptible to HMPA, showing degenerative changes, with abnormal cilia and extensive deciliation. The desquamated nasal epithelium was repaired initially by undifferentiated mucus or microvillou...

  14. Chinese green tea ameliorates lung injury in cigarette smoke-exposed rats

    OpenAIRE

    Koo, MWL; Ip, MSM; Man, RYK; Mak, JCW; Chan, KH; Ho, SP; Yeung, SC; So, WHL; Cho, CH; Lam, WK

    2009-01-01

    Background: Epigallocatechin-3-gallate (EGCG), which has been shown to have potent antioxidant effect, comprises 80% of catechins in Chinese green tea. This study was to investigate whether cigarette smoke (CS) exposure would induce lung morphological changes and oxidative stress in the CS-exposed rat model, and whether Chinese green tea (Lung Chen tea with EGCG as its main active ingredient) consumption would alter oxidative stress in sera and lung leading to protection of CS-induced lung da...

  15. Endocrine disrupting effects in rats perinatally exposed to a dietary relevant mixture of phytoestrogens

    DEFF Research Database (Denmark)

    Boberg, Julie; Mandrup, Karen; Jacobsen, Pernille Rosenskjold

    2013-01-01

    Dietary phytoestrogens may prevent certain human diseases, but endocrine activity has been reported in animal studies. Sprague-Dawley rats were exposed perinatally to a 1-, 10- or 100-fold “high human dietary intake” mixture of 12 phytoestrogens consisting of mainly the lignan secoisolarici resin....... Further studies are warranted to increase the knowledge upon which risk assessment on dietary phytoestrogen exposure during pregnancy and infancy is based....

  16. Ultrastructural changes, increased oxidative stress, inflammation, and altered cardiac hypertrophic gene expressions in heart tissues of rats exposed to incense smoke.

    Science.gov (United States)

    Al-Attas, Omar S; Hussain, Tajamul; Ahmed, Mukhtar; Al-Daghri, Nasser; Mohammed, Arif A; De Rosas, Edgard; Gambhir, Dikshit; Sumague, Terrance S

    2015-07-01

    Incense smoke exposure has recently been linked to cardiovascular disease risk, heart rate variability, and endothelial dysfunction. To test the possible underlying mechanisms, oxidative stress, and inflammatory markers, gene expressions of cardiac hypertrophic and xenobiotic-metabolizing enzymes and ultrastructural changes were measured, respectively, using standard, ELISA-based, real-time PCR, and transmission electron microscope procedures in heart tissues of Wistar rats after chronically exposing to Arabian incense. Malondialdehyde, tumor necrosis alpha (TNF)-α, and IL-4 levels were significantly increased, while catalase and glutathione levels were significantly declined in incense smoke-exposed rats. Incense smoke exposure also resulted in a significant increase in atrial natriuretic peptide, brain natriuretic peptide, β-myosin heavy chain, CYP1A1 and CYP1A2 messenger RNAs (mRNAs). Rats exposed to incense smoke displayed marked ultrastructural changes in heart muscle with distinct cardiac hypertrophy, which correlated with the augmented hypertrophic gene expression as well as markers of cardiac damage including creatine kinase-myocardial bound (CK-MB) and lactate dehydrogenase (LDH). Increased oxidative stress, inflammation, altered cardiac hypertrophic gene expression, tissue damage, and architectural changes in the heart may collectively contribute to increased cardiovascular disease risk in individuals exposed to incense smoke. Increased gene expressions of CYP1A1 and CYP1A2 may be instrumental in the incense smoke-induced oxidative stress and inflammation. Thus, incense smoke can be considered as a potential environmental pollutant and its long-term exposure may negatively impact human health.

  17. 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.

  18. Development of motor coordination and cerebellar structure in male and female rat neonates exposed to hypergravity

    Science.gov (United States)

    Nguon, K.; Ladd, B.; Baxter, M. G.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that the developing rat cerebellum is affected by exposure to hypergravity. In the present study, we explored the hypothesis that the changes in cerebellar structure in hypergravity-exposed rat neonates may affect their motor coordination. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravitational loading. To test this hypothesis, we compared motor behavior, cerebellar structure, and protein expression in rat neonates exposed to 1.5 1.75G on a 24-ft centrifuge daily for 22.5 h starting on gestational day (G) 10, through birth on G22/G23 and through postnatal day (P) 21. Exposure to hypergravity impacted the neurodevelopmental process as indicated by: (1) impaired righting response on P3, more than doubling the righting time at 1.75G, and (2) delayed onset of the startle response by one day, from P9 in controls to P10 in hypergravity-exposed pups. Hypergravity exposure resulted in impaired motor functions as evidenced by performance on a rotarod on P21; the duration of the stay on the rotarod recorded for 1.75G pups of both sexes was one tenth that of the stationary control (SC) pups. These changes in motor behavior were associated with cerebellar changes: (1) cerebellar mass on P6 was decreased by 7.5% in 1.5G-exposed male pups, 27.5% in 1.75G-exposed male pups, 17.5% in 1.5G-exposed female pups, and 22.5% in 1.75G female pups and (2) changes in the expression of glial and neuronal proteins. The results of this study suggest that perinatal exposure to hypergravity affects cerebellar development as evidenced by decreased cerebellar mass and altered cerebellar protein expression; cerebellar changes observed in hypergravity-exposed rat neonates are associated with impaired motor behavior. Furthermore, the response to hypergravity appears to be different in male and female neonates. If one accepts that the hypergravity paradigm is a useful animal model with which to predict those biological processes

  19. Effect of honey on the reproductive system of male rat offspring exposed to prenatal restraint stress.

    Science.gov (United States)

    Haron, M N; Mohamed, M

    2016-06-01

    Exposure to prenatal stress is associated with impaired reproductive function in male rat offspring. Honey is traditionally used by the Malays for enhancement of fertility. The aim of this study was to determine the effect of honey on reproductive system of male rat offspring exposed to prenatal restraint stress. Dams were divided into four groups (n = 10/group): control, honey, stress and honey + stress groups. Dams from honey and honey + stress groups received oral honey (1.2 g kg(-1) body weight) daily from day 1 of pregnancy, meanwhile dams from stress and honey + stress groups were subjected to restraint stress (three times per day) from day 11 of pregnancy until delivery. At 10 weeks old, each male rat offspring was mated with a regular oestrus cycle female. Male sexual behaviour and reproductive performance were evaluated. Then, male rats were euthanised for assessment on reproductive parameters. Honey supplementation during prenatal restraint stress significantly increased testis and epididymis weights as well as improved the percentages of abnormal spermatozoa and sperm motility in male rat offspring. In conclusion, this study might suggest that supplementation of honey during pregnancy seems to reduce the adverse effects of restraint stress on reproductive organs weight and sperm parameters in male rat offspring.

  20. Trans-resveratrol reduces cardiac oxidative stress in rats exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Melina Hauck

    2015-07-01

    Full Text Available Differences between reactive oxygen species and antioxidant defense system unbalance the redox status. The exposure to cigarette smoke can increase this imbalance. Trans-resveratrol is a polyphenol with great antioxidant action that reduces the oxidative stress. This study investigated the effect of the trans-resveratrol supplementation on the cardiac oxidative stress in rats exposed to cigarette smoke. Male Wistar rats were randomized into four groups: Control Group (CG, Exposure to Smoke Group (ESG, Antioxidant Group (AG and Exposure to Smoke plus Antioxidant Group (ESAG. Animals were exposed to cigarette smoke and supplemented with trans-resveratrol (6.0 mg kg-1 for two months. The lipid peroxidation (TBARS and the enzymatic activity of catalase (CAT were measured in the cardiac muscle. The ESG presented the highest lipid peroxidation level compared with CG (p < 0.001, AG (p < 0.001 and ESAG (p < 0.006. The CAT activity was higher in the AG (p < 0.001 and ESAG (p < 0.001 compared with CG. The ESG presented lower CAT activity compared with the ESAG (p < 0.001. The supplementation of Trans-resveratrol attenuated the cardiac oxidative stress and increased the activity of catalase. Our findings evidenced the cardioprotective effect of trans-resveratrol in rats exposed to cigarette smoke.

  1. Changes in operant behavior of rats exposed to lead at the accepted no-effect level.

    Science.gov (United States)

    Gross-Selbeck, E; Gross-Selbeck, M

    1981-11-01

    After weaning, male and female Wistar rats were fed a daily diet containing 1 g lead acetate/kg food until a level of about 20 micrograms/100 mL blood was obtained. The male rats were subjected to the different behavioral tests, whereas the females were mated to untreated males and further exposed until weaning of the offspring. Behavioral testing of the male offspring was performed between 3 and 4 months of age. General behavior of both groups was tested in the open-field task including locomotion, local movements, and emotionality. The conditioned instrumental behavior was tested in the Skinner box from simple to more complex programs. The blood-lead level was measured by flameless atomic absorption spectrometry. No behavioral changes became apparent in the open-field task and in the preliminary operant training. In the more complex programs (DRH = Differential Reinforcement of High Rates), the rats exposed to lead after weaning showed slight changes of DRH performance. By contrast, in pre- and neonatally exposed animals, DRH performance was significantly increased, although blood-lead levels had returned to normal at the time of testing. A comparison of lead effects in animals to possible effects in man is discussed in this paper, and it is concluded that lead exposure to man at doses which presently are suggested to be innocuous may result in subclinical functional changes of the central nervous system.

  2. Oxidative damage to rat brain in iron and copper overloads.

    Science.gov (United States)

    Musacco-Sebio, Rosario; Ferrarotti, Nidia; Saporito-Magriñá, Christian; Semprine, Jimena; Fuda, Julián; Torti, Horacio; Boveris, Alberto; Repetto, Marisa G

    2014-08-01

    This study reports on the acute brain toxicity of Fe and Cu in male Sprague-Dawley rats (200 g) that received 0 to 60 mg kg(-1) (ip) FeCl2 or CuSO4. Brain metal contents and time-responses were determined for rat survival, in situ brain chemiluminescence and phospholipid and protein oxidation products. Metal doses hyperbolically defined brain metal content. Rat survival was 91% and 60% after Fe and Cu overloads. Brain metal content increased from 35 to 114 μg of Fe per g and from 3.6 to 34 μg of Cu per g. Brain chemiluminescence (10 cps cm(-2)) increased 3 and 2 times after Fe and Cu overloads, with half maximal responses (C50) of 38 μg of Fe per g of brain and 15 μg of Cu per g of brain, and with half time responses (t1/2) of 12 h for Fe and 20 h for Cu. Phospholipid peroxidation increased by 56% and 31% with C50 of 40 μg of Fe per g and 20 μg of Cu per g and with t1/2 of 9 h and 14 h. Protein oxidation increased by 45% for Fe with a C50 of 40 μg of Fe per g and 18% for Cu with a C50 of 10 μg of Cu per g and a t1/2 of 12 h for both metals. Fe and Cu brain toxicities are likely mediated by Haber-Weiss type HO˙ formation with subsequent oxidative damage.

  3. Systemic physiology and neuroapoptotic profiles in young and adult rats exposed to surgery

    DEFF Research Database (Denmark)

    Ibrahim, Rami Mossad; Krammer, Caspar Weel; Hansen, Tom Giedsing

    2015-01-01

    BACKGROUND: Experimental evidence indicates that general anaesthetics can induce apoptotic neurodegeneration in the developing brain. The majority of these studies have been performed in the absence of surgery and it currently remains unclear how the presence of surgical stimuli would influence...... in experimental groups receiving dexmedetomidine, while propofol administration was associated with increased systemic lactate levels and metabolic acidosis. A substantial difference in anaesthesia/surgery-induced neuroapoptosis was found between young and adult rats in several brain regions. Combination...... and adult spontaneously breathing rats undergoing surgery. These observations further enlighten the need for detailed physiological monitoring under these experimental conditions. Although some statistically significant differences in activated caspase-3 profiles were detected between experimental groups...

  4. Diazinon concentrations and blood cholinesterase activities in rats exposed to diazinon.

    Science.gov (United States)

    Tomokuni, K; Hasegawa, T

    1985-04-01

    The tissue distribution of diazinon and the inhibition of blood cholinesterase (ChE) activity were investigated in male rats which received a single intraperitoneal (i.p.) dose of diazinon (100 mg/kg body wt) in olive oil. Diazinon concentration in the blood reached a maximum 1-2 h after dosing. Comparing the distribution of diazinon among liver, kidney and brain in treated rats, the diazinon residue was much greater in the kidney than in other organs, being 500 times that in the liver and 11 times that in the brain at 8 h after dosing. Erythrocyte and plasma ChE activities were inhibited rapidly, but ChE inhibition was greater in the erythrocytes than in plasma.

  5. Effects of taurine on cardiovascular and autonomic nervous functions in cold exposed rats.

    Science.gov (United States)

    Kuwahara, Masayoshi; Kawaguchi, Tomohiro; Ito, Koichi; Tsubone, Hirokazu

    2009-01-01

    Exposure to cold temperature might affect on cardiovascular and autonomic nervous function. Although there are a lot of studies on physiological and pathophysiological responses of taurine, it was poorly understood the effects of taurine on cardiovascular and autonomic nervous function during cold circumstances. Therefore, the purpose of this study was to clarify the possible role of taurine on cardiovascular and autonomic nervous function in rats exposed to cold temperature. For this purpose, heart rate, blood pressure and locomotive activity were recorded from conscious and unrestrained rats using a telemetry system. Moreover, the autonomic nervous function was investigated by power spectral analysis of heart rate variability. After the recovery period of implantation of transmitter, 1% taurine was supplied during experimental period ad libitum. After the 7 days control period, both taurine administrated and control groups of rats were exposed a cold temperature. There were no differences in heart rate, blood pressure and locomotive activity between taurine and control groups before cold exposure. However, parasympathetic nervous function was somewhat predominant in taurine group. Heart rate and blood pressure in both groups increased greatly by cold exposure. Heart rate in taurine group was much higher than that in control group. LF and HF powers were decreased by cold exposure in both groups. Although no differences were observed in LF, decrease of HF in taurine group was greater than that in control group. These results suggested that taurine might provide some reservoir for cardiovascular and autonomic nervous function to cold stress in rats.

  6. Altered spontaneous contractions of the ileum by anesthetic agents in rats exposed to peritonitis

    Institute of Scientific and Technical Information of China (English)

    Cengiz Aydin; Ihsan Bagcivan; Sinan Gursoy; Ahmet Altun; Omer Topcu; Ayhan Koyuncu

    2009-01-01

    AIM: To investigate in vitro effects of propofol, midazolam and dexmedetomidine, which are commonly used anaesthesic or sedatives, on spontaneous contractions of the ileum both in normal rats and those exposed to hyperdynamic peritonitis. METHODS: Spontaneous contractions of isolated ileum muscle segments from sham operated rats and those exposed to peritonitis, were studied in vitro. The amplitude and the frequency of spontaneous contractions of ileum muscle segments were studied after adding dexmetetomidine, propofol, and midazolam to the organ bath in a cumulative manner. Spontaneous contractions in ileum smooth muscle segments were decreased significantly in the peritonitis group compared to the control group ( P<0.05). Dexmedetomidine significantly increased the amplitude and peritonitis groups. The frequency of spontaneous contractions were significantly decreased by propofol Dexmedetomidine and midazolam did not cause significant changes in the number of spontaneous contractions in both control and the peritonitis groups ( P>0.05). CONCLUSION: Propofol, midazolam and dexmedetomidine have various in vitro effects on spontaneous contractions of the rat ileum. While dexmedetomidine augments the spontaneous contraction of the rat ileum, propofol attenuates it. However, the effects of these compounds were parallel in both control and peritonitis groups.

  7. Demonstration of endogenous imipramine like material in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Rehavi, M.; Ventura, I.; Sarne, Y.

    1985-02-18

    The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits (/sup 3/H) imipramine specific binding and mimics the inhibitory effect of imipramine on (/sup 3/H) serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits (/sup 3/H) imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum.

  8. Choline supplementation mitigates trace, but not delay, eyeblink conditioning deficits in rats exposed to alcohol during development.

    Science.gov (United States)

    Thomas, Jennifer D; Tran, Tuan D

    2012-03-01

    Children exposed to alcohol prenatally suffer from a range of physical, neuropathological, and behavioral alterations, referred to as fetal alcohol spectrum disorders (FASD). Both the cerebellum and hippocampus are affected by alcohol exposure during development, which may contribute to behavioral and cognitive deficits observed in children with FASD. Despite the known neuropathology associated with prenatal alcohol exposure, many pregnant women continue to drink (heavy drinkers, in particular), creating a need to identify effective treatments for their children who are adversely affected by alcohol. We previously reported that choline supplementation can mitigate alcohol's effects on cognitive development, specifically on tasks which depend on the functional integrity of the hippocampus. The present study examined whether choline supplementation could differentially mitigate alcohol's effects on trace eyeblink classical conditioning (ECC, a hippocampal-dependent task) and delay ECC (a cerebellar-dependent task). Long-Evans rats were exposed to 5.25 g/kg/day alcohol via gastric intubation from postnatal days (PD) 4-9, a period of brain development equivalent to late gestation in humans. A sham-intubated control group was included. From PD 10-30, subjects received subcutaneous injections of 100 mg/kg choline chloride or vehicle. Beginning on PD 32-34, subjects were trained on either delay or trace eyeblink conditioning. Performance of subjects exposed to alcohol was significantly impaired on both tasks, as indicated by significant reductions in percentage and amplitude of conditioned eyeblink responses, an effect that was attenuated by choline supplementation on the trace, but not delay conditioning task. Indeed, alcohol-exposed subjects treated with choline performed at control levels on the trace eyeblink conditioning task. There were no significant main or interactive effects of sex. These data indicate that choline supplementation can significantly reduce the

  9. Adiponectin alleviates contractile dysfunction of genioglossus in rats exposed to chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    WANG Wen-jing; LU Gan; DING Ning; HUANG Han-peng; DING Wen-xiao; ZHANG Xi-long

    2013-01-01

    Background Genioglossal dysfuntion takes an important role in pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) in which chronic intermittent hypoxia (CIH) is the major pathological origin.Recent studies have suggested genioglossal injury induced by CIH might be improved by adiponectin.The aim of this study was to investigate the effects of adiponectin on genioglossus contractile properties in rats exposed to CIH.Methods Thirty-nine healthy male Wistar rats were randomly divided into three groups:normal control (NC),CIH and adiponectin supplement (CIH+Ad) with 13 rats in each.Rats in NC were kept breathing normal air,while rats in CIH and CIH+Ad experienced the same CIH environment eight hours per day for 35 successive days.Rats in CIH+Ad were given intravenous adiponectin of 10 μg twice a week for 30 successive days.Rats in the NC and CIH were injected with normal saline as a control.After 35 days' CIH exposure,the levels of serum adiponectin and genioglossus contractile properties were compared.Results Serum adiponectin level was significantly lower in CIH than in NC (1210 ng/ml vs.2236 ng/ml).Serum adiponectin level in CIH+Ad (1844 ng/ml) was significantly higher than CIH but lower than NC.Twitch tension,time to peak tension,half relaxation time and tetanic tension were significantly lower in CIH than NC and improved in CIH+Ad.All mean tetanic fatigue indices decreased more rapidly in the first 20 seconds than during the subsequent 100 seconds.Tetanic fatigue indices in NC and CIH+Ad were significantly higher compared to CIH.Conclusions CIH could lead to hypoadiponectinaemia,impaired genioglossus contractile properties and decreased fatigue resistance in rats.Such changes could be partially offset by supplementation of adiponectin.

  10. 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

  11. 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.

  12. Primary Blast Traumatic Brain Injury in the Rat: Relating Diffusion Tensor Imaging and Behavior

    Directory of Open Access Journals (Sweden)

    Matthew D Budde

    2013-10-01

    Full Text Available The incidence of traumatic brain injury (TBI among military personnel is at its highest point in U.S. history. Experimental animal models of blast have provided a wealth of insight into blast injury. The mechanisms of neurotrauma caused by blast, however, are still under debate. Specifically, it is unclear whether the blast shockwave in the absence of head motion is sufficient to induce brain trauma. In this study, the consequences of blast injury were investigated in a rat model of primary blast TBI. Animals were exposed to blast shockwaves with peak overpressures of either 100 or 450 kPa and subsequently underwent a battery of behavioral tests. Diffusion tensor imaging (DTI, a promising method to detect blast injury in humans, was performed on fixed brains to detect and visualize the spatial dependence of blast injury. Blast TBI caused significant deficits in memory function as evidenced by the Morris Water Maze, but limited emotional deficits as evidenced by the Open Field Test and Elevated Plus Maze. Fractional anisotropy (FA, a metric derived from DTI, revealed significant brain abnormalities in blast-exposed animals. A significant relationship between memory deficits and brain microstructure was evident in the hippocampus, consistent with its role in memory function. The results provide fundamental insight into the neurological consequences of blast TBI, including the evolution of injury during the sub-acute phase and the spatially dependent pattern of injury. The relationship between memory dysfunction and microstructural brain abnormalities may provide insight into the persistent cognitive difficulties experienced by soldiers exposed to blast neurotrauma and may be important to guide therapeutic and rehabilitative efforts.

  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. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring.

    Science.gov (United States)

    Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Christiansen, Sofie; Hass, Ulla

    2013-09-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T₄) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gestation and lactation. Total T₄ serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T₄ in dams, but no significant effects on T₄ levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure through maternal milk, a second study using direct per oral pup exposure from postnatal day 3-16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T₄ reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing that in rats lactational transfer of triclosan seems limited. Since an optimal study design for testing potential developmental neurotoxicants in rats, should include exposure during both the pre- and postnatal periods of brain development, we suggest that in the case of triclosan, direct dosing of pups may be the best way to obtain that goal.

  15. ischemic brain injury in neonatal rats

    African Journals Online (AJOL)

    Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants,. Inflammatory markers .... were then moved back to their respective dams and immediately ..... various pro-inflammatory cytokines is stimulated.

  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. Modulation of mammary gland development in prepubertal male rats exposed to genistein and methoxychlor.

    Science.gov (United States)

    You, Li; Sar, Madhabananda; Bartolucci, Erika J; McIntyre, Barry S; Sriperumbudur, Rajagopal

    2002-04-01

    The estrogenic isoflavone genistein is a common dietary component that has been shown to affect reproductive development in experimental animals at high doses. The objective of the present study was to examine interactions of genistein and the hormonally active pesticide methoxychlor on mammary gland development in juvenile rats. Timed-pregnant Sprague-Dawley rats were fed a soy- and alfalfa-free diet containing different combinations of genistein (300 and 800 ppm) and methoxychlor (800 ppm). Rats were fed these diets starting on gestation day (GD)1 and continuing through pregnancy and lactation until postnatal day (PND) 22, when the pups were killed. Inguinal mammary glands from both female and male pups were processed as whole-mount preparations for morphometric analysis. The total glandular area and the numbers of branch points, lateral buds, and terminal end buds in the male rats were found to be significantly greater in the groups exposed to methoxychlor than those exposed to genistein only. These effects were not observed in the female rats. In the male rats, methoxychlor had the most prominent effect on elongating the glandular ducts, while genistein enhanced the ductile branching. The 2 compounds in combination promoted the development of alveolar-lobular structure, an effect not observed with either compound alone. Immunostaining for proliferating cell nuclear antigen revealed a high percentage of immunopositive cells in the mammary epithelia of the males exposed to methoxychlor and genistein (800 ppm) compared to the controls. While no significant changes in serum levels of mammotrophic hormones were detected, increased immunostaining for insulin-like growth factor-1 receptor, estrogen receptor alpha, and progesterone receptor in the genistein + methoxychlor group suggested that local factors involved in regulating mammary growth may have played a role in propagating the endocrine effects of these two compounds. These results indicated that the mammary

  18. Influence of electromagnetic field (1800 MHz on lipid peroxidation in brain, blood, liver and kidney in rats

    Directory of Open Access Journals (Sweden)

    Paweł Bodera

    2015-08-01

    Full Text Available Objectives: The aim of this study is the evaluation of the influence of repeated (5 times for 15 min exposure to electromagnetic field (EMF of 1800 MHz frequency on tissue lipid peroxidation (LPO both in normal and inflammatory state, combined with analgesic treatment. Material and Methods: The concentration of malondialdehyde (MDA as the end-product of the lipid peroxidation (LPO was estimated in blood, liver, kidneys, and brain of Wistar rats, both healthy and those with complete Freund’s adjuvant (CFA-induced persistent paw inflammation. Results: The slightly elevated levels of the MDA in blood, kidney, and brain were observed among healthy rats in electromagnetic field (EMF-exposed groups, treated with tramadol (TRAM/EMF and exposed to the EMF. The malondialdehyde remained at the same level in the liver in all investigated groups: the control group (CON, the exposed group (EMF, treated with tramadol (TRAM as well as exposed to and treated with tramadol (TRAM/EMF. In the group of animals treated with the complete Freund’s adjuvant (CFA we also observed slightly increased values of the MDA in the case of the control group (CON and the exposed groups (EMF and TRAM/EMF. The MDA values concerning kidneys remained at the same levels in the control, exposed, and not-exposed group treated with tramadol. Results for healthy rats and animals with inflammation did not differ significantly. Conclusions: The electromagnetic field exposure (EMF, applied in the repeated manner together with opioid drug tramadol (TRAM, slightly enhanced lipid peroxidation level in brain, blood, and kidneys.

  19. Protective Effects of Hydroalcoholic Extract of Nasturtium officinale on Rat Blood Cells Exposed to Arsenic

    Directory of Open Access Journals (Sweden)

    Felor Zargari

    2015-06-01

    Full Text Available Background: Arsenic is one of the most toxic metalloids. Anemia and leukopenia are common results of poisoning with arsenic, which may happen due to a direct hemolytic or cytotoxic effect on blood cells. The aim of this study was to examine the effects of hydroalcoholic extract of Nasturtium officinale on blood cells and antioxidant enzymes in rats exposed to sodium (metaarsenite. Methods: 32 Male Sprague Dawley rats were randomly divided into four groups; Group I (normal healthy rats, Group II (treated with 5.5mg/kg of body weight of NaAsO2, Group III (treated with 500mg/kg of body weight of hydro-alcoholic extract of N. officinale, and Group IV (treated with group II and III supplementations. Blood samples were collected and red blood cell, white blood cell, hematocrit, hemoglobin, platelet, total protein and albumin levels and total antioxidant capacity were measured. Data was analyzed with Mann-Whitney U test. Results: WBC, RBC and Hct were decreased in the rats exposed to NaAsO2 (p<0.05. A significant increase was seen in RBC and Hct after treatment with the plant extract (p<0.05. There was no significant decrease in serum albumin and total protein in the groups exposed to NaAsO2 compared to the group I, but NaAsO2 decreased the total antioxidant capacity, significantly. Conclusion: The Nasturtium officinale extract have protective effect on arsenic-induced damage of blood cells.

  20. Ototoxicity in rats exposed to ethylbenzene and to two technical xylene vapours for 13 weeks

    Energy Technology Data Exchange (ETDEWEB)

    Gagnaire, Francois; Langlais, Cristina; Grossmann, Stephane; Wild, Pascal [Institut National de Recherche et de Securite, Departement Polluants et Sante, Vandoeuvre Cedex (France)

    2007-02-15

    Male Sprague-Dawley rats were exposed to ethylbenzene (200, 400, 600 and 800 ppm) and to two mixed xylenes (250, 500, 1,000 and 2,000 ppm total compounds) by inhalation, 6 h/day, 6 days/week for 13 weeks and sacrificed for morphological investigation 8 weeks after the end of exposure. Brainstem auditory-evoked responses were used to determine auditory thresholds at different frequencies. Ethylbenzene produced moderate to severe ototoxicity in rats exposed to the four concentrations studied. Increased thresholds were observed at 2, 4, 8 and 16 kHz in rats exposed to 400, 600 and 800 ppm ethylbenzene. Moderate to severe losses of outer hair cells of the organ of Corti occurred in animals exposed to the four concentrations studied. Exposure to both mixed xylenes produced ototoxicity characterized by increased auditory thresholds and losses of outer hair cells. Ototoxicity potentiation caused by ethylbenzene was observed. Depending on the mixed xylene studied and the area of the concentration-response curves taken into account, the concentrations of ethylbenzene in mixed xylenes necessary to cause a given ototoxicity were 1.7-2.8 times less than those of pure ethylbenzene. Given the high ototoxicity of ethylbenzene, the safety margin of less or equal to two (LOAEL/TWA) might be too small to protect workers from the potential risk of ototoxicity. Moreover, the enhanced ototoxicity of ethylbenzene and para-xylene observed in mixed xylenes should encourage the production of mixed xylenes with the lowest possible concentrations of ethylbenzene and para-xylene. (orig.)

  1. Bone growth and composition in weanling and mature rats exposed to chronic centrifugation

    Science.gov (United States)

    Keil, L. C.; Evans, J. W.

    1982-01-01

    The primary objective of the study is to determine the effect of continuous exposure to hypergravity on the development and composition of weight-bearing bone. The experimental results are seen to suggest that many, if not all, of the changes observed in bone growth and composition derive from the retarded growth rate of the centrifuged rats. Both centrifuged weanling and mature rats exhibit a significant reduction in femur length and mass. The changes in femur size are more apparent in the weanlings since they are exposed to hypergravity during their most rapid phase of skeletal development. In addition to a slower growth rate, the body mass of the mature and weanling animals is reduced even further by the depletion of body fat. The rapid loss of body fat observed in rats and mice during centrifugation, it is found, can produce a prompt and significant rise in relative femur mass after two weeks of exposure. After adaptation to centrifugation, however, relative femur mass is similar to that of controls at four and eight weeks. At 18 weeks, the centrifuged rats again exhibit an increase in relative femur mass. It is thought that this increase in relative femur mass may be generated by the difference in fat deposition between the 1-G controls and the high-G rats.

  2. Protective effects of captopril in diabetic rats exposed to ischemia/reperfusion renal injury.

    Science.gov (United States)

    Fouad, Amr A; Al-Mulhim, Abdulruhman S; Jresat, Iyad; Morsy, Mohamed A

    2013-02-01

    To investigate the potential protective effects of captopril, the angiotensin-converting enzyme inhibitor, in diabetic rats exposed to ischaemia/reperfusion (I/R) renal injury. Following successful induction of diabetes, captopril treatment (50 mg/kg/day, p.o.) was applied for 4 weeks, after which bilateral renal ischaemia was induced for 30 min followed by reperfusion for 24 h. Captopril significantly attenuated hyperglycaemia and hypoinsulinaemia in diabetic rats, and significantly reduced the elevations of serum creatinine and aldosterone levels, and renal malondialdehyde, tumour necrosis factor-α and nitric oxide (NO), and prevented the depletion of reduced glutathione caused by I/R in diabetic rats. Histopathological renal tissue damage induced by I/R in diabetic rats was ameliorated by captopril treatment. Immunohistochemical analysis revealed that captopril significantly attenuated the reduction of insulin content in pancreatic islet β-cells, and decreased the I/R-induced expression of inducible NO synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin and heme oxygenase-1 in the kidney tissue of diabetic rats. Captopril represents a potential candidate to reduce the risk of renal injury induced by ischaemia/reperfusion in type 2 diabetes. © 2012 The Authors. JPP © 2012. Royal Pharmaceutical Society.

  3. 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.

  4. The Impacts of Swimming Exercise on Hippocampal Expression of Neurotrophic Factors in Rats Exposed to Chronic Unpredictable Mild Stress

    Directory of Open Access Journals (Sweden)

    Pei Jiang

    2014-01-01

    Full Text Available Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were involved in the antidepressive effects of exercise, in this study, we assessed the effects of swimming exercise on hippocampal mRNA expression of several classes of the growth factors (BDNF, GDNF, NGF, NT-3, FGF2, VEGF, and IGF-1 and peptides (VGF and NPY in rats exposed to chronic unpredictable mild stress (CUMS. Our study demonstrated that the swimming training paradigm significantly induced the expression of BDNF and BDNF-regulated peptides (VGF and NPY and restored their stress-induced downregulation. Additionally, the exercise protocol also increased the antiapoptotic Bcl-xl expression and normalized the CUMS mediated induction of proapoptotic Bax mRNA level. Overall, our data suggest that swimming exercise has antidepressant effects, increasing the resistance to the neural damage caused by CUMS, and both BDNF and its downstream neurotrophic peptides may exert a major function in the exercise related adaptive processes to CUMS.

  5. Melatonin treatment reduces astrogliosis and apoptosis in rats with traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Abdolreza Babaee

    2015-09-01

    Full Text Available Objective(s:Melatonin is known as an anti-inflammatory agent, and it has been proven to exert neuroprotection through inhibition of cell death (apoptosis in several models of brain injury.Secondary injury following the primary traumatic brain injury (TBI results in glial cells activation, especially astrocytes. In fact, astrocyte activation causes the production of pro-inflammatory cytokines that may lead to secondary injury. Since most TBI research studies have focused on injured neurons and paid little attention to glial cells, the aim of current study was to investigate the effects of melatonin against astrocytes activation (astrogliosis, as well as inhibition of apoptosis in brain tissue of male rats after TBI. Materials and Methods: The animals were randomly allocated into five groups: sham group, TBI+ vehicle group (1% ethanol in saline and TBI+ melatonin groups (5 mg/kg, 10 mg/kg and 20 mg/kg. All rats were intubated and then exposed to diffuse TBI, except for the sham group. Immunohistochemical methods were conducted using glial fibrillary acidic protein (GFAP marker and TUNEL assay to evaluate astrocyte reactivity and cell death, respectively. Results: The results showed that based on the number of GFAP positive astrocytes in brain cortex, astrogliosis was reduced significantly (P

  6. Sex hormones and expression pattern of cytoskeletal proteins in the rat brain throughout pregnancy.

    Science.gov (United States)

    González-Arenas, Aliesha; Piña-Medina, Ana Gabriela; González-Flores, Oscar; Galván-Rosas, Agustín; Porfirio Gómora-Arrati; Camacho-Arroyo, Ignacio

    2014-01-01

    Pregnancy involves diverse changes in brain function that implicate a re-organization in neuronal cytoskeleton. In this physiological state, the brain is in contact with several hormones that it has never been exposed, as well as with very high levels of hormones that the brain has been in touch throughout life. Among the latter hormones are progesterone and estradiol which regulate several brain functions, including learning, memory, neuroprotection, and the display of sexual and maternal behavior. These functions involve changes in the structure and organization of neurons and glial cells that require the participation of cytoskeletal proteins whose expression and activity is regulated by estradiol and progesterone. We have found that the expression pattern of Microtubule Associated Protein 2, Tau, and Glial Fibrillary Acidic Protein changes in a tissue-specific manner in the brain of the rat throughout gestation and the start of lactation, suggesting that these proteins participate in the plastic changes observed in the brain during pregnancy. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.

  7. The time-dependent health and biochemical effects in rats exposed to stainless steel welding dust and its soluble form.

    Science.gov (United States)

    Halatek, Tadeusz; Stanislawska, Magdalena; Kaminska, Irena; Cieslak, Malgorzata; Swiercz, Radoslaw; Wasowicz, Wojciech

    2017-02-23

    Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese (Mn), and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. The principal objective of this study was to determine the dynamics of toxic effects of inhalation exposure to morphologically rated welding dust from stainless steel welding and its soluble form in TSE System with a dynamic airflow. We assessed the pulmonary toxicity of welding dust in Wistar rats exposed to 60.0 mg/m(3) of respirable-size welding dust (mean diameter 1.17 µm) for 2 weeks (6 h/day, 5 days/week); the aerosols were generated in the nose-only exposure chambers (NOEC). An additional aim included the study of the effect of betaine supplementation on oxidative deterioration in rat lung during 2 weeks of exposure to welding dust or water-soluble dust form. The animals were divided into eight groups (n = 8 per group): control, dust, betaine, betaine + dust, soluble-form dust, soluble-form dust + betaine, saline and saline + betaine groups. Rats were euthanized 1 or 2 weeks after the last exposure for assessment of pulmonary toxicity. Differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase-LDH) activities were determined in bronchoalveolar lavage (BAL) fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) concentrations were assessed in serum. The increase in polymorphonuclear (PMN) leukocytes in BAL fluid (a cytological index of inflammatory responses of the lung) is believed to reflect pulmonary toxicity of heavy metals. Biomarkers of toxicity assessed in bronchoalveolar fluids indicate that the level of the toxic effect depends mainly on the solubility of studied metal compounds; biomarkers that showed treatment effects included: total cell, neutrophil and lymphocyte counts, total protein concentrations, and cellular enzyme (lactate dehydrogenase) activity

  8. Early effects of lipopolysaccharide-induced inflammation on foetal brain development in rat

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    Cristina A Ghiani

    2011-11-01

    Full Text Available Studies in humans and animal models link maternal infection and imbalanced levels of inflammatory mediators in the foetal brain to the aetiology of neuropsychiatric disorders. In a number of animal models, it was shown that exposure to viral or bacterial agents during a period that corresponds to the second trimester in human gestation triggers brain and behavioural abnormalities in the offspring. However, little is known about the early cellular and molecular events elicited by inflammation in the foetal brain shortly after maternal infection has occurred. In this study, maternal infection was mimicked by two consecutive intraperitoneal injections of 200 μg of LPS (lipopolysaccharide/kg to timed-pregnant rats at GD15 (gestational day 15 and GD16. Increased thickness of the CP (cortical plate and hippocampus together with abnormal distribution of immature neuronal markers and decreased expression of markers for neural progenitors were observed in the LPS-exposed foetal forebrains at GD18. Such effects were accompanied by decreased levels of reelin and the radial glial marker GLAST (glial glutamate transporter, and elevated levels of pro-inflammatory cytokines in maternal serum and foetal forebrains. Foetal inflammation elicited by maternal injections of LPS has discrete detrimental effects on brain development. The early biochemical and morphological changes described in this work begin to explain the sequelae of early events that underlie the neurobehavioural deficits reported in humans and animals exposed to prenatal insults.

  9. Early Effects of Lipopolysaccharide-Induced Inflammation on Foetal Brain Development in Rat

    Directory of Open Access Journals (Sweden)

    Cristina A Ghiani

    2011-10-01

    Full Text Available Studies in humans and animal models link maternal infection and imbalanced levels of inflammatory mediators in the foetal brain to the aetiology of neuropsychiatric disorders. In a number of animal models, it was shown that exposure to viral or bacterial agents during a period that corresponds to the second trimester in human gestation triggers brain and behavioural abnormalities in the offspring. However, little is known about the early cellular and molecular events elicited by inflammation in the foetal brain shortly after maternal infection has occurred. In this study, maternal infection was mimicked by two consecutive intraperitoneal injections of 200 μg of LPS (lipopolysaccharide/kg to timed-pregnant rats at GD15 (gestational day 15 and GD16. Increased thickness of the CP (cortical plate and hippocampus together with abnormal distribution of immature neuronal markers and decreased expression of markers for neural progenitors were observed in the LPS-exposed foetal forebrains at GD18. Such effects were accompanied by decreased levels of reelin and the radial glial marker GLAST (glial glutamate transporter, and elevated levels of pro-inflammatory cytokines in maternal serum and foetal forebrains. Foetal inflammation elicited by maternal injections of LPS has discrete detrimental effects on brain development. The early biochemical and morphological changes described in this work begin to explain the sequelae of early events that underlie the neurobehavioural deficits reported in humans and animals exposed to prenatal insults.

  10. The effects of hyperbaric air and hyperbaric oxygen on blood-brain barrier integrity in rats.

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    Cevik, Nihal Gunes; Orhan, Nurcan; Yilmaz, Canan Ugur; Arican, Nadir; Ahishali, Bulent; Kucuk, Mutlu; Kaya, Mehmet; Toklu, Akin Savas

    2013-09-19

    Hyperbaric oxygen (HBO) treatment yields conflicting results on blood-brain barrier (BBB) integrity under various pathological conditions and the effects of HBO on healthy brain is poorly understood. In this experimental study, the effects of HBO on BBB integrity were investigated in comparison with hyperbaric air (HBA) in intact rats. Four sessions of HBA or HBO were applied to intact rats in 24h. BBB integrity was functionally and structurally evaluated by determining extravasation of Evans blue (EB) dye and horseradish peroxidase (HRP) tracers. In immunohistochemical evaluation, relative staining intensity for occludin, a tight junction (TJ) protein, and aquaporin 4 (AQP4), a water-channel protein, was detected in the barrier type of microvessels of brain by image analysis. BBB permeability to EB dye significantly increased in animals in HBO treatment group compared to those in HBA and control groups (p<0.05). The immunoreactivity of occludin, a tight junction protein, remained essentially unaltered in capillaries of hippocampus in all groups. In animals exposed to HBO, AQP4 immunoreactivity significantly increased in parietal cortex compared to those in HBA and control groups (p<0.01). Ultrastructurally, frequent vesicles containing HRP reaction products were observed in capillary endothelial cells in cerebral cortex and hippocampus of rats subjected to both HBA and HBO. Our results indicate that the HBO administration to intact rats increased BBB permeability to both EB and HRP while HBA increased only HRP extravasation in these animals. The results of this study suggest that HBA also impairs the BBB integrity in intact rats as well as HBO.

  11. Maternal administration of flutamide during late gestation affects the brain and reproductive organs development in the rat male offspring.

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    Pallarés, M E; Adrover, E; Imsen, M; González, D; Fabre, B; Mesch, V; Baier, C J; Antonelli, M C

    2014-10-10

    We have previously demonstrated that male rats exposed to stress during the last week of gestation present age-specific impairments of brain development. Since the organization of the fetal developing brain is subject to androgen exposure and prenatal stress was reported to disrupt perinatal testosterone surges, the aim of this research was to explore whether abnormal androgen concentrations during late gestation affects the morphology of the prefrontal cortex (PFC), hippocampus (HPC) and ventral tegmental area (VTA), three major areas that were shown to be affected by prenatal stress in our previous studies. We administered 10-mg/kg/day of the androgen receptor antagonist flutamide (4'nitro-3'-trifluoromethylsobutyranilide) or vehicle injections to pregnant rats from days 15-21 of gestation. The antiandrogenic effects of flutamide were confirmed by the analysis of androgen-dependent developmental markers: flutamide-exposed rats showed reduced anogenital distance, delay in the completion of testis descent, hypospadias, cryptorchidism and atrophied seminal vesicles. Brain morphological studies revealed that prenatal flutamide decreased the number of MAP2 (a microtubule-associated protein type 2, present almost exclusively in dendrites) immunoreactive neuronal processes in all evaluated brain areas, both in prepubertal and adult offspring, suggesting that prenatal androgen disruption induces long-term reductions of the dendritic arborization of several brain structures, affecting the normal connectivity between areas. Moreover, the number of tyrosine hydroxylase (TH)-immunopositive neurons in the VTA of prepubertal offspring was reduced in flutamide rats but reach normal values at adulthood. Our results demonstrate that the effects of prenatal flutamide on the offspring brain morphology resemble several prenatal stress effects suggesting that the mechanism of action of prenatal stress might be related to the impairment of the organizational role of androgens on brain

  12. Nuclear phenotype evaluation in skeletal muscle from Wistar rats exposed to low-level lasers

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    Almeida, L. G.; Sergio, L. P. S.; Vicentini, S. C.; Mencalha, A. L.; Paoli, F.; Fonseca, A. S.

    2017-03-01

    Low-level laser therapy includes devices emitting red and near-infrared radiation with output power below 100 mW. These devices are successfully used for the treatment of injuries and to improve exercise performance based on their biomodulatory effect. Despite the wide use of clinical protocols based on these lasers, the laser-induced effects on DNA are still disputed. Thus, the objective of this study was to investigate chromatin organization, ploidy degrees, and DNA fragmentation in skeletal muscle tissue from Wistar rats exposed to low-level red and infrared lasers. Wistar rats were exposed to low-level red and infrared lasers (25, 50, and 100 J cm-2, 100 mW, continuous-wave emission mode) and, after 24h, samples of this tissue were withdrawn for the analysis of chromatin organization, ploidy degrees, and DNA fragmentation by Feulgen reaction detection of micronucleus, and apoptosis by TUNEL assay. Data obtained show that low-level red and infrared lasers alter geometric and densitometric parameters as well ploidy degree in muscle nuclei from Wistar rats, but do not induce DNA fragmentation, chromatin loss, and apoptosis at fluences taken out from clinical protocols.

  13. Plasma renin is increased in young rats exposed to lead in utero and during nursing

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    Victery, W.; Vander, A.J.; Schoeps, P.; Germain, C.

    1983-01-01

    Rats were exposed continuously to Pb in utero and after birth by giving their mothers, during pregnancy and lactation, drinking water containing 0, 5, 25, 100, or 500 ppm Pb (as Pb acetate); they were sacrificed at 1 month of age, at which time their mean blood Pb concentrations were, respectively, approximately 3, 9, 19, 30, and 70 ..mu..g/dl. All Pb-exposed groups sacrificed by decapitation had elevated mean plasma renin activities (PRA), relative to controls. Pentobarbital-anesthesia and laparotomy markedly increased PRA in the 0, 100, and 500 ppm groups, but the increase was significantly less in the 100 ppm group. Renal renin concentration was normal in the 5 and 25 ppm groups, but was significantly increased in the 100 and 500 ppm groups. The ratio of plasma angiotensin II to PRA was normal in the 100 ppm group but significantly reduced in the 500 ppm group. We conclude that exposure of rats to those generally present in human populations stimulates basal renin secretion in 1-month-old rats, but partially inhibits the response to renin-releasing stimuli. The highest dose reduces plasma angiotensin II at any given PRA. These results, taken with previous publications, emphasize that the effects of lead on plasma renin even within a single species are greatly affected by the timing of the exposure.

  14. Inhibition of HMGB1 Translocation by Green Tea Extract in Rats Exposed to Environmental Tobacco Smoke

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    Sirintip Chaichalotornkul

    2012-01-01

    Full Text Available Environmental tobacco smoke (ETS exposure is linked to carcinogenic, oxidative and inflammatory cellular reactions. Green tea polyphenol reportedly plays a role in the prevention of inflammation-related diseases. To evaluate the effects of green tea extract (GTE on cellular location of High Mobility Group Box-1 (HMGB1 protein, we studied the lung tissue in rats exposed to cigarette smoke (CS. Rats were divided into three groups; CS, CSG, and C, which were groups of CS-treated only, CS-treated with GTE dietary supplement, and the control, respectively. Our findings by immunocytochemistry showed that abundant HMGB1 translocated from the nucleus to the cytoplasm in the lung tissues of rats that were exposed to CS, whereas HMGB1 was localized to the nuclei of CSG and C group. For in vitro studies, cotinine stimulated the secretion of HMGB1 in a dose and time dependent manner and the HMGB1 level was suppressed by GTE in murine macrophage cell lines. Our results could suggest that GTE supplementation which could suppress HMGB1 may offer a beneficial effect against diseases.

  15. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

    Science.gov (United States)

    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  16. Changes in the function of the inhibitory neurotransmitter system in the rat brain following subchronic inhalation exposure to 1-bromopropane.

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    Ueno, Susumu; Yoshida, Yasuhiro; Fueta, Yukiko; Ishidao, Toru; Liu, Jiqin; Kunugita, Naoki; Yanagihara, Nobuyuki; Hori, Hajime

    2007-03-01

    1-Bromopropane (1-BP) has been widely used as a cleaning agent and a solvent in industries, but the central neurotoxicity of 1-BP remains to be clarified. In the present study, we investigated the effects of subchronic inhalation exposure to 1-BP vapor on the function of the inhibitory neurotransmitter system mediated by gamma-aminobutyric acid (GABA) in the rat brain. Male Wistar rats were exposed to 1-BP vapor for 12 weeks (6h/day, 5 days/week) at a concentration of 400 ppm, and, in order to investigate the expression and function of brain GABA type A (GABAA) receptors, total/messenger RNA was prepared from the neocortex, hippocampus, and cerebellum of the control and 1-BP-exposed rats. Moreover, hippocampal slices were prepared, and the population spike (PS) amplitude and the slope of the field excitatory postsynaptic potential (fEPSP) were investigated in the paired-pulse configuration of the extracellular recording technique. Using the Xenopus oocyte expression system, we compared GABA concentration-response curves obtained from oocytes injected with brain subregional mRNAs of control and 1-BP exposed rats, and observed no significant differences in apparent GABA affinity. On the other hand, paired-pulse inhibition of PS amplitude was significantly decreased in the hippocampal dentate gyrus (DG) by exposure to 1-BP, without any effect on the paired-pulse ratio of the fEPSP slopes, suggesting neuronal disinhibition in the DG. Moreover, RT-PCR analysis indicated decreased levels of GABAA receptor beta3 and delta subunit mRNAs in the hippocampus of 1-BP-exposed rats. These results demonstrate that subchronic inhalation exposure to 1-BP vapor reduces the function of the hippocampal GABAergic system, which could be due to changes in the expression and function of GABAA receptors, especially the delta subunit-containing GABAA receptors.

  17. Ethylene glycol ethers induce apoptosis and disturb glucose metabolism in the rat brain.

    Science.gov (United States)

    Pomierny, Bartosz; Krzyżanowska, Weronika; Niedzielska, Ewa; Broniowska, Żaneta; Budziszewska, Bogusława

    2016-02-01

    Ethylene glycol ethers (EGEs) are compounds widely used in industry and household products, but their potential, adverse effect on brain is poorly understood, so far. The aim of the present study was to determine whether 4-week administration of 2-buthoxyethanol (BE), 2-phenoxyethanol (PHE), and 2-ethoxyethanol (EE) induces apoptotic process in the rat hippocampus and frontal cortex, and whether their adverse effect on the brain cells can result from disturbances in the glucose metabolism. Experiments were conducted on 40 rats, exposed to BE, PHE, EE, saline or sunflower oil for 4 weeks. Markers of apoptosis and glucose metabolism were determined in frontal cortex and hippocampus by western blot, ELISA, and fluorescent-based assays. BE and PHE, but not EE, increased expression of the active form of caspase-3 in the examined brain regions. BE and PHE increased caspase-9 level in the cortex and PHE also in the hippocampus. BE and PHE increased the level of pro-apoptotic proteins (Bax, Bak) and/or reduced the concentration of anti-apoptotic proteins (Bcl-2, Bcl-xL); whereas, the effect of BE was observed mainly in the cortex and that of PHE in the hippocampus. It has also been found that PHE increased brain glucose level, and both BE and PHE elevated pyruvate and lactate concentration. It can be concluded that chronic treatment with BE and PHE induced mitochondrial pathway of apoptosis, and disturbed glucose metabolism in the rat brain. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Expression of neuropeptide Y in rat brain ischemia

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    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.

  19. Nerve growth factor receptor molecules in rat brain

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    Taniuchi, M.; Schweitzer, J.B.; Johnson, E.M. Jr.

    1986-03-01

    The authors have developed a method to immunoprecipitate rat nerve growth factor (NGF) receptor proteins and have applied the method to detect NGF receptor molecules in the rat brain. Crosslinking /sup 125/I-labeled NGF to either PC12 cells or cultured rat sympathetic neurons yielded two radiolabeled molecules (90 kDa and 220 kDa) that were immunoprecipitated by monoclonal antibody 192-IgG. Further, 192-IgG precipitated two radiolabeled proteins, with the expected sizes (80 kDa and 210 kDa) of noncrosslinked NGF receptor components, from among numerous surface-iodinated PC12 cell proteins. These results demonstrate the specific immunoprecipitation of NGF receptor molecules by 192-IgG. They applied the /sup 125/I-NGF crosslinking and 192-IgG-mediated immunoprecipitation procedures to plasma membrane preparations of rat brain: NGF receptor molecules of the same molecular masses as the peripheral receptor components were consistently detected in all regions and in preparations from whole brains. Removal of the peripheral sympathetic innervation of the brain did not eliminate these NGF receptor proteins, indicating that the receptor is endogenous to central nervous system tissues. They also observed retrograde transport of /sup 125/I-labeled 192-IgG from the parietal cortex to the nucleus basalis and from the hippocampus to the nucleus of the diagonal band of Broca and the medial septal nucleus. These findings demonstrate the presence in brain of NGF receptor molecules indistinguishable from those of the peripheral nervous system.

  20. Preserved modular network organization in the sedated rat brain.

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    Dany V D'Souza

    Full Text Available Translation of resting-state functional connectivity (FC magnetic resonance imaging (rs-fMRI applications from human to rodents has experienced growing interest, and bears a great potential in pre-clinical imaging as it enables assessing non-invasively the topological organization of complex FC networks (FCNs in rodent models under normal and various pathophysiological conditions. However, to date, little is known about the organizational architecture of FCNs in rodents in a mentally healthy state, although an understanding of the same is of paramount importance before investigating networks under compromised states. In this study, we characterized the properties of resting-state FCN in an extensive number of Sprague-Dawley rats (n = 40 under medetomidine sedation by evaluating its modular organization and centrality of brain regions and tested for reproducibility. Fully-connected large-scale complex networks of positively and negatively weighted connections were constructed based on Pearson partial correlation analysis between the time courses of 36 brain regions encompassing almost the entire brain. Applying recently proposed complex network analysis measures, we show that the rat FCN exhibits a modular architecture, comprising six modules with a high between subject reproducibility. In addition, we identified network hubs with strong connections to diverse brain regions. Overall our results obtained under a straight medetomidine protocol show for the first time that the community structure of the rat brain is preserved under pharmacologically induced sedation with a network modularity contrasting from the one reported for deep anesthesia but closely resembles the organization described for the rat in conscious state.

  1. [Neurotoxic effect of toluene on background of prenatal hypoxic brain damage to white rats].

    Science.gov (United States)

    Vokina, V A; Sosedova, L M; Rukavishnikov, V S; Iakimova, N L; Lizarev, A V

    2014-01-01

    Comparative study covered influence of toluene on behavioral parameters, cognitive abilities and brain bioelectric activity in white rats with normal embryonic development or with prenatal hypoxia. Prenatal hypoxia was simulated by subcutaneous injection of 50 mg/kg sodium nitrite into female white rats on day 13-14 of gestation. The offspring at the age of 2, 5-3 months was exposed to toluene (concentration of 560 mg/m3, 4 hours per day, 5 days per week, over 4 weeks). After the exposure, the animals were estimated for individual and intraspecific behaviour in "open fields and "resident-intruder" tests, for cognitive abilities in "radial maze" training, EEG with visual and auditory evoked potentials. Acute hypoxia at early stages of organogenesis appeared to be burdening factor and to influence consequences of toluene intoxication.

  2. Effect of 900 MHz radiofrequency radiation on oxidative stress in rat brain and serum.

    Science.gov (United States)

    Bilgici, Birsen; Akar, Aysegul; Avci, Bahattin; Tuncel, Ozgur Korhan

    2013-03-01

    The increasing use of mobile telephones raises the question of possible adverse effects of the electromagnetic fields (EMF) that these phones produce. In this study, we examined the oxidative stress in the brain tissue and serum of rats that resulted from exposure to a 900-MHz EMF at a whole body average specific absorption rate (SAR) of 1.08 W/kg for 1 h/day for 3 weeks. We also examined the antioxidant effect of garlic powder (500 mg/kg/day) given orally to EMF-exposed rats. We found that malondialdehyde (MDA) (p advanced oxidation protein product (AOPP) (p electromagnetic radiation (EMR) exposure and that garlic has a protective effect against this oxidative stress.

  3. Effect of glycolysis inhibition on mitochondrial function in rat brain.

    Science.gov (United States)

    Cano-Ramírez, D; Torres-Vargas, C E; Guerrero-Castillo, S; Uribe-Carvajal, S; Hernández-Pando, R; Pedraza-Chaverri, J; Orozco-Ibarra, M

    2012-05-01

    Inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase enhances the neural vulnerability to excitotoxicity both in vivo and in vitro through an unknown mechanism possibly related to mitochondrial failure. However, as the effect of glycolysis inhibition on mitochondrial function in brain has not been studied, the aim of the present work was to evaluate the effect of glycolysis inhibition induced by iodoacetate on mitochondrial function and oxidative stress in brain. Mitochondria were isolated from brain cortex, striatum and cerebellum of rats treated systemically with iodoacetate (25 mg/kg/day for 3 days). Oxygen consumption, ATP synthesis, transmembrane potential, reactive oxygen species production, lipoperoxidation, glutathione levels, and aconitase activity were assessed. Oxygen consumption and aconitase activity decreased in the brain cortex and striatum, showing that glycolysis inhibition did not trigger severe mitochondrial impairment, but a slight mitochondrial malfunction and oxidative stress were present.

  4. Effect of acute thioacetamide administration on rat brain phospholipid metabolism

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    Osada, J.; Aylagas, H.; Miro-Obradors, M.J.; Arce, C.; Palacios-Alaiz, E.; Cascales, M. (Tufs Univ., Boston, MA (USA))

    1990-09-01

    Brain phospholipid composition and the ({sup 32}P)orthophosphate incorporation into brain phospholipids of control and rats treated for 3 days with thioacetamide were studied. Brain phospholipid content, phosphatidylcholine, phosphatidylethanolamine, lysolecithin and phosphatidic acid did not show any significant change by the effect of thioacetamide. In contrast, thioacetamide induced a significant decrease in the levels of phosphatidylserine, sphingomyelin, phosphatidylinositol and diphosphatidylglycerol. After 75 minutes of intraperitoneal label injection, specific radioactivity of all the above phospholipids with the exception of phosphatidylethanolamine and phosphatidylcholine significantly increased. After 13 hours of isotope administration the specific radioactivity of almost all studied phospholipid classes was elevated, except for phosphatidic acid, the specific radioactivity of which did not change and for diphosphatidylglycerol which showed a decrease in specific radioactivity. These results suggest that under thioacetamide treatment brain phospholipids undergo metabolic transformations that may contribute to the hepatic encephalopathy induced by thioacetamide.

  5. Upregulation of NRG-1 and VAMP-1 in human brain aggregates exposed to clozapine.

    Science.gov (United States)

    Chana, Gursharan; Lucero, Ginger; Salaria, Shahid; Lozach, Jean; Du, Pinyi; Woelk, Christopher; Everall, Ian

    2009-09-01

    Growing genetic evidence has implicated a role for neuregulin-1 (NRG-1) in schizophrenia pathogenesis as well as alterations in SNAP receptor (SNARE) proteins at both gene and protein levels in post-mortem investigations. In relation to a potential therapeutic mechanism for atypical antipsychotic medications, clozapine has been shown to increase both NRG-1 levels and synaptic markers in rodents. As evidence continues to mount for a potential restoration in connectivity by antipsychotic medications being a mode of efficacy we chose to examine the effects of the atypical antipsychotic clozapine and the typical antipsychotic haloperidol on NRG-1 and SNARE protein transcripts in human brain aggregates exposed to plasma levels chronically for a period of three weeks. At the end of this exposure period we performed quantitative real-time PCR to investigate the mRNA levels of NRG-1, VAMP-1 and SNAP-25. Overall we found that clozapine had the ability to upregulate NRG-1 (+3.58 fold change) and VAMP-1 (+1.92) while SNAP-25 remained unchanged. Changes for haloperidol exposed aggregates were below our cut-off of +1.5. Overall the results of our investigation lend further support to atypical antipsychotic medications having the potential to increase levels of neurotrophic and synaptic markers such as NRG-1 and VAMP-1, the former being a strong candidate susceptibility gene for schizophrenia. In the absence of frank neuronal loss in schizophrenia, restoration of neuronal and synaptic functions by atypical antipsychotics in the brains of schizophrenics maybe a key mechanism of therapeutic efficacy by re-establishing normal connectivity and functioning.

  6. Screening for History of Traumatic Brain Injury Among Women Exposed to Intimate Partner Violence.

    Science.gov (United States)

    Goldin, Yelena; Haag, Halina L; Trott, Charlotte T

    2016-11-01

    Traumatic brain injury (TBI) is a common chronically debilitating consequence of intimate-partner violence (IPV). Diagnosis and effective treatment are precluded by poor detection and lack of uniform practice guidelines for TBI screening in IPV. Although there are several TBI-screening tools commonly used in clinical and research practices, their applicability to this unique and vulnerable population is unclear. In this review paper, we propose a theoretically based framework for screening for history of TBI in women exposed to IPV and apply it to investigate the applicability of TBI-screening instruments. The framework was developed by examining existing guidelines for working with IPV survivors and applied to evaluate the content of nine currently available TBI screening instruments to determine the extent to which each offers (1) events that can lead to TBI in an IPV situation; (2) safe (without increasing the risk of retaliation) endorsement of an event; and (3) ease of administration. Our evaluation of the currently available TBI-screening tools determined that no instrument met the proposed framework standards and only 2 (Brain Injury Screening Questionnaire and Ohio State University TBI Identification Method) came close, requiring only minor adjustments to meet the postulated criteria. We make specific content and interview-based recommendations for revising TBI screening instruments to minimize the weaknesses of currently available screening tools among women exposed to IPV and the knowledge gaps about TBI in this context. The proposed framework and recommendations are intended to guide future work in this area to enhance the capacity of TBI screening tools to safely detect TBI in this population. V. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  7. Noninvasive method to assess the electrical brain activity from rats

    Directory of Open Access Journals (Sweden)

    Rosana Ferrari

    2013-10-01

    Full Text Available This research presents a noninvasive method for the acquisition of brain electrical signal in rat. Was used an electroencephalography (EEG system developed for bovine and adapted to rats. The bipolar electrode system (needle electrodes was glued on the surface of the head of the animal without surgical procedures and the other electrode was glued to the tail, as ground. The EEG activity was sampled at 120Hz for an hour. The accuracy and precision of the EEG measurement was performed using Fourier analysis and signal energy. For this, the digital signal was divided into sections successive of 3 seconds and was decomposed into four frequency bands: delta (0.3 to 4Hz, theta (4-8Hz, alpha (8-12Hz and beta (12-30Hz and energy (µV² of the series of time filtered were calculated. The method allowed the acquisition of non-invasive electrical brain signals in conscious rats and their frequency patterns were in agreement with previous studies that used surgical procedures to acquire EEG in rats. This system showed accuracy and precision and will allow further studies on behavior and to investigate the action of drugs on the central nervous system in rats without surgical procedures.

  8. Responsiveness of hepatic and cerebral cytochrome P450 in rat offspring prenatally and lactationally exposed to a reconstituted PCB mixture.

    Science.gov (United States)

    Bonfanti, Patrizia; Comelli, Francesca; Assi, Laura; Casati, Lavinia; Colciago, Alessandra; Villa, Sara; Santagostino, Angela; Costa, Barbara; Colombo, Anita

    2014-08-01

    Perinatal polychlorinated biphenyl (PCB) exposures still remain a serious health concern because offspring receive PCB burden from mother during vulnerable processes of development. Since cytochrome P450 (CYP) represents a toxicological endpoint, in the present study, representing an extended investigation of a previous multitasked one, we explored the long-term responsiveness of CYP1A and CYP2B isoforms by Western blot analysis in liver and whole brain of lactating (PN12), weaning (PN21), and adult offspring (PN60) rats prenatally and lactationally exposed to a reconstituted PCB mixture (RM) of noncoplanar PCB138, 153, 180, and coplanar PCB126 congeners. We chose highly chlorinated PCBs instead of lower chlorinated one, because their recalcitrance to biotransformation makes easy their accumulation/persistence in tissues and breast milk. Dioxin-like congener PCB126 binding aryl hydrocarbon receptor (AHR) is responsible of many toxic effects. Pregnant Sprague-Dawley dams with high affinity AHR received subcutaneous injection of RM (10 mg/kg body weight) daily during gestation (days 15-19) and twice a week during breast-feeding. The results evidenced a transfer of PCBs to neonates through milk and a significant responsiveness of hepatic CYP in both mothers and offspring. In liver of exposed progeny, CYP isoforms exhibited a significant increment at PN12 (70% over control) and at PN21 (270% over control). Contrary to dams, in adult PCB offspring CYP levels showed a decline up to values similar to those of control. This transient developmental responsiveness of CYP isoforms in offspring liver reflects roughly the time course of hepatic PCB levels previously reported. Even if congeners were detected in brain, we failed in evidencing a responsiveness of CYP isoforms probably because of region-specific CYP expression in this organ. In conclusion, induction of offspring hepatic CYP is index of liver PCB burden, and despite the insensitivity of whole brain CYP we cannot

  9. Significant long-term, but not short-term, hippocampal-dependent memory impairment in adult rats exposed to alcohol in early postnatal life.

    Science.gov (United States)

    Goodfellow, Molly J; Lindquist, Derick H

    2014-09-01

    In rodents, ethanol exposure in early postnatal life is known to induce structural and functional impairments throughout the brain, including the hippocampus. Herein, rat pups were administered one of three ethanol doses over postnatal days (PD) 4-9, a period of brain development comparable to the third trimester of human pregnancy. As adults, control and ethanol rats were trained and tested in a variant of hippocampal-dependent one-trial context fear conditioning. In Experiment 1, subjects were placed into a novel context and presented with an immediate footshock (i.e., within ∼8 sec). When re-exposed to the same context 24 hr later low levels of conditioned freezing were observed. Context pre-exposure 24 hr prior to the immediate shock reversed the deficit in sham-intubated and unintubated control rats, enhancing freezing behavior during the context retention test. Even with context pre-exposure, however, significant dose-dependent reductions in contextual freezing were seen in ethanol rats. In Experiment 2, the interval between context pre-exposure and the immediate shock was shortened to 2 hr, in addition to the standard 24 hr. Ethanol rats trained with the 2 hr, but not 24 hr, interval displayed retention test freezing levels roughly equal to controls. Results suggest the ethanol rats can encode a short-term context memory and associate it with the aversive footshock 2 hr later. In the 24 hr ethanol rats the short-term context memory is poorly transferred or consolidated into long-term memory, we propose, impeding the memory's subsequent retrieval and association with shock.

  10. Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

    Science.gov (United States)

    Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

    2014-01-01

    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

  11. Evaluation of Histological Findings of Airways of Rats Exposed to Highly Polluted Indoor Air in Offices

    Directory of Open Access Journals (Sweden)

    Martinsone Žanna

    2016-10-01

    Full Text Available Humans are exposed to chemicals and PM (particulate matter, including ultrafine particles (nanoparticles, mainly through inhalation. This creates a risk to their health. Another effect to exposure is expression of cytokines and their role in lung inflammation and morphpathogenesis. We conducted a pilot project based on testing of realistic exposure scenarios by describing morphological changes of the respiratory tract in Wistar rats (male during a 30-day exposure in office where there was high intensity of printing activities. Tracheal tissue of experimental animals had increasing concentrations of inflammatory interleukin IL-1 and decreasing concentrations of IL-6 and TNF-α. The lungs of the experimental animals tended to show focal infiltration of inflammatory cells, vascular plethora, focal and/or diffuse localisation of lymphatic nodules, and also vascular sclerosis and focal emphysema. The results suggested potential dangerous and adverse effect of poor indoor air quality (particles, including nanoparticles, and chemical compounds on respiratory tract tissue of rats.

  12. Influence of pretreatment of carbamates on dynamic pulmonary mechanics in rats exposed to sarin aerosols.

    Science.gov (United States)

    Husain, K; Kumar, P; Vijayaraghavan, R; Singh, R; Das Gupta, S

    1993-07-01

    The effect of pretreatment of two carbamates, pyridostigmine and physostigmine on dynamic pulmonary mechanics has been studied in rats exposed to sarin aerosols. Sign-free dose of pyridostigmine (0.075 mg/kg, i.m.) or physostigmine (0.1 mg/kg, i.m.) did not significantly alter the parameters of the dynamic pulmonary mechanics 20 min after treatment. However, sarin (51.2 mg/m3, for 15 min) depressed the respiratory rate, air flow and minute volume and enhanced the transthoracic pressure and tidal volume. Pretreatment with carbamates 20 min prior to sarin exposure significantly modified or counteracted the above induced changes. It is concluded that the protective effect of carbamates is mainly due to the correction of respiratory changes caused by sarin aerosols in rats.

  13. Morphogenesis of nasal tumors in rats exposed to hexamethylphosphoramide by inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K.P.; Trochimowicz, H.J.

    1984-02-01

    Hexamethylphosphoramide (HMPA) is used as a solvent, polymerization catalyst and, to some extent, as a deicing additive for jet fuels. Nasal tumors have been induced in rats by inhalation exposure to the compound for 6 to 24 months at concentrations of 50, 100, 400, and 4000 parts per billion (ppb), but not in rats exposed at 10 ppb for 24 months. Most nasal tumors were epidermoid carcinomas and developed from the respiratory epithelium or subepithelial nasal gland, both of which revealed squamous metaplasia or dysplasia in the anterior nasal cavity. The glandular cells appear to play an important role in developing epidermoid carcinomas in the nasal cavity. The ultrastructure of epidermoid carcinomas revealed abundant features of glandular differentiation in the neoplastic squamous cells. The morphological expression of glandular cell metamorphosis in the epidermoid carcinoma included intermediate cells showing both glandular and squamous differentiation, inter- or intracellular lumina, secretory vesicles, and mucus droplets in squamous cells and keratin plates.

  14. Mitochondrial oxidative stress and dysfunction in rat brain induced by carbofuran exposure.

    Science.gov (United States)

    Kamboj, Sukhdev Singh; Kumar, Vikas; Kamboj, Amit; Sandhir, Rajat

    2008-11-01

    Repeated low-dose exposure to carbofuran exerts its neurotoxic effects by non-cholinergic mechanisms. Emerging evidence indicates that oxidative stress plays an important role in carbofuran neurotoxicity after sub-chronic exposure. The purpose of the present study is to evaluate the role of mitochondrial oxidative stress and dysfunction as a primary event responsible for neurotoxic effects observed after sub-chronic carbofuran exposure. Carbofuran was administered to rats at a dose of 1 mg/kg orally for a period of 28 days. There was a significant inhibition in the activity of acetylcholinesterase (66.6%) in brain samples after 28 days of carbofuran exposure. Mitochondrial respiratory chain functions were assessed in terms of MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) reduction and activity of succinate dehydrogenase in isolated mitochondria. It was observed that carbofuran exposure significantly inhibited MTT reduction (31%) and succinate dehydrogenase activity (57%). This was accompanied by decrease in low-molecular weight thiols (66.6%) and total thiols (37.4%) and an increase in lipid peroxidation (43.7%) in the mitochondria isolated from carbofuran-exposed rat brain. The changes in mitochondrial oxidative stress and functions were associated with impaired cognitive and motor functions in the animals exposed to carbofuran as compared to the control animals. Based on these results, it is clear that carbofuran exerts its neurotoxicity by impairing mitochondrial functions leading to oxidative stress and neurobehavioral deficits.

  15. Functional brain networks underlying latent inhibition of conditioned disgust in rats.

    Science.gov (United States)

    Gasalla, Patricia; Begega, Azucena; Soto, Alberto; Dwyer, Dominic Michael; López, Matías

    2016-12-15

    The present experiment examined the neuronal networks involved in the latent inhibition of conditioned disgust by measuring brain oxidative metabolism. Rats were given nonreinforced intraoral (IO) exposure to saccharin (exposed groups) or water (non-exposed groups) followed by a conditioning trial in which the animals received an infusion of saccharin paired (or unpaired) with LiCl. On testing, taste reactivity responses displayed by the rats during the infusion of the saccharin were examined. Behavioral data showed that preexposure to saccharin attenuated the development of LiCl-induced conditioned disgust reactions, indicating that the effects of taste aversion on hedonic taste reactivity had been reduced. With respect to cumulative oxidative metabolic activity across the whole study period, the parabrachial nucleus was the only single region examined which showed differential activity between groups which received saccharin-LiCl pairings with and without prior non-reinforced saccharin exposure, suggesting a key role in the effects of latent inhibition of taste aversion learning. In addition, many functional connections between brain regions were revealed through correlational analysis of metabolic activity, in particular an accumbens-amygdala interaction that may be involved in both positive and negative hedonic responses.

  16. Sex- and Tissue-Specific Methylome Changes in Brains of Mice Perinatally Exposed to Lead

    Science.gov (United States)

    Sánchez-Martín, Francisco Javier; Lindquist, Diana M.; Landero-Figueroa, Julio; Zhang, Xiang; Chen, Jing; Cecil, Kim M.; Medvedovic, Mario; Puga, Alvaro

    2014-01-01

    Changes in DNA methylation and subsequent changes in gene expression regulation are the hallmarks of age- and tissue-dependent epigenetic drift and plasticity resulting from the combinatorial integration of genetic determinants and environmental cues. To determine whether perinatal lead exposure caused persistent DNA methylation changes in target tissues, we exposed mouse dams to 0, 3 or 30 ppm of lead acetate in drinking water for a period extending from 2 months prior to mating, through gestation, until weaning of pups at postnatal day-21, and analyzed whole-genome DNA methylation in brain cortex and hippocampus of 2-month old exposed and unexposed progeny. Lead exposure resulted in hypermethylation of three differentially methylated regions in the hippocampus of females, but not males. These regions mapped to Rn4.5s, Sfi1, and Rn45s loci in mouse chromosomes 2, 11 and 17, respectively. At a conservative fdr<0.001, 1,623 additional CpG sites were differentially methylated in female hippocampus, corresponding to 117 unique genes. Sixty of these genes were tested for mRNA expression and showed a trend towards negative correlation between mRNA expression and methylation in exposed females but not males. No statistically significant methylome changes were detected in male hippocampus or in cortex of either sex. We conclude that exposure to lead during embryonic life, a time when the organism is most sensitive to environmental cues, appears to have a sex- and tissue-specific effect on DNA methylation that may produce pathological or physiological deviations from the epigenetic plasticity operative in unexposed mice. PMID:25530354

  17. Prostaglandin E2 metabolism in rat brain: Role of the blood-brain interfaces

    Directory of Open Access Journals (Sweden)

    Strazielle Nathalie

    2008-03-01

    Full Text Available Abstract Background Prostaglandin E2 (PGE2 is involved in the regulation of synaptic activity and plasticity, and in brain maturation. It is also an important mediator of the central response to inflammatory challenges. The aim of this study was to evaluate the ability of the tissues forming the blood-brain interfaces to act as signal termination sites for PGE2 by metabolic inactivation. Methods The specific activity of 15-hydroxyprostaglandin dehydrogenase was measured in homogenates of microvessels, choroid plexuses and cerebral cortex isolated from postnatal and adult rat brain, and compared to the activity measured in peripheral organs which are established signal termination sites for prostaglandins. PGE2 metabolites produced ex vivo by choroid plexuses were identified and quantified by HPLC coupled to radiochemical detection. Results The data confirmed the absence of metabolic activity in brain parenchyma, and showed that no detectable activity was associated with brain microvessels forming the blood-brain barrier. By contrast, 15-hydroxyprostaglandin dehydrogenase activity was measured in both fourth and lateral ventricle choroid plexuses from 2-day-old rats, albeit at a lower level than in lung or kidney. The activity was barely detectable in adult choroidal tissue. Metabolic profiles indicated that isolated choroid plexus has the ability to metabolize PGE2, mainly into 13,14-dihydro-15-keto-PGE2. In short-term incubations, this metabolite distributed in the tissue rather than in the external medium, suggesting its release in the choroidal stroma. Conclusion The rat choroidal tissue has a significant ability to metabolize PGE2 during early postnatal life. This metabolic activity may participate in signal termination of centrally released PGE2 in the brain, or function as an enzymatic barrier acting to maintain PGE2 homeostasis in CSF during the critical early postnatal period of brain development.

  18. Differential Expression of Sirtuins in the Ageing Rat Brain

    Directory of Open Access Journals (Sweden)

    Gilles J. Guillemin

    2015-05-01

    Full Text Available Although there are seven mammalian sirtuins (SIRT1-7, little is known about their expression in the ageing brain. To characterise the change(s in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of ‘physiologically’ aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy ageing.

  19. Blast Exposure Induces Post-Traumatic Stress Disorder-Related Traits in a Rat Model of Mild Traumatic Brain Injury

    OpenAIRE

    Elder, Gregory A; Dorr, Nathan P.; De Gasperi, Rita; Gama Sosa, Miguel A.; Shaughness, Michael C.; Maudlin-Jeronimo, Eric; Hall, Aaron A; McCarron, Richard M.; Ahlers, Stephen T

    2012-01-01

    Blast related traumatic brain injury (TBI) has been a major cause of injury in the wars in Iraq and Afghanistan. A striking feature of the mild TBI (mTBI) cases has been the prominent association with post-traumatic stress disorder (PTSD). However, because of the overlapping symptoms, distinction between the two disorders has been difficult. We studied a rat model of mTBI in which adult male rats were exposed to repetitive blast injury while under anesthesia. Blast exposure induced a variety ...

  20. Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

    Directory of Open Access Journals (Sweden)

    Khedr LH

    2015-11-01

    Full Text Available Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chronic mild stress (CMS model and changes in hippocampal energy metabolism and the role of paroxetine (PAROX in ameliorating these changes. Male Wistar rats were divided into three groups: vehicle control, CMS-exposed rats, and CMS-exposed rats receiving PAROX (10 mg/kg/day intraperitoneally. Sucrose preference, open-field, and forced swimming tests were carried out. Corticosterone (CORT was measured in serum, while adenosine triphosphate and its metabolites, cytosolic cytochrome-c (Cyt-c, caspase-3 (Casp-3, as well as nitric oxide metabolites (NOx were measured in hippocampal tissue homogenates. CMS-exposed rats showed a decrease in sucrose preference as well as body weight compared to control, which was reversed by PAROX. The latter further ameliorated the CMS-induced elevation of CORT in serum (91.71±1.77 ng/mL vs 124.5±4.44 ng/mL, P<0.001 as well as the changes in adenosine triphosphate/adenosine diphosphate (3.76±0.02 nmol/mg protein vs 1.07±0.01 nmol/mg protein, P<0.001. Furthermore, PAROX reduced the expression of Cyt-c and Casp-3, as well as restoring NOx levels. This study highlights the role of PAROX in reversing depressive behavior associated with stress-induced apoptosis and changes in hippocampal energy metabolism in the CMS model of depression. Keywords: rats, CMS, hippocampus, paroxetine, apoptosis, adenine nucleotides, cytochrome-c, caspase-3

  1. Brain deposition and neurotoxicity of manganese in adult mice exposed via the drinking water.

    Science.gov (United States)

    Krishna, Saritha; Dodd, Celia A; Hekmatyar, Shahryar K; Filipov, Nikolay M

    2014-01-01

    Natural leaching processes and/or anthropogenic contamination can result in ground water concentrations of the essential metal manganese (Mn) that far exceed the current regulatory standards. Neurological consequences of Mn drinking water (DW) overexposure to experimental animals, i.e., mice, including its brain deposition/distribution and behavioral effects are understudied. Adult male C57BL/6 mice were exposed to Mn via the DW for 8 weeks. After 5 weeks of Mn exposure, magnetic resonance imaging revealed significant Mn deposition in all examined brain regions; the degree of Mn deposition did not increase further a week later. Behaviorally, early hyperactivity and more time spent in the center of the arenas in an open field test, decreased forelimb grip strength and less time swimming in a forced swim test were observed after 6 weeks of Mn DW exposure. Eight-week Mn DW exposure did not alter striatal dopamine, its metabolites, or the expression of key dopamine homeostatic proteins, but it significantly increased striatal 5-hydroxyindoleacetic acid (a serotonin metabolite) levels, without affecting the levels of serotonin itself. Increased expression (mRNA) of glial fibrillary acidic protein (GFAP, an astrocyte activation marker), heme oxygenase-1 and inducible nitric oxide synthase (oxidative and nitrosative stress markers, respectively) were observed 8 weeks post-Mn DW exposure in the substantia nigra. Besides mRNA increases, GFAP protein expression was increased in the substantia nigra pars reticulata. In summary, the neurobehavioral deficits, characterized by locomotor and emotional perturbations, and nigral glial activation associated with significant brain Mn deposition are among the early signs of Mn neurotoxicity caused by DW overexposure.

  2. In vivo occupancy of female rat brain estrogen receptors by 17beta-estradiol and tamoxifen.

    Science.gov (United States)

    Pareto, D; Alvarado, M; Hanrahan, S M; Biegon, A

    2004-11-01

    Estrogens or antiestrogens are currently used by millions of women, but the interaction of these hormonal agents with brain estrogen receptors (ER) in vivo has not been characterized to date. Our goal was to assess, in vivo, the extent and regional distribution of brain ER occupancy in rats chronically exposed to 17beta-estradiol (E(2)) or tamoxifen (TAM). For that purpose, female ovariectomized Sprague-Dawley rats were implanted with subcutaneous pellets containing either placebo (OVX), E(2), or TAM for 3 weeks. ER occupancy in grossly dissected regions was quantified with 16alpha-[(18)F]fluoroestradiol ([(18)F]FES). Both E(2) and TAM produced significant decreases in radioligand uptake in the brain although the effect of E(2) was larger and more widespread than the effect of TAM. Detailed regional analysis of the interaction was then undertaken using a radioiodinated ligand, 11beta-methoxy-16alpha-[(125)I]iodo-estradiol ([(125)I]MIE(2)), and quantitative ex vivo autoradiography. E(2) treatment resulted in near-complete (86.6 +/- 17.5%) inhibition of radioligand accumulation throughout the brain, while ER occupancy in the TAM group showed a marked regional distribution such that percentage inhibition ranged from 40.5 +/- 15.6 in the ventrolateral part of the ventromedial hypothalamic nucleus to 84.6 +/- 4.5 in the cortical amygdala. These results show that exposure to pharmacologically relevant levels of TAM produces a variable, region-specific pattern of brain ER occupancy, which may be influenced by the regional proportion of ER receptor subtypes. These findings may partially explain the highly variable and region-specific effects observed in neurochemical, metabolic, and functional studies of the effects of TAM in the brain of experimental animals as well as human subjects.

  3. Downregulation of CREB expression in Alzheimer's brain and in Aβ-treated rat hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Pham Serena

    2011-08-01

    Full Text Available Abstract Background Oxidative stress plays an important role in neuronal dysfunction and neuron loss in Alzheimer's brain. Previous studies have reported downregulation of CREB-mediated transcription by oxidative stress and Aβ. The promoter for CREB itself contains cyclic AMP response elements. Therefore, we examined the expression of CREB in the hippocampal neurons of Tg2576 mice, AD post-mortem brain and in cultured rat hippocampal neurons exposed to Aβ aggregates. Results Laser Capture Microdissection of hippocampal neurons from Tg2576 mouse brain revealed decreases in the mRNA levels of CREB and its target, BDNF. Immunohistochemical analysis of Tg2576 mouse brain showed decreases in CREB levels in hippocampus and cortex. Markers of oxidative stress were detected in transgenic mouse brain and decreased CREB staining was observed in regions showing abundance of astrocytes. There was also an inverse correlation between SDS-extracted Aβ and CREB protein levels in Alzheimer's post-mortem hippocampal samples. The levels of CREB-regulated BDNF and BIRC3, a caspase inhibitor, decreased and the active cleaved form of caspase-9, a marker for the intrinsic pathway of apoptosis, was elevated in these samples. Exposure of rat primary hippocampal neurons to Aβ fibrils decreased CREB promoter activity. Decrease in CREB mRNA levels in Aβ-treated neurons was reversed by the antioxidant, N-acetyl cysteine. Overexpression of CREB by adenoviral transduction led to significant protection against Aβ-induced neuronal apoptosis. Conclusions Our findings suggest that chronic downregulation of CREB-mediated transcription results in decrease of CREB content in the hippocampal neurons of AD brain which may contribute to exacerbation of disease progression.

  4. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Boberg, Julie; Vinggaard, Anne Marie

    2013-01-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T4) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout...... gestation and lactation. Total T4 serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T4 in dams, but no significant effects on T4 levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure...... through maternal milk, a second study using direct per oral pup exposure from postnatal day 3–16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T4 reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing...

  5. Postnatal development of aminopeptidase (arylamidase) activity in rat brain.

    Science.gov (United States)

    de Gandarias, J M; Ramírez, M; Zulaica, J; Iribar, C; Casis, L

    1989-01-01

    Changes in the activities of Leu- and Arg-arylamidase in rat frontal and parietal cortices and the subcortical area (including thalamus, hypothalamus, and striatum) were examined in the 2nd, 4th, 8th, 12th, and 24th weeks of life. Average levels found in the subcortical region were greater than those in the cortical areas. The most marked changes in enzymatic activity in the course of brain development were found in the subcortical structure. Leu-arylamidase activity increased from the 2nd week up to the 8th week, returning to the 2nd week level at the 12th and 24th weeks. The maximum levels of Arg-arylamidase activity were found at the 4th and 8th weeks. These data suggest that proteolytic activity is involved in the postnatal development of rat brain.

  6. Elevated brain aluminium and early onset Alzheimer’s disease in an individual occupationally exposed to aluminium: a case report

    OpenAIRE

    2014-01-01

    Introduction Aluminium is a known neurotoxin and occupational exposure to aluminium has been implicated in neurological disease including Alzheimer’s disease. Here we present the first comprehensive and unequivocal data demonstrating significantly elevated brain aluminium content in an individual occupationally exposed to aluminium. Case presentation A 66-year-old Caucasian man who died with Alzheimer’s disease showed significantly elevated brain aluminium content, 2.98 (2.73) μg/g dry weight...

  7. Neuroinflammation and Behavior in HIV-1 Transgenic Rats Exposed to Chronic Adolescent Stress

    Science.gov (United States)

    Rowson, Sydney A.; Harrell, Constance S.; Bekhbat, Mandakh; Gangavelli, Apoorva; Wu, Matthew J.; Kelly, Sean D.; Reddy, Renuka; Neigh, Gretchen N.

    2016-01-01

    Highly active antiretroviral therapy (HAART) has improved prognosis for people living with HIV (PLWH) and dramatically reduced the incidence of AIDS. However, even when viral load is controlled, PLWH develop psychiatric and neurological disorders more frequently than those living without HIV. Adolescents with HIV are particularly susceptible to the development of psychiatric illnesses and neurocognitive impairments. While both psychiatric and neurocognitive disorders have been found to be exacerbated by stress, the extent to which chronic stress and HIV-1 viral proteins interact to impact behavior and relevant neuroinflammatory processes is unknown. Determination of the individual contributions of stress and HIV to neuropsychiatric disorders is heavily confounded in humans. In order to isolate the influence of HIV-1 proteins and chronic stress on behavior and neuroinflammation, we employed the HIV-1 transgenic (Tg) rat model, which expresses HIV-1 proteins with a gag and pol deletion, allowing for viral protein expression without viral replication. This Tg line has been characterized as a model of HAART-controlled HIV-1 infection due to the lack of viral replication but continued presence of HIV-1 proteins. We exposed male and female adolescent HIV-1 Tg rats to a mixed-modality chronic stress paradigm consisting of isolation, social defeat and restraint, and assessed behavior, cerebral vascularization, and neuroinflammatory endpoints. Stress, sex, and presence of the HIV-1 transgene impacted weight gain in adolescent rats. Female HIV-1 Tg rats showed decreases in central tendency during the light cycle in the open field regardless of stress exposure. Both male and female HIV-1 Tg rats exhibited decreased investigative behavior in the novel object recognition task, but no memory impairments. Adolescent stress had no effect on the tested behaviors. Microglia in female HIV-1 Tg rats exhibited a hyper-ramified structure, and gene expression of complement factor B was

  8. Neuroinflammation and Behavior in HIV-1 Transgenic Rats Exposed to Chronic Adolescent Stress.

    Science.gov (United States)

    Rowson, Sydney A; Harrell, Constance S; Bekhbat, Mandakh; Gangavelli, Apoorva; Wu, Matthew J; Kelly, Sean D; Reddy, Renuka; Neigh, Gretchen N

    2016-01-01

    Highly active antiretroviral therapy (HAART) has improved prognosis for people living with HIV (PLWH) and dramatically reduced the incidence of AIDS. However, even when viral load is controlled, PLWH develop psychiatric and neurological disorders more frequently than those living without HIV. Adolescents with HIV are particularly susceptible to the development of psychiatric illnesses and neurocognitive impairments. While both psychiatric and neurocognitive disorders have been found to be exacerbated by stress, the extent to which chronic stress and HIV-1 viral proteins interact to impact behavior and relevant neuroinflammatory processes is unknown. Determination of the individual contributions of stress and HIV to neuropsychiatric disorders is heavily confounded in humans. In order to isolate the influence of HIV-1 proteins and chronic stress on behavior and neuroinflammation, we employed the HIV-1 transgenic (Tg) rat model, which expresses HIV-1 proteins with a gag and pol deletion, allowing for viral protein expression without viral replication. This Tg line has been characterized as a model of HAART-controlled HIV-1 infection due to the lack of viral replication but continued presence of HIV-1 proteins. We exposed male and female adolescent HIV-1 Tg rats to a mixed-modality chronic stress paradigm consisting of isolation, social defeat and restraint, and assessed behavior, cerebral vascularization, and neuroinflammatory endpoints. Stress, sex, and presence of the HIV-1 transgene impacted weight gain in adolescent rats. Female HIV-1 Tg rats showed decreases in central tendency during the light cycle in the open field regardless of stress exposure. Both male and female HIV-1 Tg rats exhibited decreased investigative behavior in the novel object recognition task, but no memory impairments. Adolescent stress had no effect on the tested behaviors. Microglia in female HIV-1 Tg rats exhibited a hyper-ramified structure, and gene expression of complement factor B was

  9. 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

  10. Predator cat odors activate sexual arousal pathways in brains of Toxoplasma gondii infected rats.

    Directory of Open Access Journals (Sweden)

    Patrick K House

    Full Text Available Cat odors induce rapid, innate and stereotyped defensive behaviors in rats at first exposure, a presumed response to the evolutionary pressures of predation. Bizarrely, rats infected with the brain parasite Toxoplasma gondii approach the cat odors they typically avoid. Since the protozoan Toxoplasma requires the cat to sexually reproduce, this change in host behavior is thought to be a remarkable example of a parasite manipulating a mammalian host for its own benefit. Toxoplasma does not influence host response to non-feline predator odor nor does it alter behavior on olfactory, social, fear or anxiety tests, arguing for specific manipulation in the processing of cat odor. We report that Toxoplasma infection alters neural activity in limbic brain areas necessary for innate defensive behavior in response to cat odor. Moreover, Toxoplasma increases activity in nearby limbic regions of sexual attraction when the rat is exposed to cat urine, compelling evidence that Toxoplasma overwhelms the innate fear response by causing, in its stead, a type of sexual attraction to the normally aversive cat odor.

  11. 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.

  12. 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.

  13. Cultured human embryonic neocortical cells survive and grow in infarcted cavities of adult rat brains and interconnect with host brain

    Institute of Scientific and Technical Information of China (English)

    ZENG Jin-sheng; YU Jian; CUI Chun-mei; ZHAO Zhan; HONG Hua; SHENG Wen-li; TAO Yu-qian; LI Ling; HUANG Ru-xun

    2005-01-01

    Background There are no reports on exnografting cultured human fetal neocortical cells in this infracted cavities of adult rat brains. This study was undertaken to observe whether cultured human cortical neurons and astrocytes can survive and grow in the infarcted cavities of adult rat brains and whether they interconnect with host brains.Methods The right middle cerebral artery was ligated distal to the striatal branches in 16 adult stroke-prone renovascular hypertensive rats. One week later, cultured cells from human embryonic cerebral cortexes were stereotaxically transferred to the infarcted cavity of 11 rats. The other 5 rats receiving sham transplants served as controls. For immunosuppression, all transplanted rats received intraperitoneal injection of cyclosporine A daily starting on the day of grafting. Immunohistochemistry for glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, and microtubule associated protein-2 (MAP-2) was performed on brain sections perfused in situ 8 weeks after transplantation.Results Grafts in the infarcted cavities of 6 of 10 surviving rats consisted of bands of neurons with an immature appearance, bundles of fibers, and GFAP-immunopositive astrocytes, which were unevenly distributed. The grafts were rich in synaptophysin, neurofilament, and MAP2-positive neurons with long processes. The graft/host border was diffuse with dendrites apparently bridging over to the host brain, into which neurofilament immunopositive fibers protruded. Conclusion Cultured human fetal brain cells can survive and grow in the infarcted cavities of immunodepressed rats and integrate with the host brain.

  14. 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.

  15. Brain oxidative stress induced by obstructive jaundice in rats.

    Science.gov (United States)

    Chroni, Elisabeth; Patsoukis, Nikolaos; Karageorgos, Nikolaos; Konstantinou, Dimitris; Georgiou, Christos

    2006-02-01

    The effect of experimental obstructive jaundice on the oxidative status of brain tissues in rats was examined. Twenty-four male Wistar rats were divided into 4 groups: Group I was the control, group II was the sham operated, and groups III and IV were bile duct ligated and killed on the 5th and the 10th day, respectively. Oxidative stress was assessed by measuring the thiol redox state (protein and nonprotein components) and lipid peroxidation level variations in samples from the cerebral cortex, midbrain, and cerebellar tissue in all animals. Results indicated the presence of oxidative stress in the jaundiced animals that was more pronounced on the 10th day as indicated by a decrease in reduced glutathione and protein thiol and an increase in protein disulphide and lipid peroxidation. A dramatic elevation of the level of total nonprotein mixed disulphide level was found specifically in the midbrain in the 10th day group. This suggests an accumulation of nonprotein disulfides other than oxidized glutathione, which remained unchanged, in this particular brain area. This study showed a correlation between experimental obstructive jaundice and the oxidative stress in the rats' brain, implying that a similar pathogenetic mechanism may play a key role in cholestatic liver disease, resulting in hepatic encephalopathy in humans.

  16. Gelation and fodrin purification from rat brain extracts.

    Science.gov (United States)

    Levilliers, N; Péron-Renner, M; Coffe, G; Pudles, J

    1986-06-03

    Extracts from rat brain tissue have been shown to give rise to a gel which exhibits the following features. It is mainly enriched in actin and in a high-molecular-weight protein with polypeptide chains of 235 and 240 kDa, which we identified as fodrin. Tubulin is also a major component of the gel but it appears to be trapped non-specifically during the gelation process. Gelation is pH-, ionic strength- and Ca2+-concentration-dependent, and is optimal under the conditions which promote the interaction between polymerized actin and fodrin. In a similar way to that described for the purification of rat brain actin (Levilliers, N., Péron-Renner, M., Coffe, G. and Pudles, J. (1984) Biochimie 66, 531-537), we used the gelation system as a selective means of recovering fodrin from the mixture of a low-ionic-strength extract from whole rat brain and a high-ionic-strength extract of the particulate fraction. From this gel, fodrin was purified with a good yield by a simple procedure involving gel dissociation in 0.5 M KCl and depolymerization in 0.7 M KI, Bio-Gel A-15m chromatography, followed by ammonium sulfate precipitation.

  17. Oligodendrocyte transcription factor 1 mRNA and protein expression in organotypic rat brain slices

    Institute of Scientific and Technical Information of China (English)

    Hong Cui; Lijun Yang; Dezhuang Huang; Wandong Zhang; Weijuan Han; Yanqing Yao; Wenxing Jiang

    2010-01-01

    Numerous studies have confirmed that oligodendrocyte transcription factor 1 (Olig-1) is vital for myelin repair. However, the effects of hypoxia and ischemia on Olig-1 expression remain unknown.In this study, Olig-1 mRNA and protein expressions were analyzed by in situ hybridization and immunohistochemistry, to determine the expression profile of Olig-1 in rat brain slices exposed to hypoxia and ischemia. Brains were obtained from 2-day-old Sprague-Dawley rats, and sections were randomly assigned to control and hypoxia/ischemia groups. Hematoxylin-eosin staining revealed karyorrhexis and karyopyknosis in cells from the hypoxia/ischemia group. Under electron microscopy, mitochondria swelling and neuropil edema were observed in the hypoxia/ischemia group. Olig-1 mRNA and protein expressions were increased at 1 day after hypoxia and ischemia treatment. These results suggest that in situ hybridization and immunohistochemistry could be used simultaneously to detect mRNA and protein expression in brain slices.

  18. 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.

  19. Cytomorphometric changes in hippocampal CA1 neurons exposed to simulated microgravity using rats as model

    Directory of Open Access Journals (Sweden)

    Amit eRanjan

    2014-05-01

    Full Text Available Microgravity and sleep loss lead to cognitive and learning deficits. These behavioral alterations are likely to be associated with cytomorphological changes and loss of neurons. To understand the phenomenon, we exposed rats (225-275g to 14 days simulated microgravity (SMg and compared its effects on CA1 hippocampal neuronal plasticity, with that of normal cage control rats. We observed that the mean area, perimeter, synaptic cleft and length of active zone of CA1 hippocampal neurons significantly decreased while dendritic arborization and number of spines significantly increased in SMg group as compared with controls. The mean thickness of the post synaptic density and total dendritic length remained unaltered. The changes may be a compensatory effect induced by exposure to microgravity; however, the effects may be transient or permanent, which need further study. These findings may be useful for designing effective prevention for those, including the astronauts, exposed to microgravity. Further, subject to confirmation we propose that SMg exposure might be useful for recovery of stroke patients.

  20. Uranium XAFS analysis of kidney from rats exposed to uranium

    Science.gov (United States)

    Kitahara, Keisuke; Numako, Chiya; Terada, Yasuko; Nitta, Kiyohumi; Homma-Takeda, Shino

    2017-01-01

    The kidney is the critical target of uranium exposure because uranium accumulates in the proximal tubules and causes tubular damage, but the chemical nature of uranium in kidney, such as its chemical status in the toxic target site, is poorly understood. Micro-X-ray absorption fine-structure (µXAFS) analysis was used to examine renal thin sections of rats exposed to uranyl acetate. The U L III-edge X-ray absorption near-edge structure spectra of bulk renal specimens obtained at various toxicological phases were similar to that of uranyl acetate: their edge position did not shift compared with that of uranyl acetate (17.175 keV) although the peak widths for some kidney specimens were slightly narrowed. µXAFS measurements of spots of concentrated uranium in the micro-regions of the proximal tubules showed that the edge jump slightly shifted to lower energy. The results suggest that most uranium accumulated in kidney was uranium (VI) but a portion might have been biotransformed in rats exposed to uranyl acetate. PMID:28244440

  1. Simvastatin treatment exerts antidepressant-like effect in rats exposed to chronic mild stress.

    Science.gov (United States)

    Lin, Pao-Yen; Chang, Alice Y W; Lin, Tsu-Kung

    2014-09-01

    Hyperlipidemia is associated with increased risk of coronary artery disease and stroke, both of which, in turn, are risk factors of old-age depression. Statins are extensively used for decreasing cholesterol levels. Clinical investigations revealed that long-term use of statins appeared to be associated with a lower risk of anxiety and depression. However, the antidepressant property of statins has not been well examined. This study aimed at examining the antidepressant-like effects of statins in rats exposed to chronic mild stress (CMS). We found that animals exposed to CMS for 4 weeks developed depressive-like state, shown by forced swim test and sucrose preference test. However, these CMS-induced behavioral changes were reversed by simvastatin (5 or 10mg/kg/day) for 14 days, comparable to imipramine (10mg/kg/day) treatment. Locomotor activity and anxiety-like behaviors were not altered by CMS or these treatments. These results demonstrated antidepressant-like effects of statin in CMS model of rats and suggested the potential that statins could be used to facilitate antidepressant treatment in clinical setting.

  2. 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.

  3. 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.

  4. Evaluation of reproductive function of female rats exposed to radiofrequency fields (27. 12 MHz) near a shortwave diathermy device

    Energy Technology Data Exchange (ETDEWEB)

    Brown-Woodman, P.D.; Hadley, J.A.; Richardson, L.; Bright, D.; Porter, D.

    1989-04-01

    In recent years, there has been increased concern regarding effects of operator exposure to the electromagnetic (EM) field associated with shortwave diathermy devices. The present study was designed to investigate the effects, on rats, of repeated exposure to such an EM field. Following repeated exposure for 5 wk, a reduction in fertility occurred as indicated by a reduced number of matings in exposed rats compared to sham-irradiated rats and a reduction in the number of rats that conceived after mating. The data suggest that female operators could experience reduced fertility, if they remained close to the console for prolonged periods. This has particular significant for the physiotherapy profession.

  5. Effects of protein malnutrition on oxidative status in rat brain.

    Science.gov (United States)

    Feoli, Ana M; Siqueira, Ionara R; Almeida, Lúcia; Tramontina, Ana C; Vanzella, Cláudia; Sbaraini, Sabrina; Schweigert, Ingrid D; Netto, Carlos A; Perry, Marcos L S; Gonçalves, Carlos A

    2006-02-01

    This study evaluated the effects of protein malnutrition on oxidative status in rat brain areas. We investigated various parameters of oxidative status, free radical content (dichlorofluorescein formation), indexes of damage to lipid (thiobarbituric acid-reactive substances assay), and protein damage (tryptophan and tyrosine content) in addition to total antioxidant reactivity levels and antioxidant enzyme activities of superoxide dismutase, glutathione peroxidase, and catalase in different cerebral regions (cortex, hippocampus, and cerebellum) from rats subjected to prenatal and postnatal protein malnutrition (control 25% casein and protein malnutrition 7% casein). Protein malnutrition altered various parameters of oxidative stress, especially damage to macromolecules. Free radical content was unchanged by protein malnutrition. There was an increase in levels of thiobarbituric acid-reactive substances, the index of lipid peroxidation, in the cerebellum and cerebral cortex (P brain structures (P malnutrition increased oxidative damage to lipids and proteins from the studied brain areas. These results may be an indication of an important mechanism for changes in brain development that are caused by protein malnutrition.

  6. 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.

  7. Ultrasonic energy as a tool to overcome some drawbacks in the determination of lead in brain tissue and urine of rats.

    Science.gov (United States)

    Guimarães, D; Santos, J P; Carvalho, M L; Vale, G; Santos, H M; Geraldes, V; Rocha, I; Capelo, J L

    2011-10-30

    An ultrasonic assisted solid-liquid extraction method was developed to determine the level of lead in the brain and urine of rats. Lead was determined by electrothermal atomic absorption spectrometry with longitudinal-Zeeman background correction. Several analytical drawbacks were addressed and overcome, namely small brain sample mass and the formation of precipitate in the urine samples. Utrasonication provided by an ultrasonic probe succeeded in extracting lead from brain samples. Furthermore, it was demonstrated that the formation of a precipitate lowered the lead content in the liquid phase of the urine. Lead was back extracted from the precipitate to the liquid phase with the aid of ultrasonic energy and acidifying the urine with 10% v/v nitric acid. A microwave-assisted acid digestion protocol was used to check the completeness of the lead extraction. The within bath and between bath precision was 5% (n=9) and 7% (n=3) respectively. The limit of quantification was 1.05 μg g(-1) for brain samples and 2.1 μg L(-1) for urine samples. A total of 6 samples of urine and 12 samples of brain from control rats and another 6 samples of urine and 12 samples of brain from rats fed with tap water rich in lead acetate were used in this research. Lead levels in brain and urine from exposed rats ranged from 1.9 ± 0.2 μg g(-1) to 3.5 ± 0.2 μg g(-1) and from 752 ± 56 μg L(-1) to 60.9 ± 1.2 mg L(-1) respectively. Statistically significant differences of levels of lead in brain and urine were found between exposed and non exposed rats.

  8. Distinct transcriptional changes in donor kidneys upon brain death induction in rats : Insights in the processes of brain death

    NARCIS (Netherlands)

    Schuurs, TA; Gerbens, F; van der Hoeven, JAB; Ottens, PJ; Kooi, KA; Leuvenink, HGD; Hofstra, RMW; Ploeg, RJ

    2004-01-01

    Brain death affects hormone regulation, inflammatory reactivity and hemodynamic stability. In transplant models, donor organs retrieved from brain dead (BD) rats suffer from increased rates of primary nonfunction and lower graft survival. To unravel the mechanisms behind brain death we have performe

  9. Influence of histidine on zinc transport into rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Atsushi; Suzuki, Mai; Okada, Shoji; Oku, Naoto [Shizuoka Univ. (Japan). School of Pharmaceutical Sciences

    2000-06-01

    The brain of rats injected intravenously with {sup 65}Zn-His or {sup 65}ZnCl{sub 2} was subjected to autoradiography to study the role of histidine on zinc transport into the brain. One hour after injection, the radioactivity from {sup 65}Zn-His was largely concentrated in the choroid plexus in the ventricles. Six days after injection, the radioactivity from {sup 65}Zn-His was relatively concentrated in the hippocampal CA3 and dentate gyrus and the amygdala. The relative distribution of {sup 65}Zn-His in the brain was similar to that of {sup 65}ZnCl{sub 2} group at both 1 h and 6 days, suggesting that histidine may participate in zinc uptake in the brain. On the other hand, the clearance of the {sup 65}Zn-His group from the blood was higher than that of the {sup 65}ZnCl{sub 2} group. Brain uptake of the former was lower than that of the latter both 1 h and 6 days after injection. These results suggest that zinc uptake in the brain is influenced by histidine levels in the bloodstream. (author)

  10. 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.

  11. Impact of Seasonal Variant Temperatures and Laboratory Room Ambient Temperature on Mortality of Rats with Ischemic Brain Injury

    Science.gov (United States)

    Gopalakrishanan, Sivakumar; Babu, Mg. Ramesh; Thangarajan, Rajesh; Punja, Dhiren; Jaganath, Vidyadhara Devarunda; Kanth, Akriti B.; Rao, Mohandas

    2016-01-01

    Introduction A popular rat model for hypoperfusion ischemic brain injury is bilateral common carotid artery occlusion (BCCAO). BCCAO surgery when performed in varying geographical locations and during different seasons of the year is reported to have variable mortality rates. Studies have also documented the diminishing influence of Ketamine-Xylazine (KT-XY) on thermoregulatory functions in rodents. Aim To explore the impact of seasonal variant temperatures and laboratory room ambient temperatures on mortality of rats following BCCAO surgery. Materials and Methods The study has two parts: 1 The first part is an analysis of a three year retrospective data to explore the association between the geographical season (hot summer and cold winter) induced laboratory room ambient temperature variations and the mortality rate in KT-XY anaesthetized BCCAO rats. 2. The second part investigated the effect of conditioned laboratory room ambient temperature (CAT) (23-250C) in KT-XY anaesthetized BCCAO group of rats. Rats were divided into 4 groups(n =8/group) as-Normal control, BCCAO and Sham BCCAO where they were all exposed to unconditioned ambient temperature (UCAT) during their surgery and postoperative care. And finally fourth group rats exposed to CAT during the BCCAO surgery and postoperative care. Results Pearson’s chi-square test indicates a significantly high association (p<0.006) between post-BCCAO mortality and hot season of the year. CAT during the hot season reduced the mortality rate (24% less) in post- BCCAO rats compared to the rats of UCAT. Conclusion Despite seasonal variations in temperature, conditioning the laboratory room ambient temperatures to 23–250C, induces hypothermia in KT-XY anaesthetized ischemic brain injured rodents and improves their survival rate. PMID:27190796

  12. Effects of High-Butterfat Diet on Embryo Implantation in Female Rats Exposed to Bisphenol A.

    Science.gov (United States)

    Martinez, Alan M; Cheong, Ana; Ying, Jun; Xue, Jingchuan; Kannan, Kurunthachalam; Leung, Yuet-Kin; Thomas, Michael A; Ho, Shuk-Mei

    2015-12-01

    Bisphenol A (BPA) is an endocrine disruptor associated with poor pregnancy outcomes in human and rodents. The effects of butterfat diets on embryo implantation and whether it modifies BPA's actions are currently unknown. We aimed to determine the effects of butterfat diet on embryo implantation success in female rats exposed to an environmentally relevant dose of BPA. Female Sprague-Dawley rats were exposed to dietary butterfat (10% or 39% kcal/kg body weight [BW]) in the presence or absence of BPA (250 μg/kg BW) or ethinylestradiol (0.1 μg/kg BW) shortly before and during pregnancy to assess embryo implantation potentials by preimplantation development and transport, in vitro blastulation, outgrowth, and implantation. On gestational day (GD) 4.5, rats treated with BPA alone had higher serum total BPA level (2.3-3.7 ng/ml). They had more late-stage preimplantation embryos, whereas those receiving high butterfat (HBF) diet had the most advanced-stage embryos; dams cotreated with HBF and BPA had the most number of advanced embryos. BPA markedly delayed embryo transport to the uterus, but neither amount of butterfat had modifying effects. An in vitro implantation assay showed HBF doubled the outgrowth area, with BPA having no effect. In vivo, BPA reduced the number of implanted embryos on GD8, and cotreatment with HBF eliminated this adverse effect. HBF diet overall resulted in more and larger GD8 embryos. This study reveals the implantation disruptive effects of maternal exposure to an environmentally relevant dose of BPA and identifies HBF diet as a modifier of BPA in promoting early embryonic health.

  13. Structural characterization of rat ventricular tissue exposed to the smoke of two types of waterpipe

    Directory of Open Access Journals (Sweden)

    Wajdy Al-Awaida

    2015-10-01

    Full Text Available Objective(s:this study focused on the effect of waterpipe smoke exposure toxicity on the structure of albino rat’s ventricular tissue and their recovery. Materials and Methods: Albino rats were divided into three groups: control, flavored, and unflavored. The control group was exposed to normal air while the flavored and unflavored groups were exposed to waterpipe smoke for a period of 90 days. Each group was followed by a period of 90 days of fresh air exposure. Following each period, the ventricular tissue was removed for biochemical and histopathological studies. Results:The ventricular tissues of waterpipe exposed rats showed some degree of separation between cardiac muscle fibers, infiltration of lymphocytes, and congestion of blood vessel. Also, thin cross sections of ventricular cells revealed pleomorphic mitochondria with partially disrupted cristae, partial disruption of the myofibrils, and deposited toxic materials. The unflavored waterpipe has more deleterious effects on heart ventricular tissues than the flavored one. Waterpipe smoke didn't induce apoptosis in the ventricular tissue. We also found very high levels of plasma thiocyanate after exposure to smoke in the flavored and unflavored groups, while the control group showed no increase. After the recovery period, those tissues showed partial recovery. Conclusion: Waterpipe smoke induces structural changes in the heart ventricle tissues, causing a negative impact on the capacity of the cardiac muscle for pumping blood and may lead to heart attack due to accumulation of free radicals and tissue inflammation. Cessation of smoking is important in returning most of these changes to their normal structure.

  14. Steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation

    Directory of Open Access Journals (Sweden)

    Gisele Negro Lima

    2015-02-01

    Full Text Available OBJECTIVE: To analyze steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation. METHODS: Thirty-two virgin adult female rats were randomized to two groups as follows: the control group GI received vehicle and the experimental group GII received melatonin supplementation (10 µg/night per animal for 60 consecutive days. After the treatment, animals were anesthetized and the collected ovaries were immediately placed in liquid nitrogen for complementary deoxyribonucleic acid microarray analyses. A GeneChip¯ Kit Rat Genome 230 2.0 Affymetrix Array was used for gene analysis and the experiment was repeated three times for each group. The results were normalized with the GeneChip¯ Operating Software program and confirmed through analysis with the secondary deoxyribonucleic acid-Chip Analyzer (dChip software. The data were confirmed by real-time reverse transcription polymerase chain reaction analysis. Genes related to ovarian function were further confirmed by immunohistochemistry. RESULTS: We found the upregulation of the type 9 adenylate cyclase and inhibin beta B genes and the downregulation of the cyclic adenosine monophosphate response element modulator and cytochrome P450 family 17a1 genes in the ovarian tissue of GII compared to those of the control group. CONCLUSION: Our data suggest that melatonin supplementation decreases gene expression of cyclic adenosine monophosphate, which changes ovarian steroidogenesis.

  15. Lead exposure increases oxidative stress in the gastric mucosa of HCI/ethanol-exposed rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the role of reactive oxygen species in the ulcer-aggravating effect of lead in albino rats.METHODS: Albino Wistar rats were randomly divided into three groups and treated orally with 100 mg/L (low dose) or 5000 mg/L (high dose) of lead acetate for 15 wk. A third group received saline and served as control.At the end of wk 15, colorimetric assays were applied to determine the concentrations of total protein and nitrite, the activities of the oxidative enzymes catalase and superoxide dismutase, and lipid peroxidation in homogenized gastric mucosal samples.RESULTS: Exposure of rats to lead significantly increased the gastric mucosal damage caused by acidified ethanol. Although the basal gastric acid secretory rate was not significantly altered, the maximal response of the stomach to histamine was significantly higher in the lead-exposed animals than in the unexposed control group. Exposure to low and high levels of lead significantly increased gastric lipid peroxidation to 183.2% ± 12.7% and 226.1% ± 6.8% of control values respectively (P < 0.0). On the other hand, lead exposure significantly decreased catalase and superoxide dismutase (SOD) activities and the amount of nitrite in gastric mucosal samples.CONCLUSION: Lead increases the formation of gastric ulcers by interfering with the oxidative metabolism in the stomach.

  16. Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Carolina Dizioli Rodrigues de Oliveira

    2011-12-01

    Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

  17. Changes on fecal microbiota in rats exposed to permethrin during postnatal development.

    Science.gov (United States)

    Nasuti, Cinzia; Coman, Maria Magdalena; Olek, Robert A; Fiorini, Dennis; Verdenelli, Maria Cristina; Cecchini, Cinzia; Silvi, Stefania; Fedeli, Donatella; Gabbianelli, Rosita

    2016-06-01

    Alteration of the gut microbiota through diet and environmental contaminants may disturb the mammalian digestive system, leading to various diseases. Because most exposure to environmentally pyrethroid pesticides such as permethrin (PERM) occurs through the diet, the commensal gut microbiota is likely to be exposed to PERM. The study aimed at evaluating the effect of low-dose exposure to PERM in early life on the composition of fecal microbiota in rats. Over a 4-month follow-up period, fecal microbiota and short-chain fatty acids were measured in order to identify possible differences between PERM-treated rats and controls. Further in vitro antimicrobial experiments were conducted to establish the antibacterial activity of PERM against different strains to obtain Minimal Inhibitory Concentrations. The main finding focused on the reduced abundance of Bacteroides-Prevotella-Porphyromonas species, increased Enterobacteriaceae and Lactobacillus in PERM-treated rats compared to controls. Changes of acetic and propionic acid levels were registered in PERM-treated group. From in vitro studies, PERM showed higher antibacterial activity against beneficial bacteria such as Bifidobacterium and Lactobacillus paracasei, while to inhibit potential pathogens as Staphylococcus aureus and Escherichia coli PERM concentration needed to be increased. In summary, exposure to PERM could affect the fecal microbiota and could be a crucial factor contributing to the development of diseases.

  18. Expression and function of Oat1 and Oat3 in rat kidney exposed to mercuric chloride

    Energy Technology Data Exchange (ETDEWEB)

    Di Giusto, Gisela; Torres, Adriana M. [Universidad Nacional de Rosario, CONICET, Area Farmacologia, Facultad de Ciencias Bioquimicas y Farmaceuticas, Rosario (Argentina); Anzai, Naohiko; Endou, Hitoshi [Kyorin University School of Medicine, Department of Pharmacology and Toxicology, Tokyo (Japan); Ruiz, Maria L. [Universidad Nacional de Rosario, CONICET, Instituto de Fisiologia Experimental, Facultad de Ciencias Bioquimicas y Farmaceuticas, Rosario (Argentina)

    2009-10-15

    This study was designed to evaluate the expression and function of the organic anion transporters, Oat1 and Oat3, in rats exposed to a nephrotoxic dose of HgCl{sub 2}. Oat1 protein expression increased in renal homogenates and decreased in renal basolateral membranes from HgCl{sub 2} rats, while Oat3 protein abundance decreased in both kidney homogenates and basolateral membranes. The lower protein levels of Oat1 and Oat3 in basolateral membranes explain the lower uptake capacity for p-aminohippurate (in vitro assays) and the diminution of the systemic clearance of this organic anion (in vivo studies) observed in treated rats. Since both transporters mediate mercury access to the renal cells, their down-regulation in basolateral membranes might be a defensive mechanism developed by the cell to protect itself against mercury injury. The pharmacological modulation of the expression and/or the function of Oat1 and Oat3 might be an effective therapeutic strategy for reducing the nephrotoxicity of mercury. (orig.)

  19. Activity of selected antioxidative enzymes in rats exposed to dimethoate and pyrantel tartrate.

    Science.gov (United States)

    Barski, D; Spodniewska, A

    2012-01-01

    This study presents the results of research concerning the effect of single and combined application of pyrantel tartrate and dimethoate on selected antioxidative enzymes: catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), in rat erythrocytes. Pyrantel tartrate was applied twice, at a dose of 85 mg/kg bw at a two week interval, i.e. on day 14 and 28 of the experiment, orally, in a water solution with a stomach tube. Dimethoate was administered with drinking water for 28 days at a dose of 25 mg/kg bw/day. It was found that pyrantel tartrate caused only small changes in the activity of the antioxidative enzymes under analysis. Subchronic exposure of rats to dimethoate caused a significant increase in the activity of CAT, SOD and GPx in erythrocytes, indicating the existence of strong oxidative stress. In combined intoxication, no significant effects of administering pyrantel tartrate on the activity of CAT, SOD and GPx was found in animals poisoned with dimethoate. The profile of changes was similar to that observed in rats exposed only to the organophosphorus insecticide. This may indicate a lack of interaction between the compounds used in the experiment.

  20. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas-González, Mariana C.; Del Razo, Luz M. [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); Barrera-Chimal, Jonatan [Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D. F., México (Mexico); Jacobo-Estrada, Tania [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); López-Bayghen, Esther [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); and others

    2013-11-01

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels.

  1. Mass spectrometry imaging of rat brain lipid profile changes over time following traumatic brain injury.

    Science.gov (United States)

    Roux, Aurelie; Muller, Ludovic; Jackson, Shelley N; Post, Jeremy; Baldwin, Katherine; Hoffer, Barry; Balaban, Carey D; Barbacci, Damon; Schultz, J Albert; Gouty, Shawn; Cox, Brian M; Woods, Amina S

    2016-10-15

    Mild traumatic brain injury (TBI) is a common public health issue that may contribute to chronic degenerative disorders. Membrane lipids play a key role in tissue responses to injury, both as cell signals and as components of membrane structure and cell signaling. This study demonstrates the ability of high resolution mass spectrometry imaging (MSI) to assess sequences of responses of lipid species in a rat controlled cortical impact model for concussion. A matrix of implanted silver nanoparticles was implanted superficially in brain sections for matrix-assisted laser desorption (MALDI) imaging of 50μm diameter microdomains across unfixed cryostat sections of rat brain. Ion-mobility time-of-flight MS was used to analyze and map changes over time in brain lipid composition in a rats after Controlled Cortical Impact (CCI) TBI. Brain MS images showed changes in sphingolipids near the CCI site, including increased ceramides and decreased sphingomyelins, accompanied by changes in glycerophospholipids and cholesterol derivatives. The kinetics differed for each lipid class; for example ceramides increased as early as 1 day after the injury whereas other lipids changes occurred between 3 and 7 days post injury. Silver nanoparticles MALDI matrix is a sensitive new tool for revealing previously undetectable cellular injury response and remodeling in neural, glial and vascular structure of the brain. Lipid biochemical and structural changes after TBI could help highlighting molecules that can be used to determine the severity of such injuries as well as to evaluate the efficacy of potential treatments. Copyright © 2016. Published by Elsevier B.V.

  2. The reduced cochlear output and the failure to adapt the central auditory response causes tinnitus in noise exposed rats.

    Directory of Open Access Journals (Sweden)

    Lukas Rüttiger

    Full Text Available Tinnitus is proposed to be caused by decreased central input from the cochlea, followed by increased spontaneous and evoked subcortical activity that is interpreted as compensation for increased responsiveness of central auditory circuits. We compared equally noise exposed rats separated into groups with and without tinnitus for differences in brain responsiveness relative to the degree of deafferentation in the periphery. We analyzed (1 the number of CtBP2/RIBEYE-positive particles in ribbon synapses of the inner hair cell (IHC as a measure for deafferentation; (2 the fine structure of the amplitudes of auditory brainstem responses (ABR reflecting differences in sound responses following decreased auditory nerve activity and (3 the expression of the activity-regulated gene Arc in the auditory cortex (AC to identify long-lasting central activity following sensory deprivation. Following moderate trauma, 30% of animals exhibited tinnitus, similar to the tinnitus prevalence among hearing impaired humans. Although both tinnitus and no-tinnitus animals exhibited a reduced ABR wave I amplitude (generated by primary auditory nerve fibers, IHCs ribbon loss and high-frequency hearing impairment was more severe in tinnitus animals, associated with significantly reduced amplitudes of the more centrally generated wave IV and V and less intense staining of Arc mRNA and protein in the AC. The observed severe IHCs ribbon loss, the minimal restoration of ABR wave size, and reduced cortical Arc expression suggest that tinnitus is linked to a failure to adapt central circuits to reduced cochlear input.

  3. Oral Administration of Ganoderma lucidum to Lead-Exposed Rats Protects Erythrocytes against Hemolysis: Implicates to Anti-Anemia

    Science.gov (United States)

    Hossain, Shahdat; Bhowmick, Sujan; Islam, Saiful; Rozario, Liza; Jahan, Sabrin; Hassan, Mehedi; Sarkar, Marzan; Choudhury, Bazlul Karim; Ahmed, Sohel; Shahjalal, Hussain

    2015-01-01

    We studied the effect of chronic oral exposure to lead acetate (PbA) on the sensitivity of RBC to hemolysis and whether the sensitivity could be decreased by feeding the rats with extract of medicinal mushroom Ganoderma lucidum. Three groups of rats, control, PbA-exposed, and G. lucidum (Gl)+PbA, were used. PbA (3 mM) was administered via drinking water and G. lucidum extract by gavage at 300 mg/Kg BW/day for 12 weeks. Afterwards, the rats were killed and washed RBCs were subjected to hemolysis in the presence of Fenton's reagents. Hemolysis was determined by estimating the amount of released hemoglobin. The levels of lipid peroxide (LPO) and GSH were determined from RBC membranes and whole RBCs, respectively. The levels of TNFα and LPO also were determined from hepatic tissues. The RBCs of PbA-exposed rats displayed significantly higher sensitivity to hemolysis than those of the Gl+PbA rats. The levels of LPO increased and GSH decreased in the RBCs, with concomitant increases in the levels of hepatic TNFα and LPO in the PbA-exposed rats. The degree of hemolysis was significantly low in the RBCs of Gl+PbA rats, concurrently with amelioration of hepatic parameters. Finally, the study suggests that PbA-induced-hemolysis and related oxidative-toxicity might be minimized by consumption of G. lucidum. PMID:26300947

  4. Oral Administration of Ganoderma lucidum to Lead-Exposed Rats Protects Erythrocytes against Hemolysis: Implicates to Anti-Anemia

    Directory of Open Access Journals (Sweden)

    Shahdat Hossain

    2015-01-01

    Full Text Available We studied the effect of chronic oral exposure to lead acetate (PbA on the sensitivity of RBC to hemolysis and whether the sensitivity could be decreased by feeding the rats with extract of medicinal mushroom Ganoderma lucidum. Three groups of rats, control, PbA-exposed, and G. lucidum (Gl+PbA, were used. PbA (3 mM was administered via drinking water and G. lucidum extract by gavage at 300 mg/Kg BW/day for 12 weeks. Afterwards, the rats were killed and washed RBCs were subjected to hemolysis in the presence of Fenton’s reagents. Hemolysis was determined by estimating the amount of released hemoglobin. The levels of lipid peroxide (LPO and GSH were determined from RBC membranes and whole RBCs, respectively. The levels of TNFα and LPO also were determined from hepatic tissues. The RBCs of PbA-exposed rats displayed significantly higher sensitivity to hemolysis than those of the Gl+PbA rats. The levels of LPO increased and GSH decreased in the RBCs, with concomitant increases in the levels of hepatic TNFα and LPO in the PbA-exposed rats. The degree of hemolysis was significantly low in the RBCs of Gl+PbA rats, concurrently with amelioration of hepatic parameters. Finally, the study suggests that PbA-induced-hemolysis and related oxidative-toxicity might be minimized by consumption of G. lucidum.

  5. Changes in the antioxidant defence and in selenium concentration in tissues of vanadium exposed rats.

    Science.gov (United States)

    Sanchez-Gonzalez, Cristina; Bermudez-Peña, Carmen; Trenzado, Cristina E; Goenaga-Infante, Heidi; Montes-Bayon, María; Sanz-Medel, Alfredo; Llopis, Juan

    2012-08-01

    Vanadium is an element whose role as a micronutrient for humans is not yet completely established, but which has been shown to possess hypoglycaemic properties in diabetes. In an earlier study, we showed that in STZ-diabetic rats, exposure to 1 mg V per day has no effect on glycaemia or on antioxidant status. When the exposure was raised to 3 mg V per day there was a hypoglycaemic effect, together with reduced Se in the tissues, which reduced antioxidant defences. The aim of the present study was to examine whether exposure to 1 mg V per day modifies Se nutritional status and/or antioxidant defences in healthy rats. Two groups of rats were examined: control and vanadium-treated. Vanadium, as bis(maltolato)oxovanadium(iv), was supplied in the drinking water. The experiment had a duration of five weeks. Selenium was measured in excreta, serum, skeletal muscle, kidneys, liver, heart, femur and adipose tissue. Number of red (RBC) and white (WBC) blood cells and haemoglobin (Hb) were determined in samples of whole blood. Glutathione peroxidase (GPx), glutathione transferase (GST), catalase (CAT) and NAD(P)H:quinine-oxidoreductase1 (NQO1) activity, and malondialdehyde (MDA) in the liver were evaluated. Treatment significantly reduced food intake, produced an anaemic state, and decreased Se absorption and Se content in serum, kidneys and the liver. GPx, GST and NQO1 activity were decreased in the liver, while MDA levels rose. We conclude that healthy rats are more sensitive than diabetic ones to the effects of V. This should be taken into account for populations that are particularly exposed to V for environmental reasons, and/or that consume V as a nutritional supplement.

  6. Astroglial Plasticity Is Implicated in Hippocampal Remodelling in Adult Rats Exposed to Antenatal Dexamethasone.

    Science.gov (United States)

    Shende, Vishvesh H; McArthur, Simon; Gillies, Glenda E; Opacka-Juffry, Jolanta

    2015-01-01

    The long-term effects of antenatal dexamethasone treatment on brain remodelling in 3-month-old male Sprague Dawley rats whose mothers had been treated with dexamethasone were investigated in the present study. Dorsal hippocampus, basolateral amygdala and nucleus accumbens volume, cell numbers, and GFAP-immunoreactive astroglial cell morphology were analysed using stereology. Total brain volume as assessed by micro-CT was not affected by the treatment. The relative volume of the dorsal hippocampus (% of total brain volume) showed a moderate, by 8%, but significant reduction in dexamethasone-treated versus control animals. Dexamethasone had no effect on the total and GFAP-positive cell numbers in the hippocampal subregions, basolateral amygdala, and nucleus accumbens. Morphological analysis indicated that numbers of astroglial primary processes were not affected in any of the hippocampal subregions analysed but significant reductions in the total primary process length were observed in CA1 by 32%, CA3 by 50%, and DG by 25%. Mean primary process length values were also significantly decreased in CA1 by 25%, CA3 by 45%, and DG by 25%. No significant astroglial morphological changes were found in basolateral amygdala and nucleus accumbens. We propose that the dexamethasone-dependent impoverishment of hippocampal astroglial morphology is the case of maladaptive glial plasticity induced prenatally.

  7. Astroglial Plasticity Is Implicated in Hippocampal Remodelling in Adult Rats Exposed to Antenatal Dexamethasone

    Directory of Open Access Journals (Sweden)

    Vishvesh H. Shende

    2015-01-01

    Full Text Available The long-term effects of antenatal dexamethasone treatment on brain remodelling in 3-month-old male Sprague Dawley rats whose mothers had been treated with dexamethasone were investigated in the present study. Dorsal hippocampus, basolateral amygdala and nucleus accumbens volume, cell numbers, and GFAP-immunoreactive astroglial cell morphology were analysed using stereology. Total brain volume as assessed by micro-CT was not affected by the treatment. The relative volume of the dorsal hippocampus (% of total brain volume showed a moderate, by 8%, but significant reduction in dexamethasone-treated versus control animals. Dexamethasone had no effect on the total and GFAP-positive cell numbers in the hippocampal subregions, basolateral amygdala, and nucleus accumbens. Morphological analysis indicated that numbers of astroglial primary processes were not affected in any of the hippocampal subregions analysed but significant reductions in the total primary process length were observed in CA1 by 32%, CA3 by 50%, and DG by 25%. Mean primary process length values were also significantly decreased in CA1 by 25%, CA3 by 45%, and DG by 25%. No significant astroglial morphological changes were found in basolateral amygdala and nucleus accumbens. We propose that the dexamethasone-dependent impoverishment of hippocampal astroglial morphology is the case of maladaptive glial plasticity induced prenatally.

  8. Impaired brain StAR and HSP70 gene expression in zebrafish exposed to Methyl-Parathion based insecticide.

    Science.gov (United States)

    da Rosa, João Gabriel Santos; Koakoski, Gessi; Piato, Angelo L; Bogo, Maurício Reis; Bonan, Carla Denise; Barcellos, Leonardo José Gil

    2016-01-01

    Fish production ponds and natural water body areas located in close proximity to agricultural fields receive water with variable amounts of agrochemicals, and consequently, compounds that produce adverse effects may reach nontarget organisms. The aim of this study was to investigate whether waterborne methyl-parathion-based insecticide (MPBI) affected gene expression patterns of brain glucocorticoid receptor (GR), steroidogenic acute regulatory protein (StAR), and heat shock protein 70 (hsp70) in adult zebrafish (Danio rerio) exposed to this chemical for 96 h. Treated fish exposed to MPBI-contaminated water showed an inhibition of brain StAR and hsp70 gene expression. Data demonstrated that MPBI produced a decrease brain StAR and hsp70 gene expression.

  9. 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.

  10. Gene Expression Profiling during Pregnancy in Rat Brain Tissue.

    Science.gov (United States)

    Mann, Phyllis E

    2014-03-04

    The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases "expectant brain" and "maternal brain". Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH) during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array) was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1) whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

  11. 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.

  12. Measurement of tritiated norepinephrine metabolism in intact rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Levitt, M.; Kowalik, S.; Barkai, A.I. (New York State Psychiatric Inst., New York (USA))

    1983-06-01

    A procedure for the study of NE metabolism in the intact rat brain is described. The method involves ventriculocisternal perfusion of the adult male rat with artificial CSF containing (/sup 3/H)NE. Radioactivity in the perfusate associated with NE and its metabolites 3,4-dihydroxymandelic acid (DOMA), 3,4-dihydroxphenylethyleneglycol (DHPG), 3-methoxy-4-hydroxymandelic acid (VMA), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), and normetanephrine (NMN) is separated using high-performance liquid chromatography (HPLC). After 80 min the radioactivity in the perfusate reaches an apparent steady-state. Analysis of the steady-state samples shows higher activity in the fractions corresponding to DHPG and MHPG than in those corresponding to DOMA and VMA, confirming glycol formation as the major pathway of NE metabolism in the rat brain. Pretreatment with an MAO inhibitor (tranylcypromine) results in a marked decrease in the deaminated metabolites DHPG and MHPG and a concurrent increase in NMN. The results indicate this to be a sensitive procedure for the in vivo determination of changes in NE metabolism.

  13. 7,8-Dihydroxyflavone, a Tropomyosin-Kinase Related Receptor B Agonist, Produces Fast-Onset Antidepressant-Like Effects in Rats Exposed to Chronic Mild Stress

    Science.gov (United States)

    Chang, Hsin-An; Wang, Ying-Hsiu; Tung, Che-Se; Yeh, Chin-Bin

    2016-01-01

    Objective Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), play important roles in treating depression. In this experiment, we examined whether 7,8-dihydroxyflavone, a novel potent TrkB agonist, could reverse the behavioral and biochemical abnormalities induced by the chronic mild stress (CMS) paradigm in rats. Methods SD rats were exposed to a battery of stressors for 56 days. 7,8-dihydroxyflavone (5 and 20 mg/kg) were administered intraperitoneally during the last 28 days of the CMS paradigm. Rats were tested in sucrose consumption test (SCT), forced-swimming test (FST) and elevated T-maze (ETM). Serum corticosterone levels and hippocampal BDNF levels of the rats were measured. Results Four-week CMS on the rats induced their depression-like behavior in SCT. The CMS-reduced sucrose consumption was reversed starting from 7 days after the 7,8-dihydroxyflavone (20 mg/kg) treatment and remained across the subsequent treatment regime. 7,8-dihydroxyflavone, when given at 5 mg/kg for 3 weeks, reduced the immobility time in the FST in the CMS-subjected rats. Additionally, the 4-week treatment with 7,8-dihydroxyflavone (20 mg/kg) attenuated the CMS-induced increase in anxiety-like behavior in the ETM. For the CMS-subjected rats, 7,8-dihydroxyflavone treatment dose-dependently reduced their serum corticosterone levels but increased their hippocampal BDNF levels only at 5 mg/kg. Conclusion 7,8-dihydroxyflavone was beneficial for both depression and anxiety-like behaviors, and may exert fast-onset antidepressant effects. This provides a new insight into the pharmacological management of depression.

  14. Effect of administration of vitamins C and E on fertilization capacity of rats exposed to noise stress

    Directory of Open Access Journals (Sweden)

    Ghasem Saki

    2013-01-01

    Full Text Available The aims of this study were to evaluate the effects of administration of Vitamins C and E on fertilization capacity in rats exposed to noise stress. 40 adult male rats were randomly divided into 5 equal groups. Group 1 as controls who were not exposed to noise and groups 2-5 exposed to noise with 90-120 dB intensity and 300-350 Hz frequency from 7 pm to 7 am everyday for 50 days. Group 2 exposed to noise and did not receive Vitamins. Group 3 received vitamin C, Group 4 received Vitamin E. Group 5 received Vitamins C and E concomitantly. After 50 days, serum Follicle-stimulating hormone (FSH, Luteinizing hormone (LH and testosterone were calculated. Then each rat was left with three female rats for mating. Pregnant females were sacrificed on the 19 th day of pregnancy and evaluated for the presence and number of viable, dead and absorbed fetuses. The level of FSH, LH and testosterone significantly decreased in rats exposed to noise (P < 0.05. By administration of Vitamins in groups 3-5 we observed that the level of hormones significantly increased in compared to group 2 (P < 0.05. The fertilization capacity of male rats in groups 3-5 significantly increased in compared to group 2 (P < 0.05. There was significant difference between groups 1 and 2 in case of fertilization capacity (P = 0.001. The data in this study strongly suggests a negative role for noise stress on level of FSH, LH and testosterone level and also fertilization capacity of male rats. To complement the information it is suggested that this research be done on human samples.

  15. 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

  16. [An immunocytochemical study of the C-cell function of the thyroid in rats exposed on the Kosmos-2044 biosatellite].

    Science.gov (United States)

    Loginov, V I

    1993-01-01

    Immunocytochemical analysis of thyroid gland C-cells of the rats exposed to a 14-day space flight revealed a decrease in the number of C-cells, volume of their nuclei and a declined percentage of active secretory C-cells, which point to a decline of calcitonin proactive and calcitonin secretory hypofunction of the thyroid C-cells system in flown rats. Tail suspension as a microgravity model caused similar changes in C-cells.

  17. Impact of Inhaled Nitric Oxide on the Sulfatide Profile of Neonatal Rat Brain Studied by TOF-SIMS Imaging

    Directory of Open Access Journals (Sweden)

    Hanane Kadar

    2014-03-01

    Full Text Available Despite advances in neonatal intensive care leading to an increased survival rate in preterm infants, brain lesions and subsequent neurological handicaps following preterm birth remain a critical issue. To prevent brain injury and/or enhance repair, one of the most promising therapies investigated in preclinical models is inhaled nitric oxide (iNO. We have assessed the effect of this therapy on brain lipid content in air- and iNO-exposed rat pups by mass spectrometry imaging using a time-of-flight secondary ion mass spectrometry (TOF-SIMS method. This technique was used to map the variations in lipid composition of the rat brain and, particularly, of the white matter. Triplicate analysis showed a significant increase of sulfatides (25%–50% in the white matter on Day 10 of life in iNO-exposed animals from Day 0–7 of life. These robust, repeatable and semi-quantitative data demonstrate a potent effect of iNO at the molecular level.

  18. Proteomic analysis of hippocampal proteins of F344 rats exposed to 1-bromopropane.

    Science.gov (United States)

    Huang, Zhenlie; Ichihara, Sahoko; Oikawa, Shinji; Chang, Jie; Zhang, Lingyi; Takahashi, Masahide; Subramanian, Kaviarasan; Mohideen, Sahabudeen Sheik; Wang, Yun; Ichihara, Gaku

    2011-11-15

    1-Bromopropane (1-BP) is a compound used as an alternative to ozone-depleting solvents and is neurotoxic both in experimental animals and human. However, the molecular mechanisms of the neurotoxic effects of 1-BP are not well known. To identify the molecular mechanisms of 1-BP-induced neurotoxicity, we analyzed quantitatively changes in protein expression in the hippocampus of rats exposed to 1-BP. Male F344 rats were exposed to 1-BP at 0, 400, or 1000 ppm for 8h/day for 1 or 4 weeks by inhalation. Two-dimensional difference in gel electrophoresis (2D-DIGE) combined with matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) were conducted to detect and identify protein modification. Changes in selected proteins were further confirmed by western blot. 2D-DIGE identified 26 proteins with consistently altered model (increase or decrease after both 1- and 4-week 1-BP exposures) and significant changes in their levels (p<0.05; fold change ≥ ± 1.2) at least at one exposure level or more compared with the corresponding controls. Of these proteins, 19 were identified by MALDI-TOF-TOF/MS. Linear regression analysis of 1-BP exposure level identified 8 differentially expressed proteins altered in a dose-dependent manner both in 1- and 4-week exposure experiments. The identified proteins could be categorized into diverse functional classes such as nucleocytoplasmic transport, immunity and defense, energy metabolism, ubiquitination-proteasome pathway, neurotransmitter and purine metabolism. Overall, the results suggest that 1-BP-induced hippocampal damage involves oxidative stress, loss of ATP production, neurotransmitter dysfunction and inhibition of ubiquitination-proteasome system.

  19. 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.

  20. 高压氧对脑损伤大鼠BDNF表达的影响%Effects of hyperbaric oxygen therapy on the expression level of brain-derived neurotrophic factor after traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    张禹; 潘树义; 李航; 杨晨; 潘晓雯

    2012-01-01

    Objective To observe the effect of hyperbaric oxygen (HBO) treatment on the expression of brain-derived neu rotrophic factor (BDNF) in cerebral cortex and hippocampus of adult rats with lateral fluid percussion attack. Methods Thir ty-two male Wistar rats were divided into brain-injured group and control group with 16 rats in each group. Lateral brain injury model was established in the brain-injured group by fluid percussion attack machine and those rats were divided into two subgroups to be exposed in HBO and nonpressurized air respectively with eight rats in each subgroup. Heads were cut and brains were taken after five days. The morphological changes in cerebral cortex and hippocampus of the brain specimens were observed with electron microscope and the expressions of BDNF were detected with immunohistochemistry. Results There was no significant difference in the number of BDNF positive cells among each normal control groups (P > 0.05). But there were more BDNF positive cells in HBO exposed injury group than that in nonpressurized air exposed group (P 0.05);脑损伤组中HBO暴露后皮层及海马BDNF免疫阳性细胞数多于常压空气暴露(P < 0.01),脑损伤常压空气暴露组多于正常对照常压空气暴露组(P < 0.01).结论 大鼠脑损伤后可以提高损伤皮层及海马区BDNF的表达,HBO治疗可以进一步提高大鼠脑内BNDF的表达.

  1. Parallel assessment of male reproductive function in workers and wild rats exposed to pesticides in banana plantations in Guadeloupe.

    Science.gov (United States)

    Multigner, Luc; Kadhel, Philippe; Pascal, Michel; Huc-Terki, Farida; Kercret, Henri; Massart, Catherine; Janky, Eustase; Auger, Jacques; Jégou, Bernard

    2008-07-30

    There is increasing evidence that reproductive abnormalities are increasing in frequency in both human population and among wild fauna. This increase is probably related to exposure to toxic contaminants in the environment. The use of sentinel species to raise alarms relating to human reproductive health has been strongly recommended. However, no simultaneous studies at the same site have been carried out in recent decades to evaluate the utility of wild animals for monitoring human reproductive disorders. We carried out a joint study in Guadeloupe assessing the reproductive function of workers exposed to pesticides in banana plantations and of male wild rats living in these plantations. A cross-sectional study was performed to assess semen quality and reproductive hormones in banana workers and in men working in non-agricultural sectors. These reproductive parameters were also assessed in wild rats captured in the plantations and were compared with those in rats from areas not directly polluted by humans. No significant difference in sperm characteristics and/or hormones was found between workers exposed and not exposed to pesticide. By contrast, rats captured in the banana plantations had lower testosterone levels and gonadosomatic indices than control rats. Wild rats seem to be more sensitive than humans to the effects of pesticide exposure on reproductive health. We conclude that the concept of sentinel species must be carefully validated as the actual nature of exposure may varies between human and wild species as well as the vulnerable time period of exposure and various ecological factors.

  2. Intranasal pyrrolidine dithiocarbamate decreases brain inflammatory mediators and provides neuroprotection after brain hypoxia-ischemia in neonatal rats.

    Science.gov (United States)

    Wang, Zhi; Zhao, Huijuan; Peng, Shuling; Zuo, Zhiyi

    2013-11-01

    Brain injury due to birth asphyxia is the major cause of death and long-term disabilities in newborns. We determined whether intranasal pyrrolidine dithiocarbamate (PDTC) could provide neuroprotection in neonatal rats after brain hypoxia-ischemia (HI). Seven-day old male and female Sprague-Dawley rats were subjected to brain HI. They were then treated with intranasal PDTC. Neurological outcomes were evaluated 7 or 30 days after the brain HI. Brain tissues were harvested 6 or 24 h after the brain HI for biochemical analysis. Here, PDTC dose-dependently reduced brain HI-induced brain tissue loss with an effective dose (ED)50 at 27 mg/kg. PDTC needed to be applied within 45 min after the brain HI for this neuroprotection. This treatment reduced brain tissue loss and improved neurological and cognitive functions assessed 30 days after the HI. PDTC attenuated brain HI-induced lipid oxidative stress, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells, and various inflammatory mediators in the brain tissues. Inhibition of inducible nitric oxide synthase after brain HI reduced brain tissue loss. Our results suggest that intranasal PDTC provides neuroprotection possibly via reducing inflammation and oxidative stress. Intranasal PDTC may have a potential to provide neuroprotection to human neonates after birth asphyxia.

  3. Effect of dehydroepiandrosterone (DHEA) on memory and brain derived neurotrophic factor (BDNF) in a rat model of vascular dementia.

    Science.gov (United States)

    Sakr, H F; Khalil, K I; Hussein, A M; Zaki, M S A; Eid, R A; Alkhateeb, M

    2014-02-01

    The effect of dehydroepiandrosterone (DHEA) on memory and cognition in experimental animals is well known, but its efficacy in clinical dementia is unproven. So, the aim of the present study was to investigate the effect of DHEA on learning and memory activities in a rat model of vascular dementia (VD). Forty-eight male rats that positively passed the holeboard memory test were chosen for the study before bilateral permanent occlusion of the common carotid artery. They were divided into four groups (n=12, each) as follows (i) untreated control, (ii) rats exposed to surgical permanent bilateral occlusion of the common carotid arteries (BCCAO) leading to chronic cerebral hypoperfusion, (iii) rats exposed to BCCAO then received DHEA (BCCAO + DHEA) and (i.v.) rats exposed to BCCAO then received donepezil (BCCAO + DON). Holeboard memory test was used to assess the time, latency, working memory and reference memory. Central level of acetylcholine, norepinephrine and dopamine in the hippocampus were measured. Furthermore, the expression of brain derived neurotrophic factor (BDNF) in the hippocampus was determined. Histopathological studies of the cerebral cortex and transmission electron microscope of the hippocampus were performed. BCCAO decreased the learning and memory activities in the holeboard memory. Also, it decreased the expression of BDNF as well as the central level of acetylcholine, noradrenaline and dopamine as compared to control rats. Treatment with DHEA and donepezil increased the working and reference memories, BDNF expression as well as the central acetylcholine in the hippocampus as compared to BCCAO rats. DHEA produced neuroprotective effects through increasing the expression of BDNF as well as increasing the central level of acetylcholine and catecholamines which are non-comparable to donepezil effects.

  4. [Effects of carbocisteine on airway inflammation and related events in SO2-exposed rats].

    Science.gov (United States)

    Ishibashi, Y; Okamura, T; Masumoto, Y; Tachiiri, T; Momo, K

    2001-01-01

    Airway inflammation leads to secretion of abnormal mucous glycoprotein and ciliary injury. To investigate the possible usefulness of carbocisteine against airway inflammation and events related to it, we conducted a study in SO2-exposed rats of the effects of carbocisteine and ambroxol, as an active control drug, on components of mucous glycoprotein (fucose, sialic acid and protein) in bronchoalveolar lavage fluid (BALF); on infiltration and activation of inflammatory cells in BALF; on tracheal and bronchial-ciliary lesions; and on cAMP levels in tracheal and alveolar tissues. Carbocisteine inhibited or improved all SO2-induced changes tested, and dosages of 125 and 250 mg/kg b.i.d. reduced fucose, sialic acid and protein contents, inflammatory cells (as markers of inflammation), free radicals, and elastase activity in BALF, and suppressed the development of ciliary lesions of the tracheal and bronchial mucosa, while ambroxol (10 mg/kg b.i.d.) showed no such effects. In addition, carbocisteine improved cAMP levels in the tracheal and alveolar tissues. These results indicate that carbocisteine is able to prevent the development of inflammation-related respiratory disease in this rat model, and that this remission of airway inflammation may be associated with carbocisteine-induced normalization of cAMP levels in tracheal and alveolar tissues as well as with its mucoregulant and anti-inflammatory effects. In conclusion, carbocisteine has a unique mucoregulant action and inhibits SO2-induced airway inflammation in a manner different from that of ambroxol.

  5. Induction of a heat shock response (HSP 72) in rat embryos exposed to selected chemical teratogens.

    Science.gov (United States)

    Mirkes, P E; Doggett, B; Cornel, L

    1994-02-01

    A monoclonal antibody to the 72 kD heat shock protein (HSP 72), Western blot analysis and 2-D gel electrophoresis/autoradiography were used to determine whether selected chemical teratogens induced the synthesis and accumulation of HSP 72 in postimplantation rat embryos exposed in vitro. The chemical teratogens studied include N-Acetoxy-2-acetylaminofluorene (N-Ac-AAF), cadmium chloride (CAD), cyclophosphamide (CP), sodium arsenite (AS), and sodium salicylate (SAL). Exposures to test chemicals were selected that produced obvious embryotoxicity characterized by abnormal development and growth retardation. Of the five chemical teratogens studied, AS and SAL induced the synthesis and accumulation of HSP 72 in day 10 rat embryos. The kinetics of HSP 72 accumulation, however, differed between AS- and SAL-treated embryos. Maximal levels of HSP 72 were observed 24 hours after AS exposure and 10 hours after SAL exposure. N-Ac-AAF, CD, and CP induced obvious embryotoxicity; however, none of these chemical teratogens induced HSP 72 at any of the timepoints assayed. Although only a small sample of chemical teratogens was studied, our results suggest that the heat shock response, characterized by the synthesis and accumulation of HSP 72, is not a general biomarker for chemical teratogens.

  6. Hydrogen Sulfide Ameliorates Early Brain Injury Following Subarachnoid Hemorrhage in Rats.

    Science.gov (United States)

    Cui, Yonghua; Duan, Xiaochun; Li, Haiying; Dang, Baoqi; Yin, Jia; Wang, Yang; Gao, Anju; Yu, Zhengquan; Chen, Gang

    2016-08-01

    Increasing studies have demonstrated the neuroprotective effect of hydrogen sulfide (H2S) in central nervous system (CNS) diseases. However, the potential application value of H2S in the therapy of subarachnoid hemorrhage (SAH) is still not well known. This study was to investigate the potential effect of H2S on early brain injury (EBI) induced by SAH and explore the underlying mechanisms. The role of sodium hydrosulfide (NaHS), a donor of H2S, in SAH-induced EBI, was investigated in both in vivo and in vitro. A prechiasmatic cistern single injection model was used to produce experimental SAH in vivo. In vitro, cultured primary rat cortical neurons and human umbilical vein endothelial cells (HUVECs) were exposed to OxyHb at concentration of 10 μM to mimic SAH. Endogenous production of H2S in the brain was significantly inhibited by SAH. The protein levels of the predominant H2S-generating enzymes in the brain, including cystathionineb-synthase (CBS) and 3-mercaptopyruvate sulfur transferase (3MST), were also correspondingly reduced by SAH, while treatment with NaHS restored H2S production and the expressions of CBS and 3MST. More importantly, NaHS treatment could significantly attenuate EBI (including brain edema, blood-brain barrier disruption, brain cell apoptosis, inflammatory response, and cerebral vasospasm) after SAH. In vitro, H2S protects neurons and endothelial function by functioning as an antioxidant and antiapoptotic mediator. Our results suggest that NaSH as an exogenous H2S donor could significantly reduce EBI induced by SAH.

  7. Early life stress-induced alterations in rat brain structures measured with high resolution MRI.

    Science.gov (United States)

    Sarabdjitsingh, R Angela; Loi, Manila; Joëls, Marian; Dijkhuizen, Rick M; van der Toorn, Annette

    2017-01-01

    Adverse experiences early in life impair cognitive function both in rodents and humans. In humans this increases the vulnerability to develop mental illnesses while in the rodent brain early life stress (ELS) abnormalities are associated with changes in synaptic plasticity, excitability and microstructure. Detailed information on the effects of ELS on rodent brain structural integrity at large and connectivity within the brain is currently lacking; this information is highly relevant for understanding the mechanism by which early life stress predisposes to mental illnesses. Here, we exposed rats to 24 hours of maternal deprivation (MD) at postnatal day 3, a paradigm known to increase corticosterone levels and thereby activate glucocorticoid receptors in the brain. Using structural magnetic resonance imaging we examined: i) volumetric changes and white/grey matter properties of the whole cerebrum and of specific brain areas; and ii) whether potential alterations could be normalized by blocking glucocorticoid receptors with mifepristone during the critical developmental window of early adolescence, i.e. between postnatal days 26 and 28. The results show that MD caused a volumetric reduction of the prefrontal cortex, particularly the ventromedial part, and the orbitofrontal cortex. Within the whole cerebrum, white (relative to grey) matter volume was decreased and region-specifically in prefrontal cortex and dorsomedial striatum following MD. A trend was found for the hippocampus. Grey matter fractions were not affected. Treatment with mifepristone did not normalize these changes. This study indicates that early life stress in rodents has long lasting consequences for the volume and structural integrity of the brain. However, changes were relatively modest and-unlike behavior- not mitigated by blockade of glucocorticoid receptors during a critical developmental period.

  8. Glutathione and glutathione-related enzymes in rats exposed to dimethoate and/or pyrantel.

    Science.gov (United States)

    Spodniewska, A

    2014-01-01

    The study was undertaken to examine the effect of single and combined administration of dimethoate (an OP insecticide) and pyrantel embonate (an anthelmintic agent) on the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx) and glutathione reductase (GR) in rats. Dimethoate (Group I) was administered to rats at a dose of 1/10 LD50 for 5 consecutive days and pyrantel embonate (Group II) at a dose of 1/5 LD50 for 3 consecutive days. The animals of group III were given both of the mentioned above compounds in the same manner as group I and II, but pyrantel embonate was applied on day 3, 4, and 5 from the beginning of dimethoate intoxication. Material from 6 rats randomly selected from each group was obtained after 3, 6 and 12 hours and 2, 7 and 14 days following the last applied dose of the compounds under study. It was found that application of pyrantel embonate caused only slight changes in the analysed parameters i.e. GSH, GPx and GR. Dimethoate administration caused disturbances in the antioxidative system manifested as a decrease in GSH concentration in the liver (max.--37.7% after 6 hours) and an increase of GPx and GR activities in erythrocytes (max.--21.7% and 29.6% after 3 hours, respectively), compared to the control group. The profile of changes after combined intoxication was similar, but their intensity was higher compared to the group of animals exposed to dimethoate only. Based on current studies, it was concluded that both dimethoate and pyrantel embonate at the applied doses showed a pro-oxidative activity.

  9. 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.

  10. Properties of Opiate-Receptor Binding in Rat Brain

    Science.gov (United States)

    Pert, Candace B.; Snyder, Solomon H.

    1973-01-01

    [3H]Naloxone, a potent opiate antagonist, binds stereospecifically to opiate-receptor sites in rat-brain tissue. The binding is time, temperature, and pH dependent and saturable with respect to [3H]naloxone and tissue concentration. The [3H]naloxone-receptor complex formation is bimolecular with a dissociation constant of 20 nM. 15 Opiate agonists and antagonists compete for the same receptors, whose density is 30 pmol/g. Potencies of opiates and their antagonists in displacing [3H]naloxone binding parallel their pharmacological potencies. PMID:4525427

  11. A simple implantation method for flexible, multisite microelectrodes into rat brains.

    Science.gov (United States)

    Richter, Anja; Xie, Yijing; Schumacher, Anett; Löffler, Susanne; Kirch, Robert D; Al-Hasani, Jaafar; Rapoport, Daniel H; Kruse, Charli; Moser, Andreas; Tronnier, Volker; Danner, Sandra; Hofmann, Ulrich G

    2013-01-01

    A long term functional and reliable coupling between neural tissue and implanted microelectrodes is the key issue in acquiring neural electrophysiological signals or therapeutically excite neural tissue. The currently often used rigid micro-electrodes are thought to cause a severe foreign body reaction resulting in a thick glial scar and consequently a poor tissue-electrode coupling in the chronic phase. We hypothesize, that this adverse effect might be remedied by probes compliant to the soft brain tissue, i.e., replacing rigid electrodes by flexible ones. Unfortunately, this flexibility comes at the price of a low stiffness, which makes targeted low trauma implantation very challenging. In this study, we demonstrate an adaptable and simple method to implant extremely flexible microprobes even to deep areas of rat's brain. Implantation of flexible probes is achieved by rod supported stereotactic insertion fostered by a hydrogel (2% agarose in PBS) cushion on the exposed skull. We were thus able to implant very flexible micro-probes in 70 rats as deep as the rodent's subthalamic nucleus. This work describes in detail the procedures and steps needed for minimal invasive, but reliable implantation of flexible probes.

  12. Effect of propofol in the immature rat brain on short- and long-term neurodevelopmental outcome.

    Directory of Open Access Journals (Sweden)

    Tanja Karen

    Full Text Available BACKGROUND: Propofol is commonly used as sedative in newborns and children. Recent experimental studies led to contradictory results, revealing neurodegenerative or neuroprotective properties of propofol on the developing brain. We investigated neurodevelopmental short- and long-term effects of neonatal propofol treatment. METHODS: 6-day-old Wistar rats (P6, randomised in two groups, received repeated intraperitoneal injections (0, 90, 180 min of 30 mg/kg propofol or normal saline and sacrificed 6, 12 and 24 hrs following the first injection. Cortical and thalamic areas were analysed by Western blot and quantitative real-time PCR (qRT-PCR for expression of apoptotic and neurotrophin-dependent signalling pathways. Long-term effects were assessed by Open-field and Novel-Object-Recognition at P30 and P120. RESULTS: Western blot analyses revealed a transient increase of activated caspase-3 in cortical, and a reduction of active mitogen-activated protein kinases (ERK1/2, AKT in cortical and thalamic areas. qRT-PCR analyses showed a down-regulation of neurotrophic factors (BDNF, NGF, NT-3 in cortical and thalamic regions. Minor impairment in locomotive activity was observed in propofol treated adolescent animals at P30. Memory or anxiety were not impaired at any time point. CONCLUSION: Exposing the neonatal rat brain to propofol induces acute neurotrophic imbalance and neuroapoptosis in a region- and time-specific manner and minor behavioural changes in adolescent animals.

  13. CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia.

    Science.gov (United States)

    Fiedorowicz, Michał; Makarewicz, Dorota; Stańczak-Mrozek, Kinga I; Grieb, Paweł

    2008-01-01

    To estimate protective potential of citicoline in a model of birth asphyxia, the drug was given to 7-day old rats subjected to permanent unilateral carotid artery occlusion and exposed for 65 min to a hypoxic gas mixture. Daily citicoline doses of 100 or 300 m/kg, or vehicle, were injected intraperitoneally for 7 consecutive days beginning immediately after the end of the ischemic-hypoxic insult, and brain damage was assessed by gross zorphology score and weight deficit two weeks after the insult. Caspase-3, alpha-fodrin, Bcl-2, and Hsp70 levels were assessed at 0, 1, and 24 h after the end of the hypoxic insult in another group of rat pups subjected to the same insult and given a single dose of 300 m/kg of citicoline or the vehicle. Citicoline markedly reduced caspase-3 activation and Hsp70 expression 24 h after the insult, and dose-dependently attenuated brain damage. In the context of the well-known excellent safety profile of citicoline, these data suggest that clinical evaluation of the efficacy of the drug in human birth asphyxia may be warranted.

  14. 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....

  15. Reduced Bone and Body Mass in Young Male Rats Exposed to Lead

    Directory of Open Access Journals (Sweden)

    Fellipe Augusto Tocchini de Figueiredo

    2014-01-01

    Full Text Available The aim of this study was to see whether there would be differences in whole blood versus tibia lead concentrations over time in growing rats prenatally. Lead was given in the drinking water at 30 mg/L from the time the dams were pregnant until offspring was 28- or 60-day-old. Concentrations of lead were measured in whole blood and in tibia after 28 (28D and 60 days (60D in control (C and in lead-exposed animals (Pb. Lead measurements were made by GF-AAS. There was no significant difference (P>0.05 in the concentration of whole blood lead between Pb-28D (8.0±1.1 μg/dL and Pb-60D (7.2±0.89 μg/dL, while both significantly varied (P<0.01 from controls (0.2 μg/dL. Bone lead concentrations significantly varied between the Pb-28D (8.02±1.12 μg/g and the Pb-60D (43.3±13.26 μg/g lead-exposed groups (P<0.01, while those exposed groups were also significantly higher (P<0.0001 than the 28D and 60D control groups (Pb < 1 μg/g. The Pb-60D group showed a 25% decrease in tibia mass as compared to the respective control. The five times higher amount of lead found in the bone of older animals (Pb-60D versus Pb-28D, which reinforces the importance of using bone lead as an exposure biomarker.

  16. Assessment of physical traits of rat offspring derived from mothers exposed to dioxin.

    Science.gov (United States)

    Rosińczuk, Joanna; Całkosiński, Ireneusz

    2015-09-01

    Negative effects of dioxin action are associated with limited abilities of their bio-degradation along with continuously increasing production and long-term bio-accumulation of those toxins in living organisms. Dioxins penetrate through placenta to fetus indicating indirect toxic effects on offspring of mothers exposed to the action of these toxins. During lactation a significant part of dioxins is excreted from organism with milk, which contributes to further accumulation of those compounds and multiple exceeding of maximal permissible dose of dioxins in newborns feeding with mother's milk. The aim of the study was to determine how a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administered to females 3 weeks before getting pregnant affects the parturition duration, labour delay, number and weight of offspring. The studies were performed on rat offspring deriving from primigravida females from the Buffalo strain, which 3 weeks before getting pregnant were administered with a single dose of TCDD. The obtained results revealed that labours in females exposed to dioxin effects were characterized by significant temporal range and their end occurred 3 weeks later compared to females from the control group, which gave birth within a very narrow temporal range ending within 2 days. Offspring obtained from females exposed to the TCDD action was smaller in number and was characterized by smaller rearing and smaller birth weight even after the first month of life; however weight gain in both groups was similar and it was twelve-fold increase. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. [The effect of ethanol consumption by dams on the offspring locomotion in the open field test and carboxypeptidase activities in the rat brain and adrenal medulla].

    Science.gov (United States)

    Mukhina, E S; Saldaev, D A; Vernigora, A N; Gengin, M T

    2005-03-01

    Consumption of dams ethanol increased the posterity locomotion activity in open field test. The increase in female rats was higher then in male ones. Differences in the carboxypeptidase H and PMSF-inhibited carboxypeptidase activities between the brain regions and adrenal medulla of prenatally exposed to ethanol and intact rats were found. The changing of enzyme activities in female rats was higher then in male ones. It is possible that dams ethanol consumption induced profound changes in locomotion mediated, at least partially, by changes in the rate of proteolytic processing of neuropeptide precursors.

  18. Neuronal reorganization in adult rats neonatally exposed to (±-3,4-methylenedioxymethamphetamine

    Directory of Open Access Journals (Sweden)

    Michael T. Williams

    2014-01-01

    Full Text Available The abuse of methylenedioxymethamphetamine (MDMA during pregnancy is of concern. MDMA treatment of rats during a period of brain growth analogous to late human gestation leads to neurochemical and behavioral changes. MDMA from postnatal day (P11–20 in rats produces reductions in serotonin and deficits in spatial and route-based navigation. In this experiment we examined the impact of MDMA from P11 to P20 (20 mg/kg twice daily, 8 h apart on neuronal architecture. Golgi impregnated sections showed significant changes. In the nucleus accumbens, the dendrites were shorter with fewer spines, whereas in the dentate gyrus the dendritic length was decreased but with more spines, and for the entorhinal cortex, reductions in basilar and apical dendritic lengths in MDMA animals compared with saline animals were seen. The data show that neuronal cytoarchitectural changes are long-lasting following developmental MDMA exposure and are in regions consistent with the learning and memory deficits observed in such animals.

  19. Proteomic analysis of hippocampal proteins of F344 rats exposed to 1-bromopropane

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenlie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Toxicology, Guangdong Prevention and Treatment Center for Occupational Diseases, Guangzhou 510-300 (China); Ichihara, Sahoko [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Chang, Jie [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Zhang, Lingyi [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Takahashi, Masahide [Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Subramanian, Kaviarasan; Mohideen, Sahabudeen Sheik [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Wang, Yun [Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ichihara, Gaku, E-mail: gak@med.nagoya-u.ac.jp [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan)

    2011-11-15

    1-Bromopropane (1-BP) is a compound used as an alternative to ozone-depleting solvents and is neurotoxic both in experimental animals and human. However, the molecular mechanisms of the neurotoxic effects of 1-BP are not well known. To identify the molecular mechanisms of 1-BP-induced neurotoxicity, we analyzed quantitatively changes in protein expression in the hippocampus of rats exposed to 1-BP. Male F344 rats were exposed to 1-BP at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks by inhalation. Two-dimensional difference in gel electrophoresis (2D-DIGE) combined with matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) were conducted to detect and identify protein modification. Changes in selected proteins were further confirmed by western blot. 2D-DIGE identified 26 proteins with consistently altered model (increase or decrease after both 1- and 4-week 1-BP exposures) and significant changes in their levels (p < 0.05; fold change {>=} {+-} 1.2) at least at one exposure level or more compared with the corresponding controls. Of these proteins, 19 were identified by MALDI-TOF-TOF/MS. Linear regression analysis of 1-BP exposure level identified 8 differentially expressed proteins altered in a dose-dependent manner both in 1- and 4-week exposure experiments. The identified proteins could be categorized into diverse functional classes such as nucleocytoplasmic transport, immunity and defense, energy metabolism, ubiquitination-proteasome pathway, neurotransmitter and purine metabolism. Overall, the results suggest that 1-BP-induced hippocampal damage involves oxidative stress, loss of ATP production, neurotransmitter dysfunction and inhibition of ubiquitination-proteasome system. -- Highlights: Black-Right-Pointing-Pointer 1-BP modified hippocampal proteome in rat and 19 altered proteins were identified. Black-Right-Pointing-Pointer Expression of Ran, TPI, HSP60, PSMA1, ECH1, TPI, B-CK and DJ-1 was changed by 1-BP. Black

  20. Alteration of brain levels of neurotransmitters and amino acids in male F344 rats induced by three-week repeated inhalation exposure to 1-bromopropane.

    Science.gov (United States)

    Suda, Megumi; Honma, Takeshi; Miyagawa, Muneyuki; Wang, Rui-Sheng

    2008-08-01

    The present study investigated the effects of 1-bromopropane (1BP) on brain neuroactive substances of rats to determine the extent of its toxicity to the central nervous system (CNS). We measured the changes in neurotransmitters (acetylcholine, catecholamine, serotonin and amino acids) and their metabolites or precursors in eight brain regions after inhalation exposure to 1BP at 50 to 1,000 ppm for 8 h per day for 7 d per week for 3 wk. Rats were sacrificed at 2 h (Case 1), or at 19 h (Case 2) after the end of exposure. In Case 1, the level of 5-hydroxyindoleacetic acid (5HIAA) was lowered in some brain regions by 1BP exposure. The decrease of 5HIAA in the frontal cortex was statistically significant at 50 ppm 1BP exposure. In Case 2, gamma-amino butyric acid (GABA) and taurine were decreased in many brain regions of exposed rats, and a significant decrease of taurine in the midbrain occurred at 50 ppm 1BP exposure. In both cases of 2-h and 19-h intervals from the end of exposure to sacrifice, aspartate and glutamine levels were elevated in many brain regions, but the acetylcholine level did not change in any brain region. Three-week repeated exposure to 1BP produced significantly changes in amino acid contents of rat brains, particularly at 1,000 ppm.

  1. Inulin supplementation during gestation mitigates acrylamide-induced maternal and fetal brain oxidative dysfunctions and neurotoxicity in rats.

    Science.gov (United States)

    Krishna, Gokul; Muralidhara

    2015-01-01

    Accumulating evidence suggests that the developing brain is more susceptible to a variety of chemicals. Recent studies have shown a link between the enteric microbiota and brain function. While supplementation of non-digestible oligosaccharides during pregnancy has been demonstrated to positively influence human health mediated through stimulation of beneficial microbiota, our understanding on their neuromodulatory propensity is limited. In the present study, our primary focus was to examine whether supplementation of inulin (a well known fructan) during gestation can abrogate acrylamide (ACR)-induced oxidative impairments and neurotoxicity in maternal and fetal brain of rats. Initially, in a dose-determinative study, we recapitulated the impact of ACR exposure during gestation days (GD 6-19) on gestational parameters, extent of oxidative impairments in brain (maternal/fetal), cholinergic function and neurotoxicity. Subsequently, pregnant rats orally (gavage) administered with inulin (IN, 2 g/kg/day in two equal installments) supplements during gestation days (GD 0-19) were exposed to ACR (200 ppm) in drinking water. IN supplements significantly attenuated ACR-induced changes in exploratory activity (reduced open field exploration) measured on GD 14. Further, IN restored the placental weights among ACR exposed dams. Analysis of biochemical markers revealed that IN supplements effectively offset ACR associated oxidative stress not only in the maternal brain, but in the fetal brain as well. Elevated levels of protein carbonyls in maternal brain regions were completely normalized with IN supplements. More importantly, IN supplements significantly augmented the number of Bifidobacteria in the cecum of ACR rats which correlated well with the neurorestorative effect as evidenced by restored dopamine levels in the maternal cortex and fetal brain acetylcholinesterase activity among ACR-exposed dams. Further, IN supplements also conferred significant protection against

  2. Neuroprotective effects of dexmedetomidine against hyperoxia-induced injury in the developing rat brain

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    Endesfelder, Stefanie; Makki, Hanan; von Haefen, Clarissa; Spies, Claudia D.; Bührer, Christoph; Sifringer, Marco

    2017-01-01

    Dexmedetomidine (DEX) is a highly selective agonist of α2-receptors with sedative, anxiolytic, and analgesic properties. Neuroprotective effects of dexmedetomidine have been reported in various brain injury models. In the present study, we investigated the effects of dexmedetomidine on hippocampal neurogenesis, specifically the proliferation capacity and maturation of neurons and neuronal plasticity following the induction of hyperoxia in neonatal rats. Six-day old sex-matched Wistar rats were exposed to 80% oxygen or room air for 24 h and treated with 1, 5 or 10 μg/kg of dexmedetomidine or normal saline. A single pretreatment with DEX attenuated the hyperoxia-induced injury in terms of neurogenesis and plasticity. In detail, both the proliferation capacity (PCNA+ cells) as well as the expression of neuronal markers (Nestin+, PSA-NCAM+, NeuN+ cells) and transcription factors (SOX2, Tbr1/2, Prox1) were significantly reduced under hyperoxia compared to control. Furthermore, regulators of neuronal plasticity (Nrp1, Nrg1, Syp, and Sema3a/f) were also drastically decreased. A single administration of dexmedetomidine prior to oxygen exposure resulted in a significant up-regulation of expression-profiles compared to hyperoxia. Our results suggest that dexmedetomidine may have neuroprotective effects in an acute hyperoxic model of the neonatal rat. PMID:28158247

  3. 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

  4. 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

  5. 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,

  6. Exposure to 1-bromopropane causes degeneration of noradrenergic axons in the rat brain.

    Science.gov (United States)

    Mohideen, Sahabudeen Sheik; Ichihara, Gaku; Ichihara, Sahoko; Nakamura, Shoji

    2011-07-11

    1-Bromopropane (1-BP) has been used as an alternative to ozone-depleting solvents. Previous studies showed that 1-BP is neurotoxic in animals and humans. In humans, exposure to 1-BP caused various neurological and neurobehavioral symptoms or signs including depressive or irritated mood. However, the neurobiological changes underlying the depressive symptoms induced by 1-BP remain to be determined. The depressive symptoms are thought to be associated with degeneration of axons containing noradrenaline and serotonin. Based on this hypothesis, the present study examined the effects of repeated exposure to 1-BP on serotonergic and noradrenergic axons. Exposure to 1-BP induced dose-dependent decreases in the density of noradrenergic axons in the rat prefrontal cortex, but no apparent change in the density of serotonergic axons. The results suggest that depressive symptoms in workers exposed to 1-BP are due, at least in part, to the degeneration of noradrenergic axons in the brain.

  7. [Protective Effect of Schisandra Extract on Embryotoxicity and Reproductive Toxicity in Early Pregnant Rats Exposed to Benzo [a] pyrene].

    Science.gov (United States)

    Liang, Jing; Hou, Hai-yan; Sun, Yang; Chen, Ya-qiong

    2016-02-01

    To observe protective effects of Schisandra extract (SE) on embryotoxicity and reproductive toxicity of early pregnant rats exposed to Benzo[a]pyrene (Bap). Pregnant rat model was prepared using periodic screening cage method. Totally 50 female pregnant SD rats were divided into five groups by randomized block design according to the weight, i.e., the BaP model group, the low dose SE group, the middle dose SE group, the high dose SE group, the normal control group, 10 rats in each group. Rats in the BaP model group were administered with BaP at a daily dose of 2 mg/kg by gastrogavage. Rats in low, middle, and high dose SE groups were administered by gastrogavage with BaP (at a daily dose of 2 mg/kg) plus SE at a daily dose of 40, 200, and 1 000 mg/kg, respectively. Equal volume of olive oil was administered to rats in the normal control group by gastrogavage. All medication was performed for 8 successive days. Changes of rat body weight in each period were observed. The uterus embryonic total quality and ovary quality were measured, and organ index calculated. The number of corpus luteum, the number of embryo implantation, and the number of absorbed embryo were statistically calculated respectively. The implantation rate and the absorbed embryos rate were calculated. Serum levels of human chorionic gonadotrophin β (β-HCG) and progesterone (PROG) were detected by ELISA. Compared with the normal control group, the weight of 9-day pregnant rats, the number of embryo implantation, the uterus embryonic total index, ovary index, serum levels of β-HCG and PROG all decreased in the Bap model group with significant difference (P body weight, the uterus embryonic total index, and the PROG level increased in 3 dose SE groups (P pregnant rats exposed to Benzo[a]pyrene.

  8. Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain

    Directory of Open Access Journals (Sweden)

    Karimzadeh Fariba

    2012-06-01

    Full Text Available Abstract Background Essential oil of Pimpinella anisum L. Apiaceae (anise oil has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil. Methods The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP in in vivo and in vitro experimental models of rat brain. Results Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices. Conclusions Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested.

  9. Pulmonary Toxicity of a Formulated Preparation of Fenvalerate in Rats Subchronically Exposed by Nose Only Inhalation for 90 Days

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective The pulmonary toxicity of a commercially available formulated preparation of Fenvalerate (Fen), a synthetic pyrethroid has been studied in rats following subchronic nose only inhalation exposure route. Method  Adult male rats were exposed to Fen for 4h/day, 5 days a week for 90 days by using Flow Past Dynamic Nose only Inhalation Chamber. Results Fen exposed rats showed a significant increase in enzymatic activities of lactate dehydrogenase (LDH), acid phosphatase (ACP), alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT) which are considered as biochemical indicators of pulmonary damage. The concomitant histopathological examination of Fen exposed rats' lung revealed inflammatory changes viz., influx of mononuclear cells admixed with a few giant cells in alveolar lumen, hypetrophied bronchiolar and alveolar epithelial lining cells and presence of edematous fluid in alveolar lumen alongwith congested parenchymatous blood vessels. Conclusion These results for the first time indicate the pulmonary toxic effects of a commonly used formulated Fen preparation by using rat model and nose only inhalation as the route of exposure.

  10. 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.

  11. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines.

    Science.gov (United States)

    Choi, Sujean; Disilvio, Briana; Fernstrom, Madelyn H; Fernstrom, John D

    2013-11-01

    Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.

  12. NO-tryptophan: a new small molecule located in the rat brain

    Directory of Open Access Journals (Sweden)

    A. Mangas

    2016-09-01

    Full Text Available A highly specific monoclonal antibody directed against nitric oxide-tryptophan (NO-W with good affinity (10-9 M and specificity was developed. In the rat brain, using an indirect immunoperoxidase technique, cell bodies containing NO-W were exclusively found in the intermediate and dorsal parts of the lateral septal nucleus. No immunoreactive fibres were found in the rat brain. This work reports the first visualization and the morphological characteristics of cell bodies containing NO-W in the mammalian brain. The restricted distribution of NO-W in the rat brain suggests that this molecule could be involved in specific physiological mechanisms. 

  13. NO-tryptophan: a new small molecule located in the rat brain.

    Science.gov (United States)

    Mangas, A; Yajeya, J; González, N; Duleu, S; Geffard, M; Coveñas, R

    2016-09-22

    A highly specific monoclonal antibody directed against nitric oxide-tryptophan (NO-W) with good affinity (10-9 M) and specificity was developed. In the rat brain, using an indirect immunoperoxidase technique, cell bodies containing NO-W were exclusively found in the intermediate and dorsal parts of the lateral septal nucleus. No immunoreactive fibres were found in the rat brain. This work reports the first visualization and the morphological characteristics of cell bodies containing NO-W in the mammalian brain. The restricted distribution of NO-W in the rat brain suggests that this molecule could be involved in specific physiological mechanisms.

  14. Cigarette smoking induces heat shock protein 70 kDa expression and apoptosis in rat brain: Modulation by bacoside A.

    Science.gov (United States)

    Anbarasi, K; Kathirvel, G; Vani, G; Jayaraman, G; Shyamala Devi, C S

    2006-01-01

    Cigarette smoking is associated with the development of several diseases and antioxidants play a major role in the prevention of smoking-related diseases. Apoptosis is suggested as a possible contributing factor in the pathogenesis of smoking-induced toxicity. Therefore the present study was designed to investigate the influence of chronic cigarette smoke exposure on apoptosis and the modulatory effect of bacoside A (triterpenoid saponin isolated from the plant Bacopa monniera) on smoking-induced apoptosis in rat brain. Adult male albino rats of Wistar strain were exposed to cigarette smoke and simultaneously administered with bacoside A (10 mg/kg b.w./day, orally) for a period of 12 weeks. Expression of brain hsp70 was analyzed by Western blotting. Apoptosis was identified by DNA fragmentation, terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick end labeling (TUNEL) staining and transmission electron microscopy. The results showed that exposure to cigarette smoke induced hsp70 expression and apoptosis as characterized by DNA laddering, increased TUNEL-positive cells and ultrastructural apoptotic features in the brain. Administration of bacoside A prevented expression of hsp70 and neuronal apoptosis during cigarette smoking. We speculate that apoptosis may be responsible for the smoking-induced brain damage and bacoside A can protect the brain from the toxic effects of cigarette smoking.

  15. Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

    Science.gov (United States)

    Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

    2007-02-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time

  16. Anticancer and antioxidant properties of terpinolene in rat brain cells.

    Science.gov (United States)

    Aydin, Elanur; Türkez, Hasan; Taşdemir, Sener

    2013-09-01

    Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species. Although various biological activities of TPO have been demonstrated, its neurotoxicity has never been explored. In this in vitro study we investigated TPO's antiproliferative and/or cytotoxic properties using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test, genotoxic damage potential using the single-cell gel electrophoresis (SCGE), and oxidative effects through total antioxidant capacity (TAC) and total oxidative stress (TOS) in cultured primary rat neurons and N2a neuroblastoma cells. Dose-dependent effects of TPO (at 10 mg L(-1), 25 mg L(-1), 50 mg L(-1), 100 mg L(-1), 200 mg L(-1), and 400 mg L(-1)) were tested in both cell types. Significant (P<0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the dose of 100 mg L(-1) and in N2a neuroblastoma cells starting with 50 mg L(-1). TPO was not genotoxic in either cell type. In addition, TPO treatment at 10 mg L(-1), 25 mg L(-1), and 50 mg L(-1) increased TAC in primary rat neurons, but not in N2a cells. However, at concentrations above 50 mg L(-1) it increased TOS in both cell types. Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.

  17. DNA damage in nasal and brain tissues of canines exposed to air pollutants is associated with evidence of chronic brain inflammation and neurodegeneration.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Maronpot, Robert R; Torres-Jardon, Ricardo; Henríquez-Roldán, Carlos; Schoonhoven, Robert; Acuña-Ayala, Hilda; Villarreal-Calderón, Anna; Nakamura, Jun; Fernando, Reshan; Reed, William; Azzarelli, Biagio; Swenberg, James A

    2003-01-01

    Acute, subchronic, or chronic exposures to particulate matter (PM) and pollutant gases affect people in urban areas and those exposed to fires, disasters, and wars. Respiratory tract inflammation, production of mediators of inflammation capable of reaching the brain, systemic circulation of PM, and disruption of the nasal respiratory and olfactory barriers are likely in these populations. DNA damage is crucial in aging and in age-associated diseases such as Alzheimer's disease. We evaluated apurinic/apyrimidinic (AP) sites in nasal and brain genomic DNA, and explored by immunohistochemistry the expression of nuclear factor NFkappaB p65, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX2), metallothionein I and II, apolipoprotein E, amyloid precursor protein (APP), and beta-amyloid(1-42) in healthy dogs naturally exposed to urban pollution in Mexico City. Nickel (Ni) and vanadium (V) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Forty mongrel dogs, ages 7 days-10 years were studied (14 controls from Tlaxcala and 26 exposed to urban pollution in South West Metropolitan Mexico City (SWMMC)). Nasal respiratory and olfactory epithelium were found to be early pollutant targets. Olfactory bulb and hippocampal AP sites were significantly higher in exposed than in control age matched animals. Ni and V were present in a gradient from olfactory mucosa > olfactory bulb > frontal cortex. Exposed dogs had (a) nuclear neuronal NFkappaB p65, (b) endothelial, glial and neuronal iNOS, (c) endothelial and glial COX2, (d) ApoE in neuronal, glial and vascular cells, and (e) APP and beta amyloid(1-42) in neurons, diffuse plaques (the earliest at age 11 months), and in subarachnoid blood vessels. Increased AP sites and the inflammatory and stress protein brain responses were early and significant in dogs exposed to urban pollution. Oil combustion PM-associated metals Ni and V were detected in the brain. There was an acceleration of Alzheimer

  18. Gene Expression Profiling during Pregnancy in Rat Brain Tissue

    Directory of Open Access Journals (Sweden)

    Phyllis E. Mann

    2014-03-01

    Full Text Available The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases “expectant brain” and “maternal brain”. Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1 whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

  19. Chronic noise stress-induced alterations of glutamate and gamma-aminobutyric acid and their metabolism in the rat brain

    Directory of Open Access Journals (Sweden)

    Amajad Iqbal Kazi

    2014-01-01

    Full Text Available Chronic stress induces neurochemical changes that include neurotransmitter imbalance in the brain. Noise is an environmental factor inducing stress. Chronic noise stress affects monoamine neurotransmitter systems in the central nervous system. The effect on other excitatory and inhibitory neurotransmitter systems is not known. The aim was to study the role of chronic noise stress on the glutamatergic and gamma-aminobutyric acid (GABAergic systems of the brain. Female Wistar rats (155 ± 5 g were unintentionally exposed to noise due to construction (75-95 db, 3-4 hours/day, 5 days a week for 7-8 weeks in the vicinity of the animal care facility. Glutamate/GABA levels and their metabolic enzymes were evaluated in different rat brain regions (cortex, hippocampus, striatum, and cerebellum and compared with age and gender matched nonexposed rats. Chronic noise stress decreased glutamate levels and glutaminase activity 27% and 33% in the cortex, 15% and 24% in the cerebellum. Glutamate levels increased 10% in the hippocampus, 28% in striatum and glutaminase activity 15% in striatum. Glutamine synthetase activity increased significantly in all brain regions studied, that is, cortex, hippocampus, striatum, and cerebellum (P < 0.05. Noise stress-increased GABA levels and glutamate alpha decarboxylase activity 20% and 45% in the cortex, 13% and 28% in the hippocampus respectively. GABA levels and glutamate alpha decarboxylase activity decreased 15% and 14%, respectively in the striatum. GABA transaminase activity was significantly reduced in the cortex (55%, hippocampus (17%, and cerebellum (33%. Chronic noise stress differentially affected glutamatergic and GABAergic neurotransmitter systems in the rat brain, which may alter glutamate and GABA neurotransmission.

  20. Toxicological assessments of rats exposed prenatally to inhaled vapors of gasoline and gasoline-ethanol blends.

    Science.gov (United States)

    Bushnell, Philip J; Beasley, Tracey E; Evansky, Paul A; Martin, Sheppard A; McDaniel, Katherine L; Moser, Virginia C; Luebke, Robert W; Norwood, Joel; Copeland, Carey B; Kleindienst, Tadeusz E; Lonneman, William A; Rogers, John M

    2015-01-01

    The primary alternative to petroleum-based fuels is ethanol, which may be blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol and the lack of information about the neurodevelopmental toxicity of ethanol-blended fuels prompted the present work. Pregnant Long-Evans rats were exposed for 6.5h/day on days 9-20 of gestation to clean air or vapors of gasoline containing no ethanol (E0) or gasoline blended with 15% ethanol (E15) or 85% ethanol (E85) at nominal concentrations of 3000, 6000, or 9000 ppm. Estimated maternal peak blood ethanol concentrations were less than 5mg/dL for all exposures. No overt toxicity in the dams was observed, although pregnant dams exposed to 9000 ppm of E0 or E85 gained more weight per gram of food consumed during the 12 days of exposure than did controls. Fuel vapors did not affect litter size or weight, or postnatal weight gain in the offspring. Tests of motor activity and a functional observational battery (FOB) administered to the offspring between post-natal day (PND) 27-29 and PND 56-63 revealed an increase in vertical activity counts in the 3000- and 9000-ppm groups in the E85 experiment on PND 63 and a few small changes in sensorimotor responses in the FOB that were not monotonically related to exposure concentration in any experiment. Neither cell-mediated nor humoral immunity were affected in a concentration-related manner by exposure to any of the vapors in 6-week-old male or female offspring. Systematic concentration-related differences in systolic blood pressure were not observed in rats tested at 3 and 6 months of age in any experiment. No systematic differences were observed in serum glucose or glycated hemoglobin A1c (a marker of long-term glucose

  1. Inhibition of lipid peroxidation in rat brain by nifedipine and clorazepate after electrically induced seizures.

    Science.gov (United States)

    Kułak, W; Sobaniec, W; Sobaniec-Lotowska, M

    1993-01-01

    The effect of nifedipine and clorazepate on the concentration of lipid peroxides (LP) in rat brain, and the characteristics of electrically induced seizures were assessed. A significant increase in the concentration of brain LP after electroshock was found. Both nifedipine (1.00 mg/kg per os) and clorazepate (20 mg/kg intraperitoneally) decreased the levels of LP in the rat brain after electroshock. Nifedipine combined with clorazepate brought an inhibition of LP formation and an additive anticonvulsant activity.

  2. 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.

  3. Remote ischemic preconditioning provides neuroprotection: impact on ketamine-induced neuroapoptosis in the developing rat brain.

    Science.gov (United States)

    Ma, W; Cao, Y-Y; Qu, S; Ma, S-S; Wang, J-Z; Deng, L-Q; Yuan, W-J; Meng, J-H

    2016-12-01

    Previous studies have demonstrated that the commonly used anesthetic ketamine can acutely increase apoptosis and have long-lasting detrimental effects on cognitive function as the animal matures. Remote ischemic preconditioning (RIPC) has been confirmed to have a cerebral protective role in animal models of brain damage. The aim of this study was to investigate whether RIPC can protect the developing brain from anesthetic-induced neurotoxicity. To investigate the protective properties of RIPC, 60 new-born Sprague-Dawley (SD) rats were randomly allocated into four groups: ketamine (20 mg/kg was diluted in saline, six times at an interval of 2 hours); RIPC (left hind row ischemia 5 min, reperfusion 5 min, a total of four cycles); ketamine + RIPC: RIPC was induced at postnatal day 5 and rats underwent the same treatment with the ketamine group after 48 hours; and saline (group vehicle). Neuronal apoptosis in the frontal cortex and hippocampal CA1 region was measured 24 h after treatment using immunohistochemistry of cleaved caspase-3. Learning and memory abilities were tested at the age of 60 days by Morris water maze test. The percentage of cleaved caspase-3 immunohistochemical staining positive cells in the ketamine + RIPC group showed a more marked decline in neuronal apoptosis of the CA1 region than that in the ketamine group (p 0.05). The mice exposed to RIPC alone showed no difference from the saline-treated mice. Moreover, RIPC significantly reversed the learning and memory deficits observed at 60 days of age. Our data indicate that RIPC treatment provides protection against ketamine-induced neuroapoptosis in the frontal cerebral cortex but not in the hippocampal CA1 region in developing rats and attenuates long-term behavioural deficits as the animals mature, suggesting a new possible strategy for neuroprotection.

  4. Weakness in the mechanical properties of the femurs of growing female rats exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Brzoska, Malgorzata M.; Moniuszko-Jakoniuk, Janina [Medical University of Bialystok, Department of Toxicology, Bialystok (Poland); Majewska, Katarzyna [University of Warmia and Mazury (Poland). Faculty of Food Science

    2005-09-01

    The study assessed the effect of cadmium (Cd) intoxication on the risk of deformities and fractures of the growing bones of female rats, in order to model human exposure to this metal. For this purpose, bone mineral density and mechanical properties of the proximal and distal ends and diaphysis of the femur were investigated in female Wistar rats exposed to 1, 5 and 50 mg Cd/l in drinking water for 3, 6, 9 and 12 months after the onset of weaning. Daily Cd doses received from drinking water during the treatment period were in the following ranges: 0.059-0.219, 0.236-1.005 and 2.247-9.649 mg/kg body weight at 1, 5 and 50 mg Cd/l, respectively. Biomechanical properties of the femoral proximal and distal ends were evaluated in a compression test, and those of the femoral diaphysis in a cutting test, with loading perpendicular to the longitudinal axis of the bone in all tests. The mineralization and mechanical properties of the bone tissue at various locations on the femur were affected by exposure to Cd in a dose- and duration-dependent manner. Exposure to 1 mg Cd/l (corresponding to low human exposure) during skeletal development weakened the fracture strength of the femoral neck and the trabecular bone at the level of the distal end of the femur and affected the elastic properties of the cortical bone at the femoral diaphysis. At higher levels of Cd exposure, adverse effects were generally observed after a shorter exposure period than for 1 mg Cd/l, and were more advanced. The cadmium-induced weakening of the biomechanical properties of bone at particular sites on the femur correlated with the decreased bone mineralization. The results indicate that even a low exposure to Cd may affect the mineralization and biomechanical properties of growing bone, thus enhancing the risk of fracture. (orig.)

  5. Weakness in the mechanical properties of the femur of growing female rats exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Brzoska, Malgorzata M.; Moniuszko-Jakoniuk, Janina [Medical University of Bialystok, Department of Toxicology, Bialystok (Poland); Majewska, Katarzyna [University of Warmia and Mazury, Olsztyn (Poland). Faculty of Food Science

    2005-05-01

    This study was aimed at assessing the effect of cadmium (Cd) intoxication on the risk of deformities and fractures of the growing bone on a female rat model of human exposure to this metal. For this purpose, bone mineral density (BMD) and mechanical properties of the proximal and distal ends and diaphysis of the femur were investigated in female Wistar rats exposed to 1, 5, and 50 mg Cd L{sup -1} in drinking water for 3, 6, 9, and 12 months since weaning. Daily Cd doses received from the drinking water during the treatment period were in the ranges 0.059-0.219, 0.236-1.005, and 2.247-9.649 mg kg{sup -1} body weight at 1, 5, and 50 mg Cd L{sup -1}, respectively. Biomechanical properties of the femoral proximal and distal ends were evaluated in a compression test and those of the femoral diaphysis in a cutting test with loading perpendicular to the bone longitudinal axis in all tests. Cd dose- and exposure duration-dependently affected the mineralization and mechanical properties of the bone tissue at various locations of the femur. Exposure to 1 mg Cd L{sup -1} (corresponding to low human exposure) during skeletal development weakened the fracture strength of the femoral neck and of the trabecular bone at the level of the distal end of the femur and affected the elastic properties of the cortical bone at the femoral diaphysis. At the higher levels of Cd treatment, the adverse action generally occurred after shorter exposure than at 1 mg Cd L{sup -1} and was more seriously advanced. The Cd-induced weakening in the bone biomechanical properties at particular sites of the femur correlated with the decreased bone mineralization. The results indicate that even low exposure to Cd may affect the mineralization and biomechanical properties of growing bone, thus increasing the risk of fractures. (orig.)

  6. Formation of Hydroxymethyl DNA Adducts in Rats Orally Exposed to Stable Isotope Labeled Methanol

    Science.gov (United States)

    Lu, Kun; Gul, Husamettin; Upton, Patricia B.; Moeller, Benjamin C.; Swenberg, James A.

    2012-01-01

    Methanol is a large volume industrial chemical and widely used solvent and fuel additive. Methanol’s well known toxicity and use in a wide spectrum of applications has raised long-standing environmental issues over its safety, including its carcinogenicity. Methanol has not been listed as a carcinogen by any regulatory agency; however, there are debates about its carcinogenic potential. Formaldehyde, a metabolite of methanol, has been proposed to be responsible for the carcinogenesis of methanol. Formaldehyde is a known carcinogen and actively targets DNA and protein, causing diverse DNA and protein damage. However, formaldehyde-induced DNA adducts arising from the metabolism of methanol have not been reported previously, largely due to the absence of suitable DNA biomarkers and the inability to differentiate what was due to methanol compared with the substantial background of endogenous formaldehyde. Recently, we developed a unique approach combining highly sensitive liquid chromatography-mass spectrometry methods and exposure to stable isotope labeled chemicals to simultaneously quantify formaldehyde-specific endogenous and exogenous DNA adducts. In this study, rats were exposed daily to 500 or 2000 mg/kg [13CD4]-methanol by gavage for 5 days. Our data demonstrate that labeled formaldehyde arising from [13CD4]-methanol induced hydroxymethyl DNA adducts in multiple tissues in a dose-dependent manner. The results also demonstrated that the number of exogenous DNA adducts was lower than the number of endogenous hydroxymethyl DNA adducts in all tissues of rats administered 500 mg/kg per day for 5 days, a lethal dose to humans, even after incorporating an average factor of 4 for reduced metabolism due to isotope effects of deuterium-labeled methanol into account. PMID:22157354

  7. Mild traumatic brain injury with social defeat stress alters anxiety, contextual fear extinction, and limbic monoamines in adult rats

    Directory of Open Access Journals (Sweden)

    Daniel eDavies

    2016-04-01

    Full Text Available Mild traumatic brain injury (mTBI produces symptoms similar to those typifying posttraumatic stress disorder (PTSD in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM, or for contextual fear conditioning and extinction. Brains were collected 24 hr after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes.

  8. Memory, learning, and participation of the cholinergic system in young rats exposed to environmental enrichment.

    Science.gov (United States)

    Lima, Aline P A S; Silva, Kelly; Padovan, Cláudia Maria; Almeida, Sebastião Sousa; Fukuda, Marisa Tomoe Hebihara

    2014-02-01

    The present study demonstrates the consequences of animal exposure to an enriched environment compared to animals living in a standard environment regarding learning and space memory. Male albino Wistar rats were exposed to an enriched environment for 4 weeks after the lactation period and tested in the Morris water maze in the distal and proximal clue version and in the arena. In the former test, the animals were tested at 50 days of age with 12 daily trials on two consecutive days. At the end of each session, scopolamine at the dose of 0.6 mg/kg/ml or saline solution was injected intraperitoneally. Twenty-eight days after the first phase, a new test consisting of a single trial was held (retest). An independent group of animals receiving no drug was subjected to the arena test and to the proximal clue version of the Morris maze. In the distal clue version the results did not show differences between groups in the first phase of the experiment. After 28 days (retest), the animals reared in a standard environment and treated with scopolamine exhibited a significant increase in latency compared to the group receiving the same drug and stimulated and to the group receiving saline. The arena data demonstrated a significant increase in exploratory activity in the group of animals reared in an enriched environment. The proximal clue version of the Morris maze did not show differences between groups. The results of the present study indicate that animals exposed to environmental enrichment react less to the amnesic effects of scopolamine and show an increase in exploratory activity.

  9. Selective glial vulnerability following transient global ischemia in rat brain.

    Science.gov (United States)

    Petito, C K; Olarte, J P; Roberts, B; Nowak, T S; Pulsinelli, W A

    1998-03-01

    Global cerebral ischemia selectively damages neurons, but its contribution to glial cell death is uncertain. Accordingly, adult male rats were sacrificed by perfusion fixation at 1, 2, 3, 5, and 14 days following 10 minutes of global ischemia. This insult produces CA1 hippocampal neuronal death at post-ischemic (PI) day 3, but minor or no damage to neurons in other regions. In situ end labeling (ISEL) and immunohistochemistry identified fragmented DNA of dead or dying glia and distinguished glial subtypes. Rare ISEL-positive oligodendroglia, astrocytes, and microglia were present in control brain. Apoptotic bodies and ISEL-positive glia significantly increased at PI day 1 in cortex and thalamus (p < 0.05), but were similar to controls in other regions and at other PI intervals. Most were oligodendroglia, although ISEL-positive microglia and astrocytes were also observed. These results show that oligodendroglia die rapidly after brief global ischemia and are more sensitive than neurons in certain brain regions. Their selective vulnerability to ischemia may be responsible for the delayed white matter damage following anoxia or CO poisoning or that associated with white matter arteriopathies. Glial apoptosis could contribute to the DNA ladders of apoptotic oligonucleosomes that have been found in post-ischemic brain.

  10. Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Periyasamy, S.; Hoss, W. (Univ. of Toledo, OH (USA))

    1990-01-01

    The effects of various subtype-selective opioid agonists and antagonists on the phosphoinositide (PI) turnover response were investigated in the rat brain. The {kappa}-agonists U-50,488H and ketocyclazocine produced a concentration-dependent increase in the accumulation of IP's in hippocampal slices. The other {kappa}-agonists Dynorphin-A (1-13) amide, and its protected analog D(Ala){sup 2}-dynorphin-A (1-13) amide also produced a significant increase in the formation of ({sup 3}H)-IP's, whereas the {mu}-selective agonists (D-Ala{sup 2}-N-Me-Phe{sup 4}-Gly{sup 5}-ol)-enkephalin and morphine and the {delta}-selective agonist (D-Pen{sup 2,5})-enkephalin were ineffective. The increase in IP's formation elicited by U-50,488H was partially antagonized by naloxone and more completely antagonized by the {kappa}-selective antagonists nor-binaltorphimine and MR 2266. The formation of IP's induced by U-50,488H varies with the regions of the brain used, being highest in hippocampus and amygdala, and lowest in striatum and pons-medullar. The results indicate that brain {kappa}- but neither {mu}- nor {delta}- receptors are coupled to the PI turnover response.

  11. Quinolinic acid induces oxidative stress in rat brain synaptosomes.

    Science.gov (United States)

    Santamaría, A; Galván-Arzate, S; Lisý, V; Ali, S F; Duhart, H M; Osorio-Rico, L; Ríos, C; St'astný, F

    2001-03-26

    The oxidative action of quinolinic acid (QUIN), and the protective effects of glutathione (GSH), and 2-amino-5-phosphonovaleric acid (APV), were tested in rat brain synaptosomes, Reactive oxygen species (ROS) formation was quantified after the exposure of synaptosomes to increasing concentrations of QUIN (25-500 microM). The potency of QUIN to induce lipid peroxidation (LP) was tested as a regional index of thiobarbituric acid-reactive substances (TBARS) production, and the antioxidant actions of both GSH (50 microM) and APV (250 microM) on QUIN-induced LP were evaluated in synaptosomes prepared from different brain regions. QUIN induced concentration-dependent increases in ROS formation and TBARS in all regions analyzed, but increased production of fluorescent peroxidized lipids only in the striatum and the hippocampus, whereas both GSH and APV decreased this index. These results suggest that the excitotoxic action of QUIN involves regional selectivity in the oxidative status of brain synaptosomes, and may be prevented by substances exhibiting antagonism at the NMDA receptor.

  12. Reduced number of alpha- and beta-adrenergic receptors in the myocardium of rats exposed to tobacco smoke

    Energy Technology Data Exchange (ETDEWEB)

    Larue, D.; Kato, G.

    1981-04-09

    The concentration of alpha- and beta-adrenergic receptors--as measured by specific (/sup 3/H)WB-4101 and (-)-(/sup 3/H)dihydroalprenolol binding--was diminished by 60% below control values in the hearts of rats exposed to tobacco smoke. These changes in receptor numbers took place almost immediately after tobacco smoke exposure and were rapidly reversible after termination of the exposure. The dissociation constant, KD, for (/sup 3/H)WB-4101 was identical in exposed (KD . 0.34 +/- 0.09 nM) and control (KD . 0.35 +/- 0.07 nM) hearts but was significantly different in the case of (-)-(3H)dihydroalprenolol binding (exposed, KD . 2.83 +/- 0.30 mM vs. control KD . 5.22 +/- 0.61 nM). For beta-receptor binding there was no significant difference between exposed and control animals in the Ki values for (-)-epinephrine, (-)-norepinephrine, (-)-alprenolol, (+/-)-propranolol or timolol. (-)-Isoproterenol, however, was found to bind with lower affinity in exposed compared with control hearts. For alpha-receptor binding there was no significant difference between control and 'smoked' animals in the Ki values for (-)-epinephrine, (-0)-norepinephrine or phentolamine. The decrease in alpha- and beta-adrenergic receptor concentration may be related to the phenomenon of receptor desensitization resulting from a release of catecholamines in rats exposed to tobacco smoke.

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

    Science.gov (United States)

    Ho, Yuen-Shan; Yang, Xifei; Yeung, Sze-Chun; Chiu, Kin; Lau, Chi-Fai; Tsang, Andrea Wing-Ting; Mak, Judith Choi-Wo; Chang, Raymond Chuen-Chung

    2012-01-01

    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.

  14. Early and later life stress alter brain activity and sleep in rats.

    Directory of Open Access Journals (Sweden)

    Jelena Mrdalj

    Full Text Available Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2-14 male rats were exposed to either long maternal separation (180 min or brief maternal separation (10 min. Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Early and later life stress alter brain activity and sleep in rats.

    Science.gov (United States)

    Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

    2013-01-01

    Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2-14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.

  17. Antibodies to the α1-adrenergic receptor cause vascular impairments in rat brain as demonstrated by magnetic resonance angiography.

    Directory of Open Access Journals (Sweden)

    Peter Karczewski

    Full Text Available BACKGROUND: Circulating agonistic autoantibodies acting at G protein-coupled receptors have been associated with numerous sever pathologies in humans. Antibodies directed predominantly against the α(1-adrenergig receptor were detected in patients suffering from widespread diseases such as hypertension and type 2 diabetes. Their deleterious action has been demonstrated for peripheral organs. We postulate that antibodies to the α(1-adrenergig receptor are relevant pathomolecules in diseases of the central nervous system associated with vascular impairments. METHODOLOGY/PRINCIPAL FINDINGS: Using a rat model we studied the long-term action of antibodies against the α(1-adrenergig receptor either induced by immunization with a receptor peptide or applied by intravenous injection. The vasculature in the rat brains was investigated by time-of-flight magnetic resonance angiography using a 9.4 Tesla small animal MR imaging system. Visual examination of maximum-intensity-projections (MIPs of brain angiographs revealed the development of vascular defects in antibody- exposed animals between three and eight months of treatment. Relative vascular areas were derived from representative MIP image sections by grayscale analysis and used to form an index of vascular circulation. Animals exposed to the action of α(1-adrenergig receptor antibodies showed significantly reduced vascular areas (p<0.05. Calculated index values indicated attenuated blood flow in both antibody-treated cohorts compared to their respective controls reaching with (relative units ± standard error, n = 10 0.839 ± 0.026 versus 0.919 ± 0.026 statistical significance (p<0.05 for peptide-immunized rats. CONCLUSION/SIGNIFICANCE: We present evidence that antibodies to the α(1-adrenergig receptor cause cerebrovascular impairments in the rat. Our findings suggest the pathological significance of these antibodies in pathologies of the human central nervous system linked to impairments of

  18. Gallic acid improved behavior, brain electrophysiology, and inflammation in a rat model of traumatic brain injury.

    Science.gov (United States)

    Sarkaki, Alireza; Farbood, Yaghoub; Gharib-Naseri, Mohammad Kazem; Badavi, Mohammad; Mansouri, Mohammad Taghi; Haghparast, Abbas; Mirshekar, Mohammad Ali

    2015-08-01

    Traumatic brain injury (TBI) is one of the main causes of intellectual and cognitive disabilities. In the clinic it is essential to limit the development of cognitive impairment after TBI. In this study, the effects of gallic acid (GA; 100 mg/kg, per oral, from 7 days before to 2 days after TBI induction) on neurological score, passive avoidance memory, long-term potentiation (LTP) deficits, and levels of proinflammatory cytokines including interleukin-1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in the brain have been evaluated. Brain injury was induced following Marmarou's method. Data were analyzed by one-way and repeated measures ANOVA followed by Tukey's post-hoc test. The results indicated that memory was significantly impaired (p memory and LTP in the TBI rats. The brain tissue levels of IL-1β, IL-6, and TNF-α were significantly reduced (p electrophysiological, and inflammatory disorders, probably via the decrease of cerebral proinflammatory cytokines.

  19. Endothelial dysfunction in normal and prediabetic rats with metabolic syndrome exposed by oral gavage to carbon black nanoparticles

    DEFF Research Database (Denmark)

    Folkmann, Janne Kjærsgaard; Vesterdal, Lise Kristine; Sheykhzade, Majid

    2012-01-01

    Exposure to nanosized particles may increase the risk of cardiovascular diseases by endothelial dysfunction, particularly in susceptible subjects with metabolic syndrome. We investigated vasomotor dysfunction in aorta from obese and lean Zucker rats after oral exposure to nanosized carbon black (CB....... In conclusion, repeated oral exposure to CB was associated with endothelial dysfunction in rats, further aggravating the effect of metabolic syndrome.......). Rats were exposed to 1 or 10 weekly doses of 0, 0.064, 0.64 or 6.4mg/kg bodyweight and sacrificed 24h or 13 weeks later. The exposure to 10 doses of 0.064 or 0.64mg/kg reduced the acetylcholine-induced vasorelaxation in the lean and obese rats. The half maximal effect concentration values increased...

  20. Dietary choline deprivation impairs rat brain mitochondrial function and behavioral phenotype.

    Science.gov (United States)

    Pacelli, Consiglia; Coluccia, Addolorata; Grattagliano, Ignazio; Cocco, Tiziana; Petrosillo, Giuseppe; Paradies, Giuseppe; De Nitto, Emanuele; Massaro, Antonio; Persichella, Michele; Borracci, Pietro; Portincasa, Piero; Carratù, Maria Rosaria

    2010-06-01

    Dietary choline deprivation (CD) is associated with behavioral changes, but mechanisms underlying these detrimental effects are not well characterized. For instance, no literature data are available concerning the CD effects on brain mitochondrial function related to impairment in cognition. Therefore, we investigated brain mitochondrial function and redox status in male Wistar rats fed a CD diet for 28 d. Moreover, the CD behavioral phenotype was characterized. Compared with rats fed a control diet (CTRL), CD rats showed lower NAD-dependent mitochondrial state III and state IV respiration, 40% lower complex I activity, and significantly higher reactive oxygen species production. Total glutathione was oxidatively consumed more in CD than in CTRL rats and the rate of protein oxidation was 40% higher in CD than in CTRL rats, reflecting an oxidative stress condition. The mitochondrial concentrations of cardiolipin, a phospholipid required for optimal activity of complex I, was 20% lower in CD rats than in CTRL rats. Compared with CTRL rats, the behavioral phenotype of CD rats was characterized by impairment in motor coordination and motor learning assessed with the rotarod/accelerod test. Furthermore, compared with CTRL rats, CD rats were less capable of learning the active avoidance task and the number of attempts they made to avoid foot shock was fewer. The results suggest that CD-induced dysfunction in brain mitochondria may be responsible for impairment in cognition and underline that, similar to the liver, the brain also needs an adequate choline supply for its normal functioning.

  1. Effects of Xylopia aethiopica (Annonaceae) fruit methanol extract on gamma-radiation-induced oxidative stress in brain of adult male Wistar rats.

    Science.gov (United States)

    Adaramoye, O A; Popoola, Bosede O; Farombi, E O

    2010-09-01

    Xylopia aethiopica (XA) (Annonaceae) possesses great nutritional and medicinal values. This study was designed to investigate the effects of XA fruit methanol extract on oxidative stress in brain of rats exposed to whole body gamma-radiation (5 Gy). Vitamin C (VC) served as standard antioxidant. Forty-four rats were divided into 4 groups of 11 rats each. One group served as control, two different groups were treated with XA and VC (250 mg/kg), 6 weeks before and 8 weeks after irradiation, and fourth group was only irradiated. Rats were sacrificed 1 and 8 weeks after irradiation. The antioxidant status, viz. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and glutathione (GSH) were estimated. Results indicate a significant increase (p < 0.05) in levels of brain LPO after irradiation. LPO increased by 90% and 151%, after 1 and 8 weeks of irradiation, respectively. Irradiation caused significant (p < 0.05) decreases in levels of GSH and GST by 61% and 43% after 1 week and, 75% and 73%, respectively, after 8 weeks of exposure. CAT and SOD levels were decreased by 62% and 68%, respectively, after 8 weeks of irradiation. Treatment with XA and VC ameliorated the radiation-induced decreases in antioxidant status of the animals. These suggest that XA could have beneficial effect by inhibiting oxidative damage in brain of exposed rats.

  2. Comparison of transfer and effects of Cd on rats exposed in a short experimental snail-rat food chain or to CdCl2 dosed food.

    Science.gov (United States)

    Hispard, F; de Vaufleury, A; Cosson, R P; Devaux, S; Scheifler, R; Coeurdassier, M; Gimbert, F; Martin, H; Richert, L; Berthelot, A; Badot, P-M

    2008-04-01

    Transfer and toxic effects of two cadmium (Cd) forms, inorganic (CdCl2 dosed rat food) or organic (contaminated snail-based rat food) were studied in Wistar rat. Cd concentrations in rat food were 0 and 2.5 microg Cd g(-1) for both inorganic and organic forms and a high concentration of 100 microg Cd g(-1) was also tested for the inorganic form. Rats were exposed for four weeks to contaminated food. Both forms of Cd were bioavailable to rats, with a percentage of transfer from food to rats of around 1% for all contaminated groups. Cd concentrations in rat tissues increased with increasing Cd concentrations in the food. Rats fed with organic form of Cd accumulated significantly more Cd in the main organ for Cd toxicity, the kidney, than those eating the inorganic form. Survival was not affected for any rat group but a decrease in growth and food consumption was observed for the inorganic form. As a defence system against Cd toxicity, rats increased their metallothionein (MT) synthesis at the highest Cd concentration in the target organs (kidney, liver and small intestine) and even did the same at low Cd concentrations (2.5 microg Cd g(-1)) in the kidney. At this low Cd concentration, MT induction was lower in the small intestine of rats ingesting organic Cd than those ingesting inorganic Cd. Bioavailability of organic and inorganic forms of Cd was similar, but subsequent Cd distribution within organs was different. This quantification of the trophic transfer of both inorganic and organic forms of a toxicant is a basis for a better assessment of the fate and effects of chemicals in food webs.

  3. Factors influencing aggression toward females by male rats exposed to anabolic androgenic steroids during puberty.

    Science.gov (United States)

    Cunningham, Rebecca L; McGinnis, Marilyn Y

    2007-01-01

    Previous results showed that male rats pubertally exposed to anabolic androgenic steroids (AAS) displayed aggression towards females in response to physical provocation. This experiment examined two factors that may modulate AAS-induced behavior towards females: olfactory cues and frustration. Gonadally intact males began one of three AAS treatments at puberty (D40): testosterone propionate (T), stanozolol (S), T+S, or vehicle control. To test for the relevance of olfactory cues in the elicitation of behavior toward females, a hidden neighbor paradigm was used. The proximal stimulus was an ovariectomized (OVX) female, estrogen plus progesterone (E+P) female, or an E+P female with tape-obstructed vagina (OBS). Distal olfactory cues from a hidden neighbor were delivered from a separate cage connected to the testing arena. The vaginally obstructed, sexually receptive female (OBS) was used to determine the effects of frustration on behavior by AAS males. Both sexual and aggressive behaviors were measured. The presence of distal olfactory cues had no effect on either sexual or aggressive behavior. In the presence of E+P and OBS females, all males displayed sex behaviors, not aggression. However, AAS males displayed significantly more aggression towards proximal OVX females than controls. AAS males mounted OBS females significantly more than controls, indicating a persistence of once rewarded behavior. These results suggest (1) proximal cues of the conspecific female are more salient than distal olfactory cues in determining behavior and (2) AAS males display frustration-induced persistence in response to vaginally obstructed receptive females.

  4. Lipopolysaccharide-induced expression of IP-10 mRNA in rat brain and in cultured rat astrocytes and microglia

    NARCIS (Netherlands)

    Ren, LQ; Gourmala, N; Boddeke, HWGM; Gebicke-Haerter, PJ

    1998-01-01

    Using mRNA differential display technique, we have found a differentially expressed band in rat brain, designated HAP(2)G1, which was the strongest one induced in response to peripheral administration of lipopolysaccharide (LPS). Sequence analysis showed that HAP(2)G1 cDNA is the rat homologue of th

  5. The Effect of Citrus aurantium on Uterus Apoptosis and Serum Antioxidants in Rats Exposed to Electromagnetic Fields

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    Mansouri Elham

    2014-10-01

    Full Text Available Objective: In the industrial world, almost everyone is unavoidably exposed to ambient electromagnetic field (EMF generated from various technical and household appliances. Thus, the aim of this study was to evaluate the diminishing effects of Citrus aurantium on uterus cell injury induced by EMF. Materials and Methods: In order to examine this, 40 female Wistar rats were selected and kept for 1 week in quarantine, and then, subdivided into two groups of 20 rats and were exposed to 40 Hz of EMF (non-ionizing radiation, 0.1 tesla for 6 weeks. Group 1 received 3 cc/rat Citrus aurantium juice, and group 2 only received 3 cc Citrus aurantium. The control group only received 3 cc water using gavage method. The materials were processed and apoptosis was observed under a light microscope using TUNEL method. Results: In the experimental rats, apoptotic cells showed significant increase in the EMF groups. However, in the exposed group that received Citrus aurantium, apoptotic cells and serum malondialdehyde (MDA were decreased and superoxide dismutase (SOD was increased (P < 0.05. Conclusion: This study showed that EMF could induce cell injury on uterus tissue, and 3 cc Citrus aurantium juice has antioxidative effects on uterus tissue by reduction of apoptosis.

  6. Effects of Chronic Administration of Melatonin on Spatial Learning Ability and Long-term Potentiation in Lead-exposed and Control Rats

    Institute of Scientific and Technical Information of China (English)

    XIU-JING CAO; MING WANG; WEI-HENG CHEN; DA-MIAO ZHU; JIA-QI SHE; DI-YUN RUAN

    2009-01-01

    Objective To explore the changes in spatial learning performance and long-term potentiation (LTP) which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin (MT) for two months. Methods Experiment was performed in adult male Wistar rats (12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment). The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin (3 mg/kg) or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric garage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus (DG) area of the hippocampus in vivo. Results Low dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead. Conclusion Melatonin is not suitable for normal and lead-exposed children.

  7. Methylmercury Causes Blood-Brain Barrier Damage in Rats via Upregulation of Vascular Endothelial Growth Factor Expression

    Science.gov (United States)

    Takahashi, Tetsuya; Fujimura, Masatake; Koyama, Misaki; Kanazawa, Masato; Usuki, Fusako; Nishizawa, Masatoyo; Shimohata, Takayoshi

    2017-01-01

    Clinical manifestations of methylmercury (MeHg) intoxication include cerebellar ataxia, concentric constriction of visual fields, and sensory and auditory disturbances. The symptoms depend on the site of MeHg damage, such as the cerebellum and occipital lobes. However, the underlying mechanism of MeHg-induced tissue vulnerability remains to be elucidated. In the present study, we used a rat model of subacute MeHg intoxication to investigate possible MeHg-induced blood-brain barrier (BBB) damage. The model was established by exposing the rats to 20-ppm MeHg for up to 4 weeks; the rats exhibited severe cerebellar pathological changes, although there were no significant differences in mercury content among the different brain regions. BBB damage in the cerebellum after MeHg exposure was confirmed based on extravasation of endogenous immunoglobulin G (IgG) and decreased expression of rat endothelial cell antigen-1. Furthermore, expression of vascular endothelial growth factor (VEGF), a potent angiogenic growth factor, increased markedly in the cerebellum and mildly in the occipital lobe following MeHg exposure. VEGF expression was detected mainly in astrocytes of the BBB. Intravenous administration of anti-VEGF neutralizing antibody mildly reduced the rate of hind-limb crossing signs observed in MeHg-exposed rats. In conclusion, we demonstrated for the first time that MeHg induces BBB damage via upregulation of VEGF expression at the BBB in vivo. Further studies are required in order to determine whether treatment targeted at VEGF can ameliorate MeHg-induced toxicity. PMID:28118383

  8. Sarin-induced brain damage in rats is attenuated by delayed administration of midazolam.

    Science.gov (United States)

    Chapman, Shira; Yaakov, Guy; Egoz, Inbal; Rabinovitz, Ishai; Raveh, Lily; Kadar, Tamar; Gilat, Eran; Grauer, Ettie

    2015-07-01

    Sarin poisoned rats display a hyper-cholinergic activity including hypersalivation, tremors, seizures and death. Here we studied the time and dose effects of midazolam treatment following nerve agent exposure. Rats were exposed to sarin (1.2 LD50, 108 μg/kg, im), and treated 1 min later with TMB4 and atropine (TA 7.5 and 5 mg/kg, im, respectively). Midazolam was injected either at 1 min (1 mg/kg, im), or 1 h later (1 or 5 mg/kg i.m.). Cortical seizures were monitored by electrocorticogram (ECoG). At 5 weeks, rats were assessed in a water maze task, and then their brains were extracted for biochemical analysis and histological evaluation. Results revealed a time and dose dependent effects of midazolam treatment. Rats treated with TA only displayed acute signs of sarin intoxication, 29% died within 24h and the ECoG showed seizures for several hours. Animals that received midazolam within 1 min survived with only minor clinical signs but with no biochemical, behavioral, or histological sequel. Animals that lived to receive midazolam at 1h (87%) survived and the effects of the delayed administration were dose dependent. Midazolam 5 mg/kg significantly counteracted the acute signs of intoxication and the impaired behavioral performance, attenuated some of the inflammatory response with no effect on morphological damage. Midazolam 1mg/kg showed only a slight tendency to modulate the cognitive function. In addition, the delayed administration of both midazolam doses significantly attenuated ECoG compared to TA treatment only. These results suggest that following prolonged seizure, high dose midazolam is beneficial in counteracting adverse effects of sarin poisoning.

  9. Exposure to 900 MHz electromagnetic fields activates the mkp-1/ERK pathway and causes blood-brain barrier damage and cognitive impairment in rats.

    Science.gov (United States)

    Tang, Jun; Zhang, Yuan; Yang, Liming; Chen, Qianwei; Tan, Liang; Zuo, Shilun; Feng, Hua; Chen, Zhi; Zhu, Gang

    2015-03-19

    With the rapid increase in the number of mobile phone users, the potential adverse effects of the electromagnetic field radiation emitted by a mobile phone has become a serious concern. This study demonstrated, for the first time, the blood-brain barrier and cognitive changes in rats exposed to 900 MHz electromagnetic field (EMF) and aims to elucidate the potential molecular pathway underlying these changes. A total of 108 male Sprague-Dawley rats were exposed to a 900 MHz, 1 mW/cm(2) EMF or sham (unexposed) for 14 or 28 days (3h per day). The specific energy absorption rate (SAR) varied between 0.016 (whole body) and 2 W/kg (locally in the head). In addition, the Morris water maze test was used to examine spatial memory performance determination. Morphological changes were investigated by examining ultrastructural changes in the hippocampus and cortex, and the Evans Blue assay was used to assess blood brain barrier (BBB) damage. Immunostaining was performed to identify heme oxygenase-1 (HO-1)-positive neurons and albumin extravasation detection. Western blot was used to determine HO-1 expression, phosphorylated ERK expression and the upstream mediator, mkp-1 expression. We found that the frequency of crossing platforms and the percentage of time spent in the target quadrant were lower in rats exposed to EMF for 28 days than in rats exposed to EMF for 14 days and unexposed rats. Moreover, 28 days of EMF exposure induced cellular edema and neuronal cell organelle degeneration in the rat. In addition, damaged BBB permeability, which resulted in albumin and HO-1 extravasation were observed in the hippocampus and cortex. Thus, for the first time, we found that EMF exposure for 28 days induced the expression of mkp-1, resulting in ERK dephosphorylation. Taken together, these results demonstrated that exposure to 900 MHz EMF radiation for 28 days can significantly impair spatial memory and damage BBB permeability in rat by activating the mkp-1/ERK pathway.

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

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    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)

  11. No increases in biomarkers of genetic damage or pathological changes in heart and brain tissues in male rats administered methylphenidate hydrochloride (Ritalin) for 28 days.

    Science.gov (United States)

    Witt, Kristine L; Malarkey, David E; Hobbs, Cheryl A; Davis, Jeffrey P; Kissling, Grace E; Caspary, William; Travlos, Gregory; Recio, Leslie

    2010-01-01

    Following a 2005 report of chromosomal damage in children with attention deficit/hyperactivity disorder (ADHD) who were treated with the commonly prescribed medication methylphenidate (MPH), numerous studies have been conducted to clarify the risk for MPH-induced genetic damage. Although most of these studies reported no changes in genetic damage endpoints associated with exposure to MPH, one recent study (Andreazza et al. [2007]: Prog Neuropsychopharmacol Biol Psychiatry 31:1282-1288) reported an increase in DNA damage detected by the Comet assay in blood and brain cells of Wistar rats treated by intraperitoneal injection with 1, 2, or 10 mg/kg MPH; no increases in micronucleated lymphocyte frequencies were observed in these rats. To clarify these findings, we treated adult male Wistar Han rats with 0, 2, 10, or 25 mg/kg MPH by gavage once daily for 28 consecutive days and measured micronucleated reticulocyte (MN-RET) frequencies in blood, and DNA damage in blood, brain, and liver cells 4 hr after final dosing. Flow cytometric evaluation of blood revealed no significant increases in MN-RET. Comet assay evaluations of blood leukocytes and cells of the liver, as well as of the striatum, hippocampus, and frontal cortex of the brain showed no increases in DNA damage in MPH-treated rats in any of the three treatment groups. Thus, the previously reported observations of DNA damage in blood and brain tissue of rats exposed to MPH for 28 days were not confirmed in this study. Additionally, no histopathological changes in brain or heart, or elevated serum biomarkers of cardiac injury were observed in these MPH-exposed rats.

  12. Altered feeding patterns in rats exposed to a palatable cafeteria diet: increased snacking and its implications for development of obesity.

    Directory of Open Access Journals (Sweden)

    Sarah I Martire

    Full Text Available BACKGROUND: Rats prefer energy-rich foods over chow and eat them to excess. The pattern of eating elicited by this diet is unknown. We used the behavioral satiety sequence to classify an eating bout as a meal or snack and compared the eating patterns of rats fed an energy rich cafeteria diet or chow. METHODS: Eight week old male Sprague Dawley rats were exposed to lab chow or an energy-rich cafeteria diet (plus chow for 16 weeks. After 5, 10 and 15 weeks, home-cage overnight feeding behavior was recorded. Eating followed by grooming then resting or sleeping was classified as a meal; whereas eating not followed by the full sequence was classified as a snack. Numbers of meals and snacks, their duration, and waiting times between feeding bouts were compared between the two conditions. RESULTS: Cafeteria-fed rats ate more protein, fat and carbohydrate, consistently ingesting double the energy of chow-fed rats, and were significantly heavier by week 4. Cafeteria-fed rats tended to take multiple snacks between meals and ate fewer meals than chow-fed rats. They also ate more snacks at 5 weeks, were less effective at compensating for snacking by reducing meals, and the number of snacks in the majority of the cafeteria-fed rats was positively related to terminal body weights. CONCLUSIONS: Exposure to a palatable diet had long-term effects on feeding patterns. Rats became overweight because they initially ate more frequently and ultimately ate more of foods with higher energy density. The early increased snacking in young cafeteria-fed rats may represent the establishment of eating habits that promote weight gain.

  13. Altered feeding patterns in rats exposed to a palatable cafeteria diet: increased snacking and its implications for development of obesity.

    Science.gov (United States)

    Martire, Sarah I; Holmes, Nathan; Westbrook, R Fred; Morris, Margaret J

    2013-01-01

    Rats prefer energy-rich foods over chow and eat them to excess. The pattern of eating elicited by this diet is unknown. We used the behavioral satiety sequence to classify an eating bout as a meal or snack and compared the eating patterns of rats fed an energy rich cafeteria diet or chow. Eight week old male Sprague Dawley rats were exposed to lab chow or an energy-rich cafeteria diet (plus chow) for 16 weeks. After 5, 10 and 15 weeks, home-cage overnight feeding behavior was recorded. Eating followed by grooming then resting or sleeping was classified as a meal; whereas eating not followed by the full sequence was classified as a snack. Numbers of meals and snacks, their duration, and waiting times between feeding bouts were compared between the two conditions. Cafeteria-fed rats ate more protein, fat and carbohydrate, consistently ingesting double the energy of chow-fed rats, and were significantly heavier by week 4. Cafeteria-fed rats tended to take multiple snacks between meals and ate fewer meals than chow-fed rats. They also ate more snacks at 5 weeks, were less effective at compensating for snacking by reducing meals, and the number of snacks in the majority of the cafeteria-fed rats was positively related to terminal body weights. Exposure to a palatable diet had long-term effects on feeding patterns. Rats became overweight because they initially ate more frequently and ultimately ate more of foods with higher energy density. The early increased snacking in young cafeteria-fed rats may represent the establishment of eating habits that promote weight gain.

  14. Palm vitamin E reduces catecholamines, xanthine oxidase activity and gastric lesions in rats exposed to water-immersion restraint stress

    Directory of Open Access Journals (Sweden)

    Mohd Fahami Nur Azlina

    2012-05-01

    Full Text Available Abstract Background This study examined the effects of Palm vitamin E (PVE and α-tocopherol (α-TF supplementations on adrenalin, noradrenalin, xanthine oxidase plus dehydrogenase (XO + XD activities and gastric lesions in rats exposed to water-immersion restraint stress (WIRS. Methods Sixty male Sprague–Dawley rats (200-250 g were randomly divided into three equal sized groups. The control group was given a normal diet, while the treated groups received the same diet with oral supplementation of PVE or α-TF at 60 mg/kg body weight. After the treatment period of 28 days, each group was further subdivided into two groups with 10 rats without exposing them to stress and the other 10 rats were subjected to WIRS for 3.5 hours. Blood samples were taken to measure the adrenalin and noradrenalin levels. The rats were then sacrificed following which the stomach was excised and opened along the greater curvature and examined for lesions and XO + XD activities. Results The rats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementations of PVE and α-TF were able to reduce gastric lesions significantly in comparison to the stressed control group. WIRS increased plasma adrenalin and noradrenalin significantly. PVE and α-TF treatments reduced these parameters significantly compared to the stressed control. Conclusions Supplementations with either PVE or α-TF reduce the formation of gastric lesions. Their protective effect was related to their abilities to inhibit stress induced elevation of adrenalin and noradrenalin levels as well as through reduction in xanthine oxidase and dehydrogenase activities.

  15. Effects of Rambutan Peel Extract to The Number of Erythrocytes and Haemoglobin in Rats Exposed to Cigarette Smoke

    Science.gov (United States)

    Lisdiana; Dewi, F. K.

    2017-04-01

    Cigarette smoke is one of the exogenous free radicals sources. When it is inhaled, its activity may damage the structure of erythrocyte membrane function. The impacts of free radicals can be reduced through the provision of antioxidants. Rambutan fruit peel contains the phenolic compound in the form of polyphenols that are antioxidants. The purpose of this study is to determine the effect of rambutan fruit peel extracts to the number of erythrocytes and haemoglobin in rats exposed to cigarette smoke. This design used Post Test Control Group Design. A sample of 25 rats was divided into five groups, each group consisting of 5 rats. The positive control group (K+) were given a standard food and drinking water. The negative control group (K) by three cigarettes, the treatment group (KP1, KP2, KP3) by three cigarettes and skin extract of rambutan each treatment group with a dose 15 mg/kg, 30 mg/kg and 45 mg/kg for 30 days. Data on the number of erythrocytes and haemoglobin in rat blood was analysed with LSD and to determine the optimum dosage was analysed by using regression test. Research results shown that the content of rambutan fruit peel extract may increase the number of erythrocytes and haemoglobin of blood. Conclusions from this research are the rambutan fruit peel extract at a dose of 45 mg/kg body weight can increase and maintain the number of erythrocytes and haemoglobin in the blood of rat exposed to cigarette smoke.

  16. Effect of Amygdalin on the Proliferation of Hyperoxia-exposed Type Ⅱ Alveolar Epithelial Cells Isolated from Premature Rat

    Institute of Scientific and Technical Information of China (English)

    祝华平; 常立文; 李文斌; 刘汉楚

    2004-01-01

    Summary: The pathogenesis of hyperoxia lung injury and the mechanism of amygdalin on type 2 alveolar epithelial cells (AEC2) isolated from premature rat lungs in vitro were investigated. AEC2 were obtained by primary culture from 20-days fetal rat lung and hyperoxia-exposed cell model was established. Cell proliferating viability was examined by MTT assay after treatment of amygdalin at various concentrations. DNA content and the proliferating cell nuclear antigen (PCNA) protein expression of AEC2 were measured by using flow cytometry and immunocytochemistry respectively after 24 h of hyperoxia exposure or amygdalin treatment. The results showed that hyperoxia inhibited the proliferation and decreased PCNA protein expression in AEC2 of premature rat in vitro. Amygdalin at the concentration range of 50-200 μmol/L stimulated the proliferation of AEC2 in a dose-dependent manner, however, 400 μmol/L amygdalin inhibited the proliferation of AEC2. Amygdalin at the concentration of 200 μmol/L played its best role in facilitating proliferation of AEC2s in vitro and could partially ameliorated the changes of proliferation in hyperoxia exposed AEC2 of premature rat. It has been suggested that hyperoxia inhibited the proliferation of AEC2s of premature rat, which may contribute to hyperoxia lung injury. Amygdalin may play partial protective role in hyperoxia-induced lung injury.

  17. Effect of amygdalin on the proliferation of hyperoxia-exposed type II alveolar epithelial cells isolated from premature rat.

    Science.gov (United States)

    Zhu, Huaping; Chang, Liwen; Li, Wenbin; Liu, Hanchu

    2004-01-01

    The pathogenesis of hyperoxia lung injury and the mechanism of amygdalin on type 2 alveolar epithelial cells (AEC2) isolated from premature rat lungs in vitro were investigated. AEC2 were obtained by primary culture from 20-days fetal rat lung and hyperoxia-exposed cell model was established. Cell proliferating viability was examined by MTT assay after treatment of amygdalin at various concentrations. DNA content and the proliferating cell nuclear antigen (PCNA) protein expression of AEC2 were measured by using flow cytometry and immunocytochemistry respectively after 24 h of hyperoxia exposure or amygdalin treatment. The results showed that hyperoxia inhibited the proliferation and decreased PCNA protein expression in A-EC2 of premature rat in vitro. Amygdalin at the concentration range of 50-200 micromol/L stimulated the proliferation of AEC2 in a dose-dependent manner, however, 400 micromol/L amygdalin inhibited the proliferation of AEC2. Amygdalin at the concentration of 200 micromol/L played its best role in facilitating proliferation of AEC2s in vitro and could partially ameliorated the changes of proliferation in hyperoxia exposed AEC2 of premature rat. It has been suggested that hyperoxia inhibited the proliferation of AEC2s of premature rat, which may contribute to hyperoxia lung injury. Amygdalin may play partial protective role in hyperoxia-induced lung injury.

  18. 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.

  19. 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.

  20. Antioxidant effects of calcium antagonists in rat brain homogenates.

    Science.gov (United States)

    Yao, K; Ina, Y; Nagashima, K; Ohmori, K; Ohno, T

    2000-06-01

    We studied the antioxidant activities of calcium antagonists against autoxidation in rat brain homogenates. The homogenates were incubated for 30 min at 37 degrees C with or without a calcium antagonist and subsequently assayed for lipid peroxide content. Percent inhibition of the lipid peroxidation was used as an index of the antioxidant effect. Dihydropyridine calcium antagonists exhibited concentration-dependent (3-300 micromol/l) inhibitory effects against lipid peroxidation. The relative order of antioxidant potency and associated IC50 values (micromol/l) of the calcium antagonists for inhibition of the lipid peroxidation were as follows: nifedipine (51.5)>barnidipine (58.6)>benidipine (71.2)>nicardipine (129.3)>amlodipine (135.5)>nilvadipine (167.3)>nitrendipine (252.1)> diltiazem (>300)=verapamil (>300). These results suggest that some dihydropyridine calcium antagonists show antioxidant properties. The antioxidant effects of the calcium antagonists may contribute to their pharmacological actions.

  1. Localization and labeling of rat brain in MR image based on Paxinos-Watson atlas

    Science.gov (United States)

    Cao, Jie; Cai, Chao; Ding, Mingyue; Zhou, Chengping

    2006-03-01

    Localization and labeling of function regions in brain is an important topic in experimental brain sciences because the huge amount of data collected by neuroscientists will become meaningless if we cannot give them a precise description of their locations. In this paper, we proposed a localization and labelling method of 3D MR image of rat brain based on Paxinos-Watson atlas. Our objective is to use the specific atlas to accomplish localization and labeling of specified tissue of interest (TOI) to mimic a veteran expert such that invisible or unclear anatomic function regions in the MR images of rat brain can be automatically identified and marked. We proposed a multi-step method to locate and label the TOIs from the MR image of rat brain. Firstly, pre-processing. It aims at the digitization and 3D reconstruction of the atlas and MRI of rat brain. Secondly, two-step registration. The global registration is to eliminate the big misalign and section angle offset as well as the scale between the MRI and atlas. We can choose some unambiguous and characteristic points manually, and based on these correspondences a coarse registration is obtained using affine model. The local registration is to address individual variability of rat brain that can be performed by using Snake model. Thirdly, post-processing. The goal is to locate and label the TOIs in the selected MR image of rat brain slice guided by well-registered atlas. The experiments demonstrated the feasibility of our method.

  2. Protective effect of taurine on the decreased biogenic amine neurotransmitter levels in the brain of mice exposed to arsenic.

    Science.gov (United States)

    Liu, Xiaohui; Piao, Fengyuan; Li, Yachen

    2013-01-01

    Arsenic (As) exposure has a toxic effect on the central nervous system, especially on learning and memory. Norepinephrine (NE), dopamine (DA), and serotonin (5-HT) play an important role in learning and memory function of the brain. In the present study, the protective effect of taurine on the disturbed biogenic amine neurotransmitter levels in the mouse brain induced by arsenic was examined. Sixty SPF mice were divided into three groups. The As exposure group was administered with 4 ppm As(2)O(3) through drinking water for 60 days. The protective group was treated with both 4 ppm As(2)O(3) and 150 mg/kg taurine. The control group was given drinking water alone. The levels of NE, DA, and 5-HT were determined by HPLC in the cerebrum and cerebellum of mice. Ultrastructure of synapses in brain tissue of mice was observed in these groups by transmission electron microscopy. The mRNA expressions of dopamine beta hydroxylase (DBH), tyrosine hydroxylase (TH), and tryptophan hydroxylase (TPH) as NE, DA, and 5-HT synzymes were also analyzed by real-time RT-PCR. The results showed that the concentrations of NE, DA, and 5-HT; the number of synaptic vesicles; and the expressions of TH, TPH, and DBH genes in the brains of mice exposed to As alone were significantly decreased. However, administration of taurine significantly alleviated the toxic effect on biochemicals detected in the experiment, compared with that in the brain of mice exposed to As alone. These results indicated that taurine was effective in counteracting the decreased biogenic amine neurotransmitter level and the mRNA expressions of their synzymes induced by arsenic.

  3. Regional protein synthesis in rat brain following acute hemispheric ischemia.

    Science.gov (United States)

    Dienel, G A; Pulsinelli, W A; Duffy, T E

    1980-11-01

    Regional protein synthesis was measured in rat brain at intervals up to 48 h following occlusion of the four major arteries to the brain for either 10 or 30 min. Four-vessel occlusions produces ischemia in the cerebral hemispheres and oligemia in the midbrain-diencephalon and brainstem. During the hour following 10 min of ischemia, protein synthesis, measured by incorporation of [14C]valine into protein, was inhibited in the cerebral cortex by 67%. Normal rates of protein synthesis were attained within 4 h of recirculation. In rats subjected to 30 min of ischemia, protein synthesis was inhibited by 83% during the first hour of recirculation in the cortex, caudate-putamen, and hippocampus. Recovery of protein synthesis in these regions was slow (25-48 h). The midbrain-diencephalon showed less inhibition, 67%, and faster recovery (by 12 h). Protein synthesis was unaffected in the brainstem. [14C]Autoradiography revealed that the pyramidal neurons of the hippocampus and areas of the caudate and cortex failed to recover normal rates of protein synthesis even after 48 h. The accumulation of TCA-soluble [14C]valine was enhanced (55-65%) in the cortex, caudate, and hippocampus after 30 min of ischemia; the increase persisted for 12 h. A smaller rise in [14C]valine content (30%) and more rapid normalization of valine accumulation (by 7 h) were observed in the midbrain-diencephalon; no changes were found in the brainstem. In the cortex, recovery was more rapid when the duration of ischemia was reduced. Thus, the degree of inhibition of protein synthesis, the accumulation of valine in the tissue, and the length of time required to reestablish normal values for these processes were dependent on both the severity and the duration of the ischemic insult. Restoration of normal rates of protein synthesis after ischemia was slow compared with the normalization of cerebral energy metabolites.

  4. Antioxidant effects of Dendropanax morbifera Léveille extract in the hippocampus of mercury-exposed rats

    OpenAIRE

    2015-01-01

    Background Dendropanax morbifera Léveille has been employed for the treatment of infectious diseases using folk medicine. In this study, we evaluated the antioxidant effects of a leaf extract of Dendropanax morbifera Léveille in the hippocampus of mercury-exposed rats. Methods Seven-week-old Sprague–Dawley rats received a daily intraperitoneal injection of 5 μg/kg dimethylmercury and/or oral Dendropanax morbifera Léveille leaf extract (100 mg/kg) for 4 weeks. Animals were sacrificed 2 h after...

  5. 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.

  6. 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.

  7. Protocatechuic acid protects brain mitochondrial function in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Semaming, Yoswaris; Sripetchwandee, Jirapas; Sa-Nguanmoo, Piangkwan; Pintana, Hiranya; Pannangpetch, Patchareewan; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2015-10-01

    Brain mitochondrial dysfunction has been demonstrated in diabetic animals with neurodegeneration. Protocatechuic acid (PCA), a major metabolite of anthocyanin, has been shown to exert glycemic control and oxidative stress reduction in the heart. However, its effects on oxidative stress and mitochondrial function in the brain under diabetic condition have never been investigated. We found that PCA exerted glycemic control, attenuates brain mitochondrial dysfunction, and contributes to the prevention of brain oxidative stress in diabetic rats.

  8. Rat brain aryl acylamidase: further characterization of multiple forms.

    Science.gov (United States)

    Hsu, L L; Halaris, A E; Freedman, D X

    1982-01-01

    1. Two fractions of aryl acylamidase (EC 3.5.1.13) were further separated from rat brain extracts at pH 7.5 by ammonium sulfate precipitation and Bio-Gel chromatography. 2. 1,2,3,4-Tetrahydro-beta-carboline competitively inhibited (67%) fraction-1 but slightly inhibited (13%) fraction-2. Tetrahydroharman, 6-hydroxy-tetrahydroharman and harminic acid slightly inhibited both fractions. Harmalol inhibited fraction-1 but enhanced fraction-2. 6-Methoxy-harman, 6-methoxy-harmalan and harmaline enhanced both fractions. 3. Pargyline did not affect either fraction. Methiothepin, cyproheptadine and chlorimipramine inhibited fraction-1 but stimulated fraction-2. 4. Neostigmine moderately (30%) inhibited AAA-2 but did not have any significant effect on AAA-1. 5. These results indicate that the beta-carboline compounds might play a role in regulating activity of AAA-1 and 2 in brain. 6. Both fractions might be related to serotonergic neurons but only AAA-2 might be associated with acetylcholinesterase.

  9. Effect of ethanol on enkephalinergic opioid system of rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Belyayev, N.A.; Balakireva, N.N.; Brusov, O.S.; Panchenko, L.F.

    1983-10-13

    Specific binding of /sup 3/H-morphine and /sup 3/H-(D-Ala/sup 2/, D-Leu/sup 5/)-enkephalin (H-EN) with opiatic receptors was studied on white rats along with the content of Met- and Leu-enkephalin and the activity of enkephalinase in various brain segments after single dose (20% solution in 0.9% NaCl, IP; 1.5-4.5 g/kg body weight) and chronic injection (20% EtOH substituted for drinking water) of ethanol. The single injection of EtOH (1.5-4.5 g/kg) resulted in a depression of the specific binding of H-EN with opiate receptors. Doses of 1.5 and 2.5 g/kg led to a lower content of Leu-enkephalin in mid-brain but to an increase of Met-enkephalin; the 4.5 g/kg dose had no effect on the striatum. With chronic administration of EtOH, most of the values obtained on the experimental animals were similar to the control data. 23 references.

  10. 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.

  11. Are soluble and membrane-bound rat brain acetylcholinesterase different

    Energy Technology Data Exchange (ETDEWEB)

    Andres, C.; el Mourabit, M.; Stutz, C.; Mark, J.; Waksman, A. (Centre de Neurochimie du C.N.R.S., Strasbourg, (France))

    1990-11-01

    Salt-soluble and detergent-soluble acetylcholinesterases (AChE) from adult rat brain were purified to homogeneity and studied with the aim to establish the differences existing between these two forms. It was found that the enzymatic activities of the purified salt-soluble AChE as well as the detergent-soluble AChE were dependent on the Triton X-100 concentration. Moreover, the interaction of salt-soluble AChE with liposomes suggests amphiphilic behaviour of this enzyme. Serum cholinesterase (ChE) did not bind to liposomes but its activity was also detergent-dependent. Detergent-soluble AChE remained in solution below critical micellar concentrations of Triton X-100. SDS polyacrylamide gel electrophoresis of purified, Biobeads-treated and iodinated detergent-soluble 11 S AChE showed, under non reducing conditions, bands of 69 kD, 130 kD and greater than 250 kD corresponding, respectively, to monomers, dimers and probably tetramers of the same polypeptide chain. Under reducing conditions, only a 69 kD band was detected. It is proposed that an amphiphilic environment stabilizes the salt-soluble forms of AChE in the brain in vivo and that detergent-soluble Biobeads-treated 11 S AChE possess hydrophobic domain(s) different from the 20 kD peptide already described.

  12. A STUDY OF FISCHER 344 RATS EXPOSED TO SILICA DUST FOR SIX MONTHS AT CONCENTRATIONS OF 0, 2, 10 OR 20 MG / M3.

    Energy Technology Data Exchange (ETDEWEB)

    KUTZMAN,R.S.

    1984-02-01

    The major objective of this study was to relate the results of a series of functional tests to the compositional and structural alterations in the rat lung induced by subchronic exposure to silica dust. Fischer-344 rats were exposed for 6 hours/day, 5 days/week for 6 months to either 0, 2, 10, or 20 mg SiO{sub 2}/m{sup 3}. The general appearance of the exposed rats was not different from that of the controls. Interestingly, female rats exposed to silica dust, at all tested concentrations, gained more weight than the controls. The lung weight and the lung-to-body weight ratio was greater in the male rats exposed to the highest concentration of silica dust.

  13. Brain Metabolic Changes in Rats following Acoustic Trauma

    Science.gov (United States)

    He, Jun; Zhu, Yejin; Aa, Jiye; Smith, Paul F.; De Ridder, Dirk; Wang, Guangji; Zheng, Yiwen

    2017-01-01

    Acoustic trauma is the most common cause of hearing loss and tinnitus in humans. However, the impact of acoustic trauma on system biology is not fully understood. It has been increasingly recognized that tinnitus caused by acoustic trauma is unlikely to be generated by a single pathological source, but rather a complex network of changes involving not only the auditory system but also systems related to memory, emotion and stress. One obvious and significant gap in tinnitus research is a lack of biomarkers that reflect the consequences of this interactive “tinnitus-causing” network. In this study, we made the first attempt to analyse brain metabolic changes in rats following acoustic trauma using metabolomics, as a pilot study prior to directly linking metabolic changes to tinnitus. Metabolites in 12 different brain regions collected from either sham or acoustic trauma animals were profiled using a gas chromatography mass spectrometry (GC/MS)-based metabolomics platform. After deconvolution of mass spectra and identification of the molecules, the metabolomic data were processed using multivariate statistical analysis. Principal component analysis showed that metabolic patterns varied among different brain regions; however, brain regions with similar functions had a similar metabolite composition. Acoustic trauma did not change the metabolite clusters in these regions. When analyzed within each brain region using the orthogonal projection to latent structures discriminant analysis sub-model, 17 molecules showed distinct separation between control and acoustic trauma groups in the auditory cortex, inferior colliculus, superior colliculus, vestibular nucleus complex (VNC), and cerebellum. Further metabolic pathway impact analysis and the enrichment overview with network analysis suggested the primary involvement of amino acid metabolism, including the alanine, aspartate and glutamate metabolic pathways, the arginine and proline metabolic pathways and the purine

  14. Cordycepin attenuates traumatic brain injury-induced impairments of blood-brain barrier integrity in rats.

    Science.gov (United States)

    Yuan, Jing; Wang, Aihua; He, Yan; Si, Zhihua; Xu, Shan; Zhang, Shanchao; Wang, Kun; Wang, Dawei; Liu, Yiming

    2016-10-01

    Loss of blood-brain barrier (BBB) integrity is a downstream event caused by traumatic brain injury (TBI). BBB integrity is affected by certain physiological conditions, including inflammation and oxidative stress. Cordycepin is a susbtance with anti-inflammatory and anti-oxidative effects. Therefore, it is necessary to investigate whether cordycepin affects TBI-induced impairments of BBB integrity. Using TBI rats as the in vivo model and applying multiple techniques, including stroke severity evaluation, Evans blue assessment, quantitative real-time PCR, Western blotting and ELISA, we investigated the dose-dependent protective effects of cordycepin on the TBI-induced impairments of BBB integrity. Cordycepin treatment attenuated the TBI-induced impairments in a dose-dependent manner, and played a role in protecting BBB integrity. Cordycepin was able to alleviate TBI-induced loss of tight junction proteins zonula occludens protein-1 (ZO-1) and occludin, which are important for BBB integrity. Moreover, cordycepin suppressed pro-inflammatory factors, including IL-1β, iNOS, MPO and MMP-9, and promoted anti-inflammation-associated factors arginase 1 and IL-10. Furthermore, cordycepin inhibited NADPH oxidase (NOX) expression and activity following TBI, probably through NOX1, but not NOX2 and NOX4. Cordycepin has protective effects against brain damages induced by TBI. The protection of cordycepin on BBB integrity was probably achieved through recovery of tight junction proteins, inhibition of local inflammation, and prevention of NOX activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Calcium-activated potassium channels mediated blood-brain tumor barrier opening in a rat metastatic brain tumor model

    Directory of Open Access Journals (Sweden)

    Ong John M

    2007-03-01

    Full Text Available Abstract Background The blood-brain tumor barrier (BTB impedes the delivery of therapeutic agents to brain tumors. While adequate delivery of drugs occurs in systemic tumors, the BTB limits delivery of anti-tumor agents into brain metastases. Results In this study, we examined the function and regulation of calcium-activated potassium (KCa channels in a rat metastatic brain tumor model. We showed that intravenous infusion of NS1619, a KCa channel agonist, and bradykinin selectively enhanced BTB permeability in brain tumors, but not in normal brain. Iberiotoxin, a KCa channel antagonist, significantly attenuated NS1619-induced BTB permeability increase. We found KCa channels and bradykinin type 2 receptors (B2R expressed in cultured human metastatic brain tumor cells (CRL-5904, non-small cell lung cancer, metastasized to brain, human brain microvessel endothelial cells (HBMEC and human lung cancer brain metastasis tissues. Potentiometric assays demonstrated the activity of KCa channels in metastatic brain tumor cells and HBMEC. Furthermore, we detected higher expression of KCa channels in the metastatic brain tumor tissue and tumor capillary endothelia as compared to normal brain tissue. Co-culture of metastatic brain tumor cells and brain microvessel endothelial cells showed an upregulation of KCa channels, which may contribute to the overexpression of KCa channels in tumor microvessels and selectivity of BTB opening. Conclusion These findings suggest that KCa channels in metastatic brain tumors may serve as an effective target for biochemical modulation of BTB permeability to enhance selective delivery of chemotherapeutic drugs to metastatic brain tumors.

  16. A simple implantation method for flexible, multisite microelectrodes into rat brains

    Directory of Open Access Journals (Sweden)

    Anja eRichter

    2013-07-01

    Full Text Available A long term functional and reliable coupling between neural tissue and implanted microelectrodes is the key issue in acquiring neural electrophysiological signals or therapeutically excite neural tissue. The currently often used rigid micro-electrodes are thought to cause a severe foreign body reaction resulting in a thick glial scar and consequently a poor tissue-electrode coupling in the chronic phase. We hypothesize, that this adverse effect might be remedied by probes compliant to the soft brain tissue, i.e. replacing rigid electrodes by flexible ones. Unfortunately, this flexibility comes at the price of a low stiffness, which makes targeted low trauma implantation very challenging. In this study, we demonstrate an adaptable and simple method to implant extremely flexible microprobes even to deep areas of rat’s brain. Implantation of flexible probes is achieved by rod supported stereotactic insertion fostered by a hydrogel (2% agarose in PBS cushion on the exposed skull. We were thus able to implant very flexible micro-probes in 70 rats as deep as the rodent's subthalamic nucleus. This work describes in detail the procedures and steps needed for minimal invasive, but reliable implantation of flexible probes.

  17. Effect of Alpha-Particle Irradiation on Brain Glycogen in the Rat

    Science.gov (United States)

    Wolfe, L. S.; Klatzo, Igor; Miquel, Jaime; Tobias, Cornelius; Haymaker, Webb

    1962-01-01

    The studies of Klatzo, Miquel, Tobias and Haymaker (1961) have shown that one of the earliest and most sensitive indications of the effects of alpha-particle irradiation on rat bran is the appearance of glycogen granules mainly in the neuroglia of the exposed area of the brain. Periodic acid-Schiff (PAS) positive, alpha-amylase soluble granules were demonstrated within 12 hr after irradiation, preceding by approximately 36 hr the first microscopically detectable vascular permeability disturbances, as shown by the fluorescein labeled serum protein technique. These studies suggested that the injurious effects of alpha-particle energy were on cellular elements primarily, according to the physical properties and distribution of the radiation in the tissue, and that the vascular permeability disturbances played a secondary role in pathogenesis. The purpose of this study was to correlate the histochemical observations on glycogen with a quantitative assessment of the glycogen in the irradiated brain tissue. It is felt that such a study may contribute to the understanding of radiation injury at the molecular level. A practical aspect of this problem is that the information on biological radiation effects due to accelerated particles from the cyclotron source, is employed in this study, is applicable to radiation from cosmic particles both in free space and entrapped in the Van Allen belts.

  18. Brain lipids in rats fed a diet supplemented with hen eggs of modified lipid content

    Directory of Open Access Journals (Sweden)

    Hodžić Aida

    2012-01-01

    Full Text Available The aim of this study was to research the impact of a diet supplemented with egg yolks of modified content, having in mind the type of fat added to the laying hens diet, on the brain lipids and their fatty acid composition in rats. During four weeks of the experiment, 64 Wistar rats, divided into four groups of 16 animals each (eight animals of both sexes, were fed the commercial rat feed (group C, or the feed that contained 70% of the commercial rat feed and 30% of freshly boiled yolks from the eggs originating from laying hens fed with 3% fish oil (group F, 3% palm olein (group P or 3% lard (group L. Concentration and content of total lipids and total cholesterol, as well as the fatty-acid composition of the total brain lipids were determined in the lipid extracts of the rats brains. Under unfavourable conditions, which in our case could be high dietary intake of the total fat due to egg yolk addition, the amount of total fat in the brain tissue or the mass of the organ itself can be changed. Applied dietary treatments could also influence the level of de novo synthesis of total cholesterol in the rat brain. High dietary fat intake, as well as the fat quality regarding its fatty acid composition, appear to be able to significantly influence the fatty acid profile of the total brain lipids in adult rats, whereas the level and quality of the changes also depend on sex.

  19. Garlic extract attenuates brain mitochondrial dysfunction and cognitive deficit in obese-insulin resistant rats.

    Science.gov (United States)

    Pintana, Hiranya; Sripetchwandee, Jirapas; Supakul, Luerat; Apaijai, Nattayaporn; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-12-01

    Oxidative stress in the obese-insulin resistant condition has been shown to affect cognitive as well as brain mitochondrial functions. Garlic extract has exerted a potent antioxidant effect. However, the effects of garlic extract on the brain of obese-insulin resistant rats have never been investigated. We hypothesized that garlic extract improves cognitive function and brain mitochondrial function in obese-insulin resistant rats induced by long-term high-fat diet (HFD) consumption. Male Wistar rats were fed either normal diet or HFD for 16 weeks (n = 24/group). At week 12, rats in each dietary group received either vehicle or garlic extract (250 and 500 mg·kg(-1)·day(-1)) for 28 days. Learning and memory behaviors, metabolic parameters, and brain mitochondrial function were determined at the end of treatment. HFD led to increased body weight, visceral fat, plasma insulin, cholesterol, and malondialdehyde (MDA) levels, indicating the development of insulin resistance. Furthermore, HFD rats had cognitive deficit and brain mitochondrial dysfunction. HFD rats treated with both doses of garlic extract had decreased body weight, visceral fat, plasma cholesterol, and MDA levels. Garlic extract also improved cognitive function and brain mitochondrial function, which were impaired in obese-insulin resistant rats caused by HFD consumption.

  20. 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.

  1. 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.

  2. Ethylene oxide in blood of ethylene-exposed B6C3F1 mice, Fischer 344 rats, and humans.

    Science.gov (United States)

    Filser, Johannes Georg; Kessler, Winfried; Artati, Anna; Erbach, Eva; Faller, Thomas; Kreuzer, Paul Erich; Li, Qiang; Lichtmannegger, Josef; Numtip, Wanwiwa; Klein, Dominik; Pütz, Christian; Semder, Brigitte; Csanády, György András

    2013-12-01

    The gaseous olefin ethylene (ET) is metabolized in mammals to the carcinogenic epoxide ethylene oxide (EO). Although ET is the largest volume organic chemical worldwide, the EO burden in ET-exposed humans is still uncertain, and only limited data are available on the EO burden in ET-exposed rodents. Therefore, EO was quantified in blood of mice, rats, or 4 volunteers that were exposed once to constant atmospheric ET concentrations of between 1 and 10 000 ppm (rodents) or 5 and 50 ppm (humans). Both the compounds were determined by gas chromatography. At ET concentrations of between 1 and 10 000 ppm, areas under the concentration-time curves of EO in blood (µmol × h/l) ranged from 0.039 to 3.62 in mice and from 0.086 to 11.6 in rats. At ET concentrations ≤ 30 ppm, EO concentrations in blood were 8.7-fold higher in rats and 3.9-fold higher in mice than that in the volunteer with the highest EO burdens. Based on measured EO concentrations, levels of EO adducts to hemoglobin and lymphocyte DNA were calculated for diverse ET concentrations and compared with published adduct levels. For given ET exposure concentrations, there were good agreements between calculated and measured levels of adducts to hemoglobin in rats and humans and to DNA in rats and mice. Reported hemoglobin adduct levels in mice were higher than calculated ones. Furthermore, information is given on species-specific background adduct levels. In summary, the study provides most relevant data for an improved assessment of the human health risk from exposure to ET.

  3. Haematological, Biochemical and Antioxidant Changes in Wistar Rats Exposed to Dichlorvos Based Insecticide Formulation Used in Southeast Nigeria

    Directory of Open Access Journals (Sweden)

    Kingsley C. Kanu

    2016-11-01

    Full Text Available The indiscriminate use of pesticide is a treat to non-target organisms. This study evaluates the haematological and biochemical changes induced by inhalation of local Nigerian dichlorvos insecticide on rats. The rats were randomly assigned to a control group which received only food and water and a test group which, in addition to food and water, was exposed to the pesticide for a period of 4 h daily for 28 days, after which exposure was discontinued for seven days. Five animals were sacrificed from each group on days 1, 7, 14, 21, 28 and 35, and blood was collected by cardiac puncture for haematological, biochemical and antioxidant analysis. Results obtained showed lowered values of red blood cell count (RBC, packed cell volume (PCV, haemoglobin, mean cell haemoglobin (MCH and mean cell haemoglobin concentration (MCHC (p < 0.05 with increased white blood cell count (WBC and platelet counts after day 14 when compared to the control group. Liver enzymes aspartate amino transaminase (AST and alanine amino transaminase (ALT were higher in the exposed rats compared to the control group (p < 0.05. Urea and creatinine concentrations increased significantly after day 1 and at day 28, while superoxide dismutase (SOD, gluthathione (GSH and catalase (CAT activity increased significantly compared to the control after day 1, day 14 and day 21, respectively. The RBC, PCV and haemoglobin values of all exposed rats were restored to normal following withdrawal of the pesticide, though AST, ALT, urea, creatinine and, glutathione values remained significantly high compared to the control. Inhalation of the local insecticide is toxic to the blood, liver and kidney of laboratory rats and may be deleterious to human health following long-term exposure.

  4. Hypothalamic-pituitary adrenal (HPAA) axis function in adult Fischer-344 rats exposed during development to neurotoxic chemicals perinatally.

    Science.gov (United States)

    Rosecrans, J A; Johnson, J H; Tilson, H A; Hong, J S

    1984-01-01

    The major objective of these experiments was to determine long-term effects on the hypothalamic-pituitary adrenal axis (HPAA) of adult rats exposed during development to chlordecone, an organochlorine insecticide. Chlordecone was administered to mothers prenatally plus the first 12 days of the neonatal period (6 ppm in the diet) or neonatally via a single subcutaneous injection to rats at 4 days of age (1 mg/pup in 20 micrograms of DMSO). DMSO (20 microliters/pup) and dexamethasone (100 micrograms/pup in 20 microliters saline) were also injected on day 4. HPAA function was evaluated at 70-80 days of age. Responsiveness of the HPAA to a repeated stressor was evaluated by exposing rats of each treatment group to a 7-day stress-induced analgesia (SIA) paradigm consisting of a daily 15 sec foot-shock (0.9 mA) exposure which was preceded by a 15 sec white noise conditioned stimulus. The behavioral response to daily stress was evaluated by measuring tail-flick latencies immediately before and/or after each stress exposure. The conditioned response to stress was evaluated 24 hours after the last of 7 daily foot-shock sessions in which rats of each treatment and experimental group were exposed to the shock chamber only. All rats were killed 15 minutes after the final session and tissue (serum and adrenals) were removed and frozen for later chemical analysis; serum and adrenal corticosterone (CS) and serum prolactin (Prl) levels were measured. Perinatal exposure to chlordecone did not significantly alter the behavioral and/or neuroendocrine responses to stress. Ambient hormone levels (both CS and Prl), however, were uniformly attenuated by chlordecone.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    OpenAIRE

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

    2007-01-01

    The blood–brain barrier (BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P-glycoprotein (P-gp), expressed on brain capillary endothelial cells, is part of the BBB. P-gp expression on capillary endothelium decreases 5 days after brain irradiation, which may reduce P-gp function and increase brain levels of P-gp substrates. To elucidate whether radiation therapy reduces P-gp expression and function in the brain, right hemispheres of rats wer...

  6. Yawning and stretching predict brain temperature changes in rats:Support for the thermoregulatory hypothesis

    Directory of Open Access Journals (Sweden)

    Melanie L Shoup-Knox

    2010-09-01

    Full Text Available Recent research suggests that yawning is an adaptive behavior that functions to promote brain thermoregulation among homeotherms. To explore the relationship between brain temperature and yawning we implanted thermocoupled probes in the frontal cortex of rats to measure brain temperature before, during and after yawning. Temperature recordings indicate that yawns and stretches occurred during increases in brain temperature, with brain temperatures being restored to baseline following the execution of each of these behaviors. The circulatory changes that accompany yawning and stretching may explain some of the thermal similarities surrounding these events. These results suggest that yawning and stretching may serve to maintain brain thermal homeostasis.

  7. 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....

  8. Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain.

    Science.gov (United States)

    Duncan, Jeremy; Wang, Niping; Zhang, Xiao; Johnson, Shakevia; Harris, Sharonda; Zheng, Baoying; Zhang, Qinli; Rajkowska, Grazyna; Miguel-Hidalgo, Jose Javier; Sittman, Donald; Ou, Xiao-Ming; Stockmeier, Craig A; Wang, Jun Ming

    2015-07-01

    Major depressive disorder and alcoholism are significant health burdens that can affect executive functioning, cognitive ability, job responsibilities, and personal relationships. Studies in animal models related to depression or alcoholism reveal that the expression of Krüppel-like factor 11 (KLF11, also called TIEG2) is elevated in frontal cortex, which suggests that KLF11 may play a role in stress- or ethanol-induced psychiatric conditions. KLF11 is a transcriptional activator of monoamine oxidase A and B, but also serves other functions in cell cycle regulation and apoptotic cell death. In the present study, immunohistochemistry was used to quantify intensity of nuclear KLF11, combined with an unbiased stereological approach to assess nuclei in fronto-limbic, limbic, and other brain regions of rats exposed chronically to social defeat or ethanol. KLF11 immunoreactivity was increased significantly in the medial prefrontal cortex, frontal cortex, and hippocampus of both stressed rats and rats fed ethanol. However, expression of KLF11 protein was not significantly affected in the thalamus, hypothalamus, or amygdala in either treatment group compared to respective control rats. Triple-label immunofluorescence revealed that KLF11 protein was localized in nuclei of neurons and astrocytes. KLF11 was also co-localized with the immunoreactivity of cleaved caspase-3. In addition, Western blot analysis revealed a significant reduction in anti-apoptotic protein, Bcl-xL, but an increase of caspase-3 expression in the frontal cortex of ethanol-treated rats compared to ethanol-preferring controls. Thus, KLF11 protein is up-regulated following chronic exposure to stress or ethanol in a region-specific manner and may contribute to pro-apoptotic signaling in ethanol-treated rats. Further investigation into the KLF11 signaling cascade as a mechanism for neurotoxicity and cell death in depression and alcoholism may provide novel pharmacological targets to lessen brain damage and

  9. [Study of distribution of protein of the spine apparatus synaptopodin in cortical brain parts of rats submitted to hypoxia at different periods of embryogenesis].

    Science.gov (United States)

    Vasil'ev, D S; Tumanova, N L; Zhuravin, I A

    2010-01-01

    A comparative study of the nervous tissue and distribution of the spine apparatus protein synaptopodin was performed in all layers of the brain sensorymotor cortex and hippocampal CA1 area in control rats and in the rats submitted to hypoxia at E14 and E18. It was found that beginning from the 20th day of postnatal development, in rats submitted to hypoxia both at E14 and E18 there was observed a statistically significant decrease of the mean number of labile synaptopodin-positive spines in the stratum radiatum molecular of the hippocampus area CA1. The decrease of the number of labile spines in the sensorymotor brain cortex was revealed only in the I layer beginning from the 20th day after birth in the rats submitted to hypoxia at E14. Maximal differences in the studied brain areas were observed in adult rats (exposed to hypoxia at E14: in the neocortex--a decrease by 23 +/- 10%, in hippocampus--by 24 +/- 8%, respectively). In adult animals, the increased degeneration of neuzons was not detected. It is suggested that disturbances in cognitive functions and in the capability for learning observed in rats after prenatal hypoxia can be due to a decrease of the amount of the labile synaptopodin-positive spines, which leads to a change of the structural-functional properties of neuronal networks and to a decrease of their plasticity.

  10. Neuroprotective peptide ADNF-9 in fetal brain of C57BL/6 mice exposed prenatally to alcohol

    Directory of Open Access Journals (Sweden)

    Karty Jonathan A

    2011-10-01

    Full Text Available Abstract Background A derived peptide from activity-dependent neurotrophic factor (ADNF-9 has been shown to be neuroprotective in the fetal alcohol exposure model. We investigated the neuroprotective effects of ADNF-9 against alcohol-induced apoptosis using TUNEL staining. We further characterize in this study the proteomic architecture underlying the role of ADNF-9 against ethanol teratogenesis during early fetal brain development using liquid chromatography in conjunction with tandem mass spectrometry (LC-MS/MS. Methods Pregnant C57BL/6 mice were exposed from embryonic days 7-13 (E7-E13 to a 25% ethanol-derived calorie [25% EDC, Alcohol (ALC] diet, a 25% EDC diet simultaneously administered i.p. ADNF-9 (ALC/ADNF-9, or a pair-fed (PF liquid diet. At E13, fetal brains were collected from 5 dams from each group, weighed, and frozen for LC-MS/MS procedure. Other fetal brains were fixed for TUNEL staining. Results Administration of ADNF-9 prevented alcohol-induced reduction in fetal brain weight and alcohol-induced increases in cell death. Moreover, individual fetal brains were analyzed by LC-MS/MS. Statistical differences in the amounts of proteins between the ALC and ALC/ADNF-9 groups resulted in a distinct data-clustering. Significant upregulation of several important proteins involved in brain development were found in the ALC/ADNF-9 group as compared to the ALC group. Conclusion These findings provide information on potential mechanisms underlying the neuroprotective effects of ADNF-9 in the fetal alcohol exposure model.

  11. Hypertension and Cardiovascular Remodelling in Rats Exposed to Continuous Light: Protection by ACE-Inhibition and Melatonin

    Directory of Open Access Journals (Sweden)

    Fedor Simko

    2014-01-01

    Full Text Available Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old male Wistar rats (10 per group were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100 mg/kg/day or melatonin (10 mg/kg/day. Exposure to continuous light led to hypertension, left ventricular (LV hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LV hypertrophy development and only melatonin reduced LV hydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease.

  12. L-citrulline supplementation reverses the impaired airway relaxation in neonatal rats exposed to hyperoxia

    Directory of Open Access Journals (Sweden)

    Sopi Ramadan B

    2012-08-01

    Full Text Available Abstract Background Hyperoxia is shown to impair airway relaxation via limiting L-arginine bioavailability to nitric oxide synthase (NOS and reducing NO production as a consequence. L-arginine can also be synthesized by L-citrulline recycling. The role of L-citrulline supplementation was investigated in the reversing of hyperoxia-induced impaired relaxation of rat tracheal smooth muscle (TSM. Methods Electrical field stimulation (EFS, 2–20 V-induced relaxation was measured under in vitro conditions in preconstricted tracheal preparations obtained from 12 day old rat pups exposed to room air or hyperoxia (>95% oxygen for 7 days supplemented with L-citrulline or saline (in vitro or in vivo. The role of the L-citrulline/L-arginine cycle under basal conditions was studied by incubation of preparations in the presence of argininosuccinate synthase (ASS inhibitor [α-methyl-D, L-aspartate, 1 mM] or argininosuccinate lyase inhibitor (ASL succinate (1 mM and/or NOS inhibitor [Nω-nitro-L-arginine methyl ester; 100 μM] with respect to the presence or absence of L-citrulline (2 mM. Results Hyperoxia impaired the EFS-induced relaxation of TSM as compared to room air control (p ; 0.5 ± 0.1% at 2 V to 50.6 ± 5.7% at 20 V in hyperoxic group: 0.7 ± 0.2 at 2 V to 80.0 ± 5.6% at 20 V in room air group. Inhibition of ASS or ASL, and L-citrulline supplementation did not affect relaxation responses under basal conditions. However, inhibition of NOS significantly reduced relaxation responses (p in vivo and in vitro also reversed the hyperoxia-impaired relaxation. The differences were significant (p ; 0.8 ± 0.3% at 2 V to 47.1 ± 4.1% at 20 V without L-citrulline; 0.9 ± 0.3% at 2 V to 68.2 ± 4.8% at 20 V with L-citrulline. Inhibition of ASS or ASL prevented this effect of L-citrulline. Conclusion The results indicate the presence of an L-citrulline/L-arginine cycle in the airways of rat pups

  13. Protein-energy malnutrition during pregnancy alters caffeine's effect on brain tissue of neonate rats.

    Science.gov (United States)

    Mori, M; Wilber, J F; Nakamoto, T

    1984-12-17

    We studied whether protein-energy malnutrition changed brain susceptibility to a small dose of caffeine in newborn rats. Since we had demonstrated previously that caffeine intake during lactation increased the brain neuropeptide on newborns, we investigated further the effects of the prenatal administration of caffeine on TRH and cyclo (His-Pro). From day 13 of gestation to delivery day, pregnant rats in one group were fed either a 20% or a 6% protein diet ad libitum, and those in the other group were pair-fed with each protein diet supplemented with caffeine at an effective dose of 2 mg/100 g body weight. Upon delivery, brain weight, brain protein, RNA, DNA and the neuropeptides thyrotropin-releasing hormone (TRH) and cyclo (His-Pro) were measured in the newborn rats. A 6% protein without caffeine diet caused reductions in brain weights and brain protein, RNA and DNA contents, but did not alter brain TRH and cyclo (His-Pro) concentrations in the newborn animals. In the offspring from dams fed a 6% protein diet, caffeine administration significantly elevated brain weights and brain contents of protein, RNA and DNA. In contrast, these values were similar between noncaffeine and caffeine-supplemented animals in a 20% protein diet group. Brain TRH and cyclo (His-Pro) concentrations were not changed by caffeine administration. These data suggest that caffeine augments protein synthesis in the newborn rat brain when malnourished, but that the same dose of caffeine did not affect protein synthesis in brains of newborn rats from normally nourished dams. Therefore, the present findings indicate that the nutritional status of mothers during pregnancy has important implication in the impact of caffeine on their offspring's brains.

  14. Timing of intervention affects brain electrical activity in children exposed to severe psychosocial neglect.

    Directory of Open Access Journals (Sweden)

    Ross E Vanderwert

    Full Text Available BACKGROUND: Early psychosocial deprivation has profound effects on brain activity in the young child. Previous reports have shown increased power in slow frequencies of the electroencephalogram (EEG, primarily in the theta band, and decreased power in higher alpha and beta band frequencies in infants and children who have experienced institutional care. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the consequences of removing infants from institutions and placing them into a foster care intervention on brain electrical activity when children were 8 years of age. We found the intervention was successful for increasing high frequency EEG alpha power, with effects being most pronounced for children placed into foster care before 24 months of age. CONCLUSIONS/SIGNIFICANCE: The dependence on age of placement for the effects observed on high frequency EEG alpha power suggests a sensitive period after which brain activity in the face of severe psychosocial deprivation is less amenable to recovery.

  15. Bcl-2 gene family expression in the brain of rat offspring after gestational and lactational dioxin exposure.

    Science.gov (United States)

    Chang, Shwu-Fen; Sun, Yu-Yo; Yang, Liang-Yo; Hu, Ssu-Yao; Tsai, Shih-Ying; Lee, Wen-Sen; Lee, Yi-Hsuan

    2005-05-01

    Recent epidemiological studies have shown that dioxin, a persistent organic pollutant, is related to cognitive and behavioral abnormalities in the offspring of exposed cohort. In order to investigate the possible impact of dioxin in survival gene expression during brain development, we established an animal model of gestational and lactational dioxin-exposed rat offspring. The expressions of dioxin-responsive gene cytochrome P450 1A1 (CYP1A1), apoptotic gene Bax, and anti-apoptotic genes Bcl-2 and Bcl-xL were examined in rat liver and brains using Western blot analysis and RT-PCR. The results showed that treatment of pregnant rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (2 microg/kg body weight through oral delivery) at gestation day 15 resulted in an increase of Bcl-xL in offspring male liver and cerebral cortex, but a decrease in female offspring. In contrast, the expression of Bcl-xL in the cerebellum was decreased in male, but increased in female. Bcl-2, another anti-apoptotic gene, was also downregulated in P0 female liver, cerebral cortex, but was not observed in male. In the 4-month-old offspring, however, the Bcl-2 protein levels in the liver and cerebellum of both male and female pups were higher in the TCDD group as compared with the control group. However, the Bcl-2 level in the cerebral cortex of TCDD-treated groups was higher than the control group only in female but not male offspring at 4 months old. The expression of Bax showed no significant changes upon TCDD exposure at P0 stage, but was significantly reduced in the 4-month-old male cortex. These results indicate that early exposure of dioxin could affect the development of certain brain regions with gender difference, in terms of its differential effect on expressions of Bcl-xL, Bcl-2, and Bax.

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

    Science.gov (United States)

    Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne; Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S; Simonsen, Mette; Ott, Peter; Vilstrup, Hendrik; Sørensen, Michael

    2014-03-01

    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)NH(4)(+) 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 of (15)NH(4)(+) into glutamine in all tissues. It did not affect alanine concentrations in any of the tissues but plasma alanine concentration increased; incorporation of (15)NH(4)(+) into alanine was increased in brain in sham and BDL rats and in kidney in sham rats. It inhibited GS in all tissues examined but only in brain was an increased incorporation of (15)N-ammonia into alanine observed. Liver and kidney were important for metabolizing blood-borne ammonia.

  17. Effect of ascorbic acid on fatigue of skeletal muscle fibres in long-term cold exposed Sprague Dawley rats.

    Science.gov (United States)

    Rashid, Aneeqa; Khan, Umar Ali; Ayub, Muhammad

    2011-01-01

    On exposure to prolonged cold temperature, the body responds for effective heat production both by shivering and non-shivering thermogenesis. Cold exposure increases the production of reactive oxygen species which influence the sarcoplasmic reticulum Ca++ release from the skeletal muscles and affect their contractile properties. The role of ascorbic acid supplementation on force of contraction during fatigue of cold exposed skeletal muscles was evaluated in this study. Ninety healthy, male Sprague Dawley rats were randomly divided into three groups of control (I), cold exposed (II), and cold exposed with ascorbic acid 500 mg/L supplementation mixed in drinking water (III). Group II and III were given cold exposure by keeping their cages in ice-filled tubs for 1 hr/day for one month. After one month, the extensor digitorum longus muscle was dissected out and force of contraction during fatigue in the skeletal muscle fibres was analysed on a computerised data acquisition system. The cold exposed group showed a significant delay in the force of contraction during fatigue of skeletal muscle fibres compared to control group. Group III showed easy fatigability and a better force of contraction than the cold exposed group. Ascorbic acid increases the force of contraction and decreases resistance to fatigue in the muscles exposed to chronic cold.

  18. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Changlian [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Gao, Jianfeng [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Department of Physiology, Henan Traditional Medical University (China); Li, Qian; Huang, Zhiheng; Zhang, Yu; Li, Hongfu [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Kuhn, Hans-Georg [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Blomgren, Klas, E-mail: klas.blomgren@neuro.gu.se [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatric Oncology, The Queen Silvia Children' s Hospital, Gothenburg (Sweden)

    2011-01-07

    Research highlights: {yields} The effect of MRI on the developing brain is a matter of debate. {yields} Repeated exposure to MRI did not affect neurogenesis. {yields} Memory function was not affected by repeated MRI during development. {yields} Neither late gestation nor young postnatal brains were affected by MRI. {yields} Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 {sup o}C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

  19. Effect of exposure and withdrawal of 900-MHz-electromagnetic waves on brain, kidney and liver oxidative stress and some biochemical parameters in male rats.

    Science.gov (United States)

    Ragy, Merhan Mamdouh

    2015-01-01

    Increasing use of mobile phones in daily life with increasing adverse effects of electromagnetic radiation (EMR), emitted from mobile on some physiological processes, cause many concerns about their effects on human health. Therefore, this work was designed to study the effects of exposure to mobile phone emits 900-MHz EMR on the brain, liver and kidney of male albino rats. Thirty male adult rats were randomly divided into four groups (10 each) as follows: control group (rats without exposure to EMR), exposure group (exposed to 900-MHz EMR for 1 h/d for 60 d) and withdrawal group (exposed to 900-MHz electromagnetic wave for 1 h/d for 60 d then left for 30 d without exposure). EMR emitted from mobile phone led to a significant increase in malondialdehyde (MDA) levels and significant decrease total antioxidant capacity (TAC) levels in brain, liver and kidneys tissues. The sera activity of alanine transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and corticosterone were significantly increased (p electromagnetic field emitting from mobile phone might produce impairments in some biochemicals changes and oxidative stress in brain, liver and renal tissue of albino rats. These alterations were corrected by withdrawal.

  20. Localization profile of Cathepsin L in the brain of African giant rat ...

    African Journals Online (AJOL)

    Localization profile of Cathepsin L in the brain of African giant rat ( Cricestomys gambianus ) ... Log in or Register to get access to full text downloads. ... Within the diencephalon high density of positive signals was observed in mediodorsal and ...

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

    Directory of Open Access Journals (Sweden)

    Retty Ratnawati

    2017-08-01

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

  2. 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.

  3. Changing Numbers of Neuronal and Non-Neuronal Cells Underlie Postnatal Brain Growth in the Rat

    National Research Council Canada - National Science Library

    Fabiana Bandeira; Roberto Lent; Suzana Herculano-Houzel; Jon H. Kaas

    2009-01-01

    .... To test this hypothesis, here we investigate quantitatively the postnatal changes in the total number of neuronal and non-neuronal cells in the developing rat brain, and examine how these changes...

  4. Beneficial effects of the sigma1 receptor agonists igmesine and dehydroepiandrosterone against learning impairments in rats prenatally exposed to cocaine.

    Science.gov (United States)

    Meunier, Johann; Maurice, Tangui

    2004-01-01

    In utero cocaine (IUC) exposure results in offspring rats in complex neurochemical and behavioral alterations, particularly affecting learning and memory processes. We examined here the impact of IUC exposure on memory functions in male and female offspring rats and report that selective sigma(1) (sigma(1)) receptor agonists are effective in reversing the deficits. Dams received a daily cocaine, 20 mg/kg ip, injection between gestational days E17 to E20. Learning was examined in offspring between day P30 and P41 using delayed alternation in the T-maze, water-maze learning and passive avoidance. Both male and female rats prenatally exposed to cocaine showed delayed alternation deficits and impairments of acquisition of a fixed platform position in the water maze, as shown by higher acquisition latencies and diminutions of time spent in the training quadrant during the probe test. The acquisition of a daily changing platform position also demonstrated impaired working memory. Finally, passive avoidance deficits were observed. Pretreatment with the synthetic sigma(1) agonist igmesine (0.1-1 mg/kg ip) or the neuroactive steroid dehydroepiandrosterone (DHEA 10-40 mg/kg ip) reversed the prenatal cocaine-induced learning deficits in offspring rats for each test. The sigma(1) antagonist BD1063 (1 mg/kg ip) failed to affect performances alone but blocked the igmesine and DHEA effects, confirming the involvement of the sigma(1) receptor. IUC exposure thus results in marked memory deficits, affecting spatial and nonspatial short- and long-term memories in juvenile male and female offspring rats. The activation of the sigma(1) neuromodulatory receptor allows a complete behavioral recovery of the memory functions in prenatally cocaine-exposed rats.

  5. Effects of chloramphenicol preconditioning on oxidative respiratory function of cerebral mitochondria in rats exposed to acute hypoxia

    Institute of Scientific and Technical Information of China (English)

    陈丽峰; 柳君泽; 党永明; 宋熔

    2004-01-01

    Objective: To investigate the roles of chloramphenicol (CAP) preconditioning in the oxidative respiratory function of cerebral mitochondria in rats exposed to acute hypoxia during acute hypoxia by observing the changes of mitochondrial oxidative respiratory function and cytochrome C oxidase (COX) activity. Methods: Adult male Wistar rats were randomly divided into 4 groups: control (C), medication (M), hypoxia (H), and medication plus hypoxia (MH). Rats in groups M and MH were administered by peritoneal injection of CAP (50 mg/kg) every 12 h for 7 d before decapitation, but those in groups H and MH were exposed to a hypobaric chamber simulating 5 000 m high altitude for 24 h. The rat cerebral cortex was removed and mitochondria were isolated by centrifugation. Mitochondrial respiratory function and COX activity were measured by Clark oxygen electrode. Results: Compared with Group C, Group H showed significantly elevated state 4respiration (ST4), decreased state 3 respiration (ST3), and respiratory control rate (RCR) in mitochondrial respiration during acute hypoxic exposure. ST3 in Group MH was significantly lower than that in Group C, but was not significantly different from that in Groups H and M, while ST4 in Group MH was significantly lower than that in groups C and H. RCR in Group MH was higher than that in Group H, but lower than that in Group C. COX activity in Group H was significantly lower than that in Group C. In Group MH, COX activity increased and was higher than that in Group H, but was still lower than that in Group C. Conclusion: Acute hypoxic exposure could lead to mitochondrial respiratory dysfunction, suggesting that CAP preconditioning might be beneficial to the recovery of rat respiratory finction. The change of COX activity is consistent with that of mitochondrial respiratory function during acute hypoxic exposure and CAP-administration, indicating that COX plays an important role in oxidative phosphorylation function of mitochondria from

  6. 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.

  7. Four weeks' inhalation exposure of Long Evans rats to 4-tert-butyltoluene: Effect on evoked potentials, behaviour and brain neurochemistry

    DEFF Research Database (Denmark)

    Lam, Henrik Rye; Ladefoged, Ole; Østergaard, Grete

    2000-01-01

    Long-lasting central nervous system (CNS) neurotoxicity of 4-tert-butyltoluene (TBT) has been investigated using electrophysiology, behaviour, and neurochemistry in Long Evans rats exposed by inhalation to 0, 20, or 40 p.p.m. TBT 6 hr/day, 7 days/week for 4 weeks. Flash evoked potentials...... and somatosensory evoked potentials were not affected by TBT In Auditory Brain Stem Response there was no shift in hearing threshold, but the amplitude of the first wave was increased in both exposed groups at high stimulus levels. Three to four months after the end of exposure, behavioural studies in Morris water...... maze and eight-arm maze failed to demonstrate any TBT induced effects. Exposure was followed by a 5 months exposure-free period prior to gross regional and subcellular (synaptosomal) neurochemical investigations of the brain. TBT reduced the NA concentration in whole brain minus cerebellum...

  8. Blast-induced moderate neurotrauma (BINT) elicits early complement activation and tumor necrosis factor α (TNFα) release in a rat brain.

    Science.gov (United States)

    Dalle Lucca, Jurandir J; Chavko, Mikulas; Dubick, Michael A; Adeeb, Saleena; Falabella, Michael J; Slack, Jessica L; McCarron, Richard; Li, Yansong

    2012-07-15

    Blast-induced neurotrauma (BINT) is a major medical concern yet its etiology is largely undefined. Complement activation may play a role in the development of secondary injury following traumatic brain injury; however, its role in BINT is still undefined. The present study was designed to characterize the complement system and adaptive immune-inflammatory responses in a rat model of moderate BINT. Anesthetized rats were exposed to a moderate blast (120 kPa) using an air-driven shock tube. Brain tissue injury, systemic and local complement, cerebral edema, inflammatory cell infiltration, and pro-inflammatory cytokine production were measured at 0.5, 3, 48, 72, 120, and 168 h. Injury to brain tissue was evaluated by histological evaluation. Systemic complement was measured via ELSIA. The remaining measurements were determined by immunohistoflourescent staining. Moderate blast triggers moderate brain injuries, elevated levels of local brain C3/C5b-9 and systemic C5b-9, increased leukocyte infiltration, unregulated tumor necrosis factor alpha (TNFα), and aquaporin-4 in rat brain cortex at 3- and 48-hour post blast. Early immune-inflammatory response to BINT involves complement and TNFα, which correlates with hippocampus and cerebral cortex damage. Complement and TNFα activation may be a novel therapeutic target for reducing the damaging effects of BINT inflammation.

  9. BRAIN VOLUMES OF THE LAMB, RAT AND BIRD DO NOT SHOW HEMISPHERIC ASYMMETRY: A STEREOLOGICAL STUDY

    Directory of Open Access Journals (Sweden)

    Bünyamin Sahin

    2011-05-01

    Full Text Available It is well known that there are functional differences between right and left brain hemispheres. However, it is not clear whether these functional differences are reflected in morphometric differences. This study was carried out to investigate the right-left asymmetry, and sex and species differences of the brains using the Cavalieri principle for volume estimation. Seventeen lambs, 10 rats and 12 avian brains were used to estimate brain volumes. A transparent point grid was superimposed on the slices of lamb brains directly and the slices of the rat and avian brains were projected onto a screen at 10x magnification. Surface areas of the cut slice faces were estimated by simply counting the points that hit the slices. Mean brain volumes were 37.74 cm3, 598.95 mm3 and 730.38 mm3 and the coefficients of variations were 0.08, 0.05 and 0.05 for lamb, rat and avian brains respectively. The differences between left and right hemispheres did not show statistical significance (P > 0.05. However, the male brain volumes were larger than the females for the lamb and bird (P < 0.05. In light of such findings, it will be necessary to evaluate neuron number of the brain hemispheres to provide more useful data regarding inter-hemispheric brain asymmetry.

  10. Fluoxetine induces changes in the testicle and testosterone in adult male rats exposed via placenta and lactation.

    Science.gov (United States)

    Monteiro Filho, Waldo Oliveira; de Torres, Sandra Maria; Amorim, Marleyne José Afonso Accioly Lins; Andrade, Anderson Joel Martino; de Morais, Rosana Nogueira; Tenorio, Bruno Mendes; da Silva Junior, Valdemiro Amaro

    2014-10-01

    Fluoxetine is a selective serotonin reuptake inhibitor used to treat depression in pregnant and nursing women. However, recent studies have shown adverse effects in the male reproductive system after fluoxetine treatment. Aiming to analyze the extent of damage caused by fluoxetine in the testicle and safe doses for treatment during the perinatal period, the present study analyzed the effects of in utero exposure and exposure during lactation to fluoxetine in spermatogenesis of male rat offspring in adulthood. Wistar rat dams were orally treated with fluoxetine (5, 10, and 20 mg/kg) from 13 days of gestation to lactation day 21 and their offspring were analyzed at 90 days old. Results showed a reduction in the weight of testes (16%), epididymis (28%), and seminal glands (18%) in animals exposed to fluoxetine 20 mg/kg compared to the control. Seminal gland weight was also reduced 25% and 30% in animals exposed to 5 mg/kg and 10 mg/kg fluoxetine, respectively. Body weight of animals exposed to 20 mg/kg fluoxetine was reduced from post-natal day 9 to 36 compared to controls but from the post-natal day 9 to 36 there was no statistical difference. The volume of seminiferous epithelium reduced 17% and the total volume of Leydig cells reduced 30% in the group exposed to fluoxetine at 20 mg/kg. Furthermore, Leydig cells volume reduced 29% in the 5 mg/kg group. The length of the seminiferous tubules reduced 17% and daily sperm production per testicle also reduced 18% in animals exposed to the highest dose of fluoxetine compared to controls. The individual area of Leydig cells increased 7% and plasma testosterone increased 49% in animals exposed to fluoxetine at 20 mg/kg. In conclusion, exposure to 20 mg/kg fluoxetine via the placenta and during lactation may change testosterone and testicular parameters important for sperm production and male fertility in adulthood.

  11. Oxidative stress is reduced in Wistar rats exposed to smoke from tobacco and treated with specific broad-band pulse electromagnetic fields

    Directory of Open Access Journals (Sweden)

    Bajić V.

    2009-01-01

    Full Text Available There have been a number of attempts to reduce the oxidative radical burden of tobacco. A recently patented technology, pulse electromagnetic technology, has been shown to induce differential action of treated tobacco products versus untreated products on the production of reactive oxygen species (ROS in vivo. In a 90-day respiratory toxicity study, Wistar rats were exposed to cigarette smoke from processed and unprocessed tobacco and biomarkers of oxidative stress were compared with pathohistological analysis of rat lungs. Superoxide dismutase (SOD activity was decreased in a dose-dependent manner to 81% in rats exposed to smoke from normal cigarettes compared to rats exposed to treated smoke or the control group. These results correspond to pathohistological analysis of rat lungs, in which those rats exposed to untreated smoke developed initial signs of emphysema, while rats exposed to treated smoke showed no pathology, as in the control group. The promise of inducing an improved health status in humans exposed to smoke from treated cigarettes merits further investigation.

  12. Characterization of rat brain NCAM mRNA using DNA oligonucleotide probes

    DEFF Research Database (Denmark)

    1990-01-01

    A number of different isoforms of the neural cell adhesion molecule (NCAM) have been identified. The difference between these is due to alternative splicing of a single NCAM gene. In rat brain NCAM mRNAs with sizes of 7.4, 6.7, 5.2, 4.3 and 2.9 kb have been reported. We have synthesized six DNA...... the five NCAM mRNAs in rat brain....

  13. 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.

  14. 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.

  15. Large litters rearing changes brain expression of GLUT3 and acetylcholinesterase activity in adult rats.

    Science.gov (United States)

    de Vasconcelos, Vivian Sarmento; Machado, Sonia Salgueiro; Guedes, Rubem Carlos Araújo; Bandeira, Bruno Carneiro; Ximenes-da-Silva, Adriana

    2012-09-06

    Effects of malnutrition in the brain are more pronounced during the period of growth spurt, corresponding to the suckling in rodents. Neuronal glucose transporter GLUT3 expression and acetylcholinesterase activity were studied in the brain of adult young rats (84 days old) suckled in litters formed by 6 (control group) or 12 pups (malnourished group). In the adult rats, brain weight, blood glucose levels and GLUT3 expression were decreased in malnourished group (5%, 18%, 58%, respectively, Pmalnutrition during suckling period decreased GLUT3 expression and increased acetylcholinesterase activity in the rat brain that could contribute to possible cognitive deficits and changes of brain metabolic activity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Acute treatment with 5-HT3 receptor antagonist, tropisetron, reduces immobility in intact female rats exposed to the forced swim test.

    Science.gov (United States)

    Bravo, Gabriela; Maswood, Sharmin

    2006-10-01

    The effects of tropisetron, a 5-HT3 receptor antagonist, were evaluated in adult Fischer female rats exposed to the Forced Swim Test (FST). Rats selected on the days of proestrus or estrus was immersed in a cylinder of water for 2 consecutive days. Rats were exposed to the FST for 15 min on day 1 (pretest), followed by a 5-min session (test), 24 h later. The proestrous-estrous group consisted of rats that were exposed to the FST on their proestrous stage (pretest); then 24 h later the same rats were exposed to the FST on their estrous stage (test). Rats in the estrous-diestrous group were exposed to the FST on their estrous stage (pretest) and 24 h later on their diestrous stage (test). Rats were injected intraperitoneally with saline or 1.0 or 2.0 mg/kg tropisetron 30 min prior to exposure to the cylinder on the test day. Immobility, swimming, and struggling behaviors were scored for 5 min. There was a significant decline in immobility after treatment with 2.0 mg/kg tropisetron in both groups. In addition, a significant decline in swimming was observed in the estrous rats (proestrous-estrous group) after treatment with 2.0 mg/kg tropisetron. There were no significant effects of tropisetron on struggling in any groups examined.

  17. 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.

  18. 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.

  19. 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.

  20. Effect of L-arginine on metabolism of polyamines in rat's brain with extrahepatic cholestasis.

    Science.gov (United States)

    Sokolovic, Dusan; Bjelakovic, Gordana; Nikolic, Jelenka; Djindjic, Boris; Pavlovic, Dusica; Kocic, Gordana; Stojanovic, Ivana; Pavlovic, Voja

    2010-01-01

    Cholestatic encephalopathy results from accumulation of unconjugated bilirubin and hydrophobic bile acids in the brain. The aim of this study was to determine disturbances of polyamine metabolism in the brains of rats with experimental extrahepatic cholestasis and the effects of L-arginine administration. Wister rats were divided into groups: I: sham-operated, II: rats treated with L-arginine, III: animals with bile-duct ligation (BDL), and IV: cholestatic-BDL rats treated with L-arginine. Increased plasma gamma-glutamyltransferase and alkaline phosphatase activity and increased bile-acids and bilirubin levels in BDL rats were reduced by administration of L-arginine (P < 0.001). Cholestasis increased the brain's putrescine (P < 0.001) and decreased spermidine and spermine concentration (P < 0.05). The activity of polyamine oxidase was increased (P < 0.001) and diamine oxidase was decreased (P < 0.001) in the brains of BDL rats. Cholestasis increased the activity of arginase (P < 0.05) and decreased the level of citrulline (P < 0.001). Administration of L-arginine in BDL rats prevents metabolic disorders of polyamines and establishes a neuroprotective role in the brain during cholestasis.

  1. A longitudinal analysis of regional brain volumes in macaques exposed to X-irradiation in early gestation.

    Directory of Open Access Journals (Sweden)

    Kristina Aldridge

    Full Text Available BACKGROUND: Early gestation represents a period of vulnerability to environmental insult that has been associated with adult psychiatric disease. However, little is known about how prenatal perturbation translates into adult brain dysfunction. Here, we use a longitudinal study design to examine the effects of disruption of early gestational neurogenesis on brain volume in the non-human primate. METHODS AND PRINCIPAL FINDINGS: Five Rhesus macaques were exposed to x-irradiation in early gestation (E30-E41, and four control monkeys were sham-irradiated at comparable ages. Whole brain magnetic resonance imaging was performed at 6 months, 12 months, and 3 and 5 years of age. Volumes of whole cerebrum, cortical gray matter, caudate, putamen, and thalamus were estimated using semi-automated segmentation methods and high dimensional brain mapping. Volume reductions spanning all ages were observed in irradiated monkeys in the putamen (15-24%, p = 0.01 and in cortical gray matter (6-15%, p = 0.01. Upon covarying for whole cerebral volume, group differences were reduced to trend levels (putamen: p = 0.07; cortical gray matter: p = 0.08. No group-by-age effects were significant. CONCLUSIONS: Due to the small number of observations, the conclusions drawn from this study must be viewed as tentative. Early gestational irradiation may result in non-uniform reduction of gray matter, mainly affecting the putamen and cerebral cortex. This may be relevant to understanding how early prenatal environmental insult could lead to brain morphological differences in neurodevelopmental diseases.

  2. Population-averaged diffusion tensor imaging atlas of the Sprague Dawley rat brain.

    Science.gov (United States)

    Veraart, Jelle; Leergaard, Trygve B; Antonsen, Bjørnar T; Van Hecke, Wim; Blockx, Ines; Jeurissen, Ben; Jiang, Yi; Van der Linden, Annemie; Johnson, G Allan; Verhoye, Marleen; Sijbers, Jan

    2011-10-15

    Rats are widely used in experimental neurobiological research, and rat brain atlases are important resources for identifying brain regions in the context of experimental microsurgery, tissue sampling, and neuroimaging, as well as comparison of findings across experiments. Currently, most available rat brain atlases are constructed from histological material derived from single specimens, and provide two-dimensional or three-dimensional (3D) outlines of diverse brain regions and fiber tracts. Important limitations of such atlases are that they represent individual specimens, and that finer details of tissue architecture are lacking. Access to more detailed 3D brain atlases representative of a population of animals is needed. Diffusion tensor imaging (DTI) is a unique neuroimaging modality that provides sensitive information about orientation structure in tissues, and is widely applied in basic and clinical neuroscience investigations. To facilitate analysis and assignment of location in rat brain neuroimaging investigations, we have developed a population-averaged three-dimensional DTI atlas of the normal adult Sprague Dawley rat brain. The atlas is constructed from high resolution ex vivo DTI images, which were nonlinearly warped into a population-averaged in vivo brain template. The atlas currently comprises a selection of manually delineated brain regions, the caudate-putamen complex, globus pallidus, entopeduncular nucleus, substantia nigra, external capsule, corpus callosum, internal capsule, cerebral peduncle, fimbria of the hippocampus, fornix, anterior commisure, optic tract, and stria terminalis. The atlas is freely distributed and potentially useful for several purposes, including automated and manual delineation of rat brain structural and functional imaging data.

  3. [Immunological reactivity of rats exposed on the Kosmos-605 and 690 biosatellites].

    Science.gov (United States)

    Ivanov, A A; Shvets, V N

    1979-01-01

    Immunological reactivity of rats flown aboard the biosatellites Cosmos-605 and Cosmos-690 was compared with respect to the complementary activity of serum and frequency antibodies to sheep red blood cells. Cosmos-605 rats showed changes that rapidly returned to the normal whereas Cosmos-690 rats irradiated inflight with a dose of 800 rad exhibited significant and stable changes in immunological reactivity. Those latter seemed to be associated with the combined effect of ionizing radiation and other space flight factors.

  4. Effects of an acute and a sub-chronic 900 MHz GSM exposure on brain activity and behaviors of rats

    Energy Technology Data Exchange (ETDEWEB)

    Elsa Brillaud; Aleksandra Piotrowski; Anthony Lecomte; Franck Robidel; Rene de Seze [Toxicology Unit, INERIS, Verneuil en Halatte (France)

    2006-07-01

    Radio frequencies are suspected to produce health effects. Concerning the mobile phone technology, according to position during use (close to the head), possible effects of radio frequencies on the central nervous system have to be evaluated. Previous works showed contradictory results, possibly due to experimental design diversity. In the framework of R.A.M.P. 2001 project, we evaluated possible effect of a 900 MHz GSM exposure on the central nervous system of rat at a structural, a functional and a behavioral level after acute or sub-chronic exposures. Rats were exposed using a loop antenna system to different S.A.R. levels and durations, according to results of the French C.O.M.O.B.I.O. 2001 project. A functional effect was found (modification of the cerebral activity and increase of the glia surface) after an acute exposure, even at a low level of brain averaged S.A.R. (1.5 W/kg). No cumulative effect was observed after a sub-chronic exposure (same amplitude of the effect). No structural or behavioral consequence was noted. We do not conclude on the neurotoxicity of the 900 MHz GSM exposure on the rat brain. Our results do not indicate any health risk. (authors)

  5. Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

    Directory of Open Access Journals (Sweden)

    Chatterjee Ajay K

    2003-02-01

    Full Text Available Abstract Background Alteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. Results Protein restriction does not have any significant impact on regional aluminum and γ-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate α-decarboxylase and γ-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. Conclusion The alterations of regional brain glutamate and γ-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders.

  6. Immunocytochemical study on the intracellular localization of the type 2 glucocorticoid receptor in the rat brain

    NARCIS (Netherlands)

    Eekelen, J.A.M. van; Kiss, J.Z.; Westphal, H.M.; Kloet, E.R. de

    1987-01-01

    The localization of the glucocorticoid receptor (GR) (type 2) in the rat brain was studied with immunocytochemistry using a monoclonal antibody against the rat liver GR. Strong GR immunoreactivity (GR-ir) was observed in neurons of limbic and brainstem structures known to be associated with the stre

  7. Expression of annexin and Annexin-mRNA in rat brain under influence of steroid drugs

    NARCIS (Netherlands)

    Voermans, PH; Go, KG; ter Horst, GJ; Ruiters, MHJ; Solito, E; Parente, L; James, HE; Marshall, LF; Reulen, HJ; Baethmann, A; Marmarou, A; Ito, U; Hoff, JT; Kuroiwa, T; Czernicki, Z

    1997-01-01

    Brain tissue of rats pretreated with methylprednisolone or with the 21-aminosteroid U74389F, and that of untreated control rats, was assessed for the expression of Annexin-l (Anx-1) and the transcription of its mRNA. For this purpose Anx-1 cDNA was amplified and simultaneously a T7-RNA-polymerase pr

  8. 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

  9. 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 acti