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Sample records for adult rats neuroprotection

  1. Neuroprotective effects of N-acetyl-cysteine and acetyl-L-carnitine after spinal cord injury in adult rats.

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    Amar Karalija

    Full Text Available Following the initial acute stage of spinal cord injury, a cascade of cellular and inflammatory responses will lead to progressive secondary damage of the nerve tissue surrounding the primary injury site. The degeneration is manifested by loss of neurons and glial cells, demyelination and cyst formation. Injury to the mammalian spinal cord results in nearly complete failure of the severed axons to regenerate. We have previously demonstrated that the antioxidants N-acetyl-cysteine (NAC and acetyl-L-carnitine (ALC can attenuate retrograde neuronal degeneration after peripheral nerve and ventral root injury. The present study evaluates the effects of NAC and ALC on neuronal survival, axonal sprouting and glial cell reactions after spinal cord injury in adult rats. Tibial motoneurons in the spinal cord were pre-labeled with fluorescent tracer Fast Blue one week before lumbar L5 hemisection. Continuous intrathecal infusion of NAC (2.4 mg/day or ALC (0.9 mg/day was initiated immediately after spinal injury using Alzet 2002 osmotic minipumps. Neuroprotective effects of treatment were assessed by counting surviving motoneurons and by using quantitative immunohistochemistry and Western blotting for neuronal and glial cell markers 4 weeks after hemisection. Spinal cord injury induced significant loss of tibial motoneurons in L4-L6 segments. Neuronal degeneration was associated with decreased immunostaining for microtubular-associated protein-2 (MAP2 in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker GFAP and microglial marker OX42 was increased. Treatment with NAC and ALC rescued approximately half of the motoneurons destined to die. In addition, antioxidants restored MAP2 and synaptophysin immunoreactivity. However, the perineuronal synaptophysin labeling was not recovered. Although both treatments promoted axonal sprouting, there was no effect on reactive astrocytes

  2. Organotypic explant culture of adult rat retina for in vitro investigations of neurodegeneration, neuroprotection and cell transplantation

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    sprotocols

    2015-01-01

    This protocol details a method for isolating retinal tissue from adult rats as an organotypic culture to study neurobiological processes in mature tissue. It combines the efficiency and control common to in vitro techniques with close imitation of the in vivo environment. Eyes from adult rats are enucleated and the neural retina is isolated. Tissue is cut into quarters, yielding eight retinal explants per animal, and cultured at a fluid/air interface on organotypic culture membranes. Explanta...

  3. Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

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    Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

    2017-02-01

    There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

  4. Paraquat induces oxidative stress, neuronal loss in substantia nigra region and Parkinsonism in adult rats: Neuroprotection and amelioration of symptoms by water-soluble formulation of Coenzyme Q10

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    Sridhar TS

    2009-07-01

    Full Text Available Abstract Background Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance. Results Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats. Conclusion Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of Parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

  5. The neuroprotection of Aspirin on Cerebral Ischemia-Reperfusion rats

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    QiuLi-ying; YuJuan; ChenChong-hong; ZhouYu

    2004-01-01

    AIM: Aspirin (aeetylsalicylic acid, ASA as a nonsteroidal anti-inflammatory drug not only has well-established efficacy in anti-thromboxane, but also has direct neuroprotective effect. In this study, we design to investigate its neuroprotective effect on focal cerebral ischemia-reperfusion injury (CIRI rats, and its effect on ATP level from occluded brain tis-

  6. Transplants of adult mesenchymal and neural stem cells provide neuroprotection and behavioral sparing in a transgenic rat model of Huntington's disease.

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    Rossignol, Julien; Fink, Kyle; Davis, Kendra; Clerc, Steven; Crane, Andrew; Matchynski, Jessica; Lowrance, Steven; Bombard, Matthew; Dekorver, Nicholas; Lescaudron, Laurent; Dunbar, Gary L

    2014-02-01

    Stem cells have gained significant interest as a potential treatment of neurodegenerative diseases, including Huntington's disease (HD). One source of these cells is adult neural stem cells (aNSCs), which differentiate easily into neuronal lineages. However, these cells are vulnerable to immune responses following transplantation. Another source is bone-marrow-derived mesenchymal stem cells (MSCs), which release neurotrophic factors and anti-inflammatory cytokines following transplantation, and are less vulnerable to rejection. The goal of this study was to compare the efficacy of transplants of MSCs, aNSCs, or cotransplants of MSCs and aNSCs for reducing deficits in a transgenic rat model of HD. HD rats received intrastriatal transplantations of 400,000 MSCs, aNSCs, or a combination of MSCs/aNSCs, while wild-type and HD controls were given vehicle. Rats were tested on the rotarod over the course of 20 weeks. The results indicated that transplants of: (a) aNSCs produced a strong immune response and conferred short-term behavioral benefits; (b) MSCs elicited a relatively weak immune response, and provided a longer term behavioral benefit; and (c) combined MSCs and aNSCs conferred long-term behavioral benefits and increased survival of the transplanted aNSCs. The finding that cotransplanting MSCs with aNSCs can prolong aNSC survival and provide greater behavioral sparing than when the transplants contains only aNSCs suggests that MSCs are capable of creating a more suitable microenvironment for aNSC survival. This cotransplantation strategy may be useful as a future therapeutic option for treating HD, especially if long-term survival of differentiated cells proves to be critically important for preserving lasting functional outcomes.

  7. Neuroprotective Effects of Liraglutide for Stroke Model of Rats

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    Kenichiro Sato

    2013-10-01

    Full Text Available The number of diabetes mellitus (DM patients is increasing, and stroke is deeply associated with DM. Recently, neuroprotective effects of glucagon-like peptide-1 (GLP-1 are reported. In this study, we explored whether liraglutide, a GLP-1 analogue exerts therapeutic effects on a rat stroke model. Wistar rats received occlusion of the middle cerebral artery for 90 min. At one hour after reperfusion, liraglutide or saline was administered intraperitoneally. Modified Bederson’s test was performed at 1 and 24 h and, subsequently, rats were euthanized for histological investigation. Peripheral blood was obtained for measurement of blood glucose level and evaluation of oxidative stress. Brain tissues were collected to evaluate the level of vascular endothelial growth factor (VEGF. The behavioral scores of liraglutide-treated rats were significantly better than those of control rats. Infarct volumes of liraglutide-treated rats at were reduced, compared with those of control rats. The level of derivatives of reactive oxygen metabolite was lower in liraglutide-treated rats. VEGF level of liraglutide-treated rats in the cortex, but not in the striatum significantly increased, compared to that of control rats. In conclusion, this is the first study to demonstrate neuroprotective effects of liraglutide on cerebral ischemia through anti-oxidative effects and VEGF upregulation.

  8. Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease

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    M.M. Ferro

    2007-01-01

    Full Text Available There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg and xylazine (3 mg/kg (K/X on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP or 6-hydroxydopamine (6-OHDA rat models of Parkinson's disease. The bilateral infusion of MPTP (100 µg/side or 6-OHDA (10 µg/side into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67% or severe (~91% loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33% of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51% due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.

  9. Endogenous BDNF protein is increased in adult rat hippocampus after a kainic acid induced excitotoxic insult but exogenous BDNF is not neuroprotective.

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    Rudge, J S; Mather, P E; Pasnikowski, E M; Cai, N; Corcoran, T; Acheson, A; Anderson, K; Lindsay, R M; Wiegand, S J

    1998-02-01

    Systemic administration of the excitotoxin kainic acid to adult rats results in a well defined pattern of loss of the CA1 and CA3 pyramidal neurons of the hippocampus. Prior to this neuronal loss, brain-derived neurotrophic factor (BDNF) mRNA is substantially increased. We show here that BDNF protein is increased after excitotoxic insult in specific areas of the hippocampus, reaching maximal levels 24 h after the insult. BDNF protein levels in the hippocampus increase in direct relation to the severity of seizure. Up to 7 days after injection of kainic acid, levels of full-length TrkB protein were unchanged, whereas levels of truncated TrkB protein were significantly increased by 12 h. To determine whether elevations in BDNF protein levels are potentially beneficial to hippocampal neurons exposed to an excitotoxic stress, we infused exogenous BDNF prior to and during the period of neuronal death caused by kainic acid. We find that administration of high levels of exogenous BDNF does not affect severity of seizure, but does in fact, exacerbate the injury caused by kainic acid, specifically to CA3 pyramidal neurons. Although there was a trend toward sparing of CA1 pyramidal neurons on the side infused with BDNF, this was not significant. In the same paradigm, infusion of exogenous NT-3 had no effect.

  10. Free-Radical Scavenger Edaravone Treatment Confers Neuroprotection Against Traumatic Brain Injury in Rats

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    Wang, Guo-Hua; Li, Yong-Cai; Li, Xia; Shi, Hong; Gao, Yan-Qin; Vosler, Peter S.

    2011-01-01

    Abstract Traumatic brain injury (TBI) is one of the leading causes of neurological disability in young adults. Edaravone, a novel synthetic small-molecule free-radical scavenger, has been shown to have a neuroprotective effect in both animal models of cerebral ischemia and stroke patients; however, the underlying mechanism is poorly understood. In this report, we investigated the potential mechanisms of edaravone treatment in a rat model of TBI. TBI was induced in the right cerebral cortex of male adult rats using Feeney's weight-drop method. Edaravone (0.75, 1.5, or 3 mg/kg) or vehicle (normal saline) was intravenously administered at 2 and 12 h after TBI. Edaravone treatment significantly decreased hippocampal CA3 neuron loss, reduced oxidative stress, and decreased neuronal programmed cell death compared to vehicle treatment. The protective effects of edaravone treatment were also related to the pathology of TBI on non-neuronal cells, as edaravone decreased astrocyte and glial activation. Lastly, edaravone treatment significantly reduced the presence of inflammatory cytokines, cerebral edema, blood–brain barrier (BBB) permeability, and, importantly, neurological deficits following TBI. Our results suggest that edaravone exerts a neuroprotective effect in the rat model of TBI. The likely mechanism is via inhibiting oxidative stress, leading to a decreased inflammatory response and glial activation, and thereby reducing neuronal death and improving neurological function. PMID:21732763

  11. Neuroprotective effects of octreotide on diabetic neuropathy in rats.

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    Solmaz, Volkan; Çınar, Bilge Piri; Yiğittürk, Gürkan; Özlece, Hatice Köse; Avni Eroglu, Hüseyin; Tekatas, Aslan; Erbaş, Oytun; Taşkıran, Dilek

    2017-02-26

    The purpose of the present study is to investigate the possible healing effects of octreotide (OCT) on motor performance, electrophysiological and histopathological findings of diabetic neuropathy in a rat model of diabetes mellitus (DM). To induce diabetes, rats were administered a single dose (60mg/kg) of streptozotocin (STZ). Diabetic rats were treated either with saline (1ml/kg/day, n=7) or OCT (0.1mg/kg/day, n=7) for four weeks. Seven rats served as control group and received no treatment. At the end of the study, electromyography (EMG), gross motor function (inclined plate test), general histology and the perineural thickness of sciatic nerve were evaluated. At the end of study, weight loss was significantly lower in OCT treated rats than that of saline treated ones (pdiabetic rats with OCT significantly counteracted these alterations in EMG. Furthermore, OCT significantly improved the motor performance scores in diabetic rats (pdiabetic neuropathy, which promisingly support the use of OCT as a neuroprotective agent in patients with diabetic neuropathy.

  12. Neuroprotective effect of ebselen against intracerebroventricular streptozotocin-induced neuronal apoptosis and oxidative stress in rats.

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    Unsal, Cuneyt; Oran, Mustafa; Albayrak, Yakup; Aktas, Cevat; Erboga, Mustafa; Topcu, Birol; Uygur, Ramazan; Tulubas, Feti; Yanartas, Omer; Ates, Ozkan; Ozen, Oguz Aslan

    2016-04-01

    The goal of this study was to examine the neuroprotective effect of ebselen against intracerebroventricular streptozotocin (ICV-STZ)-induced oxidative stress and neuronal apoptosis in rat brain. A total of 30 adult male Sprague-Dawley rats were randomly divided into 3 groups of 10 animals each: control, ICV-STZ, and ICV-STZ treated with ebselen. The ICV-STZ group rats were injected bilaterally with ICV-STZ (3 mg/kg) on days 1 and 3, and ebselen (10 mg/kg/day) was administered for 14 days starting from 1st day of ICV-STZ injection to day 14. Rats were killed at the end of the study and brain tissues were removed for biochemical and histopathological investigation. Our results demonstrated, for the first time, the neuroprotective effect of ebselen on Alzheimer's disease (AD) model in rats. Our present study, in ICV-STZ group, showed significant increase in tissue malondialdehyde levels and significant decrease in enzymatic antioxidants superoxide dismutase and glutathione peroxidase in the frontal cortex tissue. The histopathological studies in the brain of rats also supported that ebselen markedly reduced the ICV-STZ-induced histopathological changes and well preserved the normal histological architecture of the frontal cortex tissue. The number of apoptotic neurons was increased in frontal cortex tissue after ICV-STZ administration. Treatment of ebselen markedly reduced the number of degenerating apoptotic neurons. The study demonstrates the effectiveness of ebselen, as a powerful antioxidant, in preventing the oxidative damage and morphological changes caused by ICV-STZ in rats. Thus, ebselen may have a therapeutic value for the treatment of AD.

  13. Antivasoconstrictor effect of the neuroprotective agent dexrazoxane in rat aorta.

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    Vidrio, Horacio; Carrasco, Omar F; Rodríguez, Rodolfo

    2006-12-14

    Dexrazoxane is used clinically to reduce the cardiotoxicity of anthracycline cancer chemotherapeutic agents, acting by an iron-chelating antioxidant mechanism. In a study designed to explore the possible mechanism of the recently described neuroprotective effect of the drug in cerebral ischemia, its influence on vascular reactivity was determined in rat aortic rings. Dexrazoxane was found to be devoid of direct contractile or relaxant activity and to have no influence on responses to acetylcholine or histamine (relaxation), or to angiotensin or serotonin (contraction). In contrast, it decreased contractions to norepinephrine, as evidenced by rightward displacement of the concentration-response curves. The effect was prevented by the removal of the endothelium and by the alpha(2)-adrenoceptor antagonist yohimbine; it was partially antagonized by the endothelium-derived depolarizing factor inhibitor clotrimazole, but was not affected by L-NAME or indomethacin, inhibitors of endothelial nitric oxide and prostacyclin production. The anti-contractile effect did not occur in rings stimulated with the alpha(1)-adrenoceptor agonist phenylephrine. It was concluded that dexrazoxane opposes norepinephrine vascular contraction by enhancing endothelial alpha(2)-adrenoceptor-mediated release of relaxing factor(s). The drug could thus offset the deleterious vasoconstriction elicited by the increased circulating catecholamines present during cerebral ischemia, and by this mechanism produce neuroprotection.

  14. Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury

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    Li, Yonggang [Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA, 30310 (United States); Lein, Pamela J. [Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, 95616 (United States); Liu, Cuimei [Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA, 30310 (United States); Bruun, Donald A.; Giulivi, Cecilia [Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, 95616 (United States); Ford, Gregory D. [Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA, 30310 (United States); Department of Biology, Morehouse College, Atlanta, GA, 30310 (United States); Tewolde, Teclemichael [Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA, 30310 (United States); Ross-Inta, Catherine [Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, 95616 (United States); Ford, Byron D., E-mail: bford@msm.edu [Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA, 30310 (United States)

    2012-07-15

    Current medical countermeasures against organophosphate (OP) nerve agents are effective in reducing mortality, but do not sufficiently protect the CNS from delayed brain damage and persistent neurological symptoms. In this study, we examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed neuronal cell death following acute intoxication with the OP diisopropylflurophosphate (DFP). Adult male Sprague–Dawley rats were pretreated with pyridostigmine (0.1 mg/kg BW, i.m.) and atropine methylnitrate (20 mg/kg BW, i.m.) prior to DFP (9 mg/kg BW, i.p.) intoxication to increase survival and reduce peripheral signs of cholinergic toxicity but not prevent DFP-induced seizures or delayed neuronal injury. Pretreatment with NRG-1 did not protect against seizures in rats exposed to DFP. However, neuronal injury was significantly reduced in most brain regions by pretreatment with NRG-1 isoforms NRG-EGF (3.2 μg/kg BW, i.a) or NRG-GGF2 (48 μg/kg BW, i.a.) as determined by FluroJade-B labeling in multiple brain regions at 24 h post-DFP injection. NRG-1 also blocked apoptosis and oxidative stress-mediated protein damage in the brains of DFP-intoxicated rats. Administration of NRG-1 at 1 h after DFP injection similarly provided significant neuroprotection against delayed neuronal injury. These findings identify NRG-1 as a promising adjuvant therapy to current medical countermeasures for enhancing neuroprotection against acute OP intoxication. -- Highlights: ► NRG-1 blocked DFP induced neuronal injury. ► NRG-1 did not protect against seizures in rats exposed to DFP. ► NRG-1 blocked apoptosis and oxidative stress in the brains of DFP-intoxicated rats. ► Administration of NRG-1 at 1 h after DFP injection prevented delayed neuronal injury.

  15. Selective androgen receptor modulator RAD140 is neuroprotective in cultured neurons and kainate-lesioned male rats.

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    Jayaraman, Anusha; Christensen, Amy; Moser, V Alexandra; Vest, Rebekah S; Miller, Chris P; Hattersley, Gary; Pike, Christian J

    2014-04-01

    The decline in testosterone levels in men during normal aging increases risks of dysfunction and disease in androgen-responsive tissues, including brain. The use of testosterone therapy has the potential to increase the risks for developing prostate cancer and or accelerating its progression. To overcome this limitation, novel compounds termed "selective androgen receptor modulators" (SARMs) have been developed that lack significant androgen action in prostate but exert agonist effects in select androgen-responsive tissues. The efficacy of SARMs in brain is largely unknown. In this study, we investigate the SARM RAD140 in cultured rat neurons and male rat brain for its ability to provide neuroprotection, an important neural action of endogenous androgens that is relevant to neural health and resilience to neurodegenerative diseases. In cultured hippocampal neurons, RAD140 was as effective as testosterone in reducing cell death induced by apoptotic insults. Mechanistically, RAD140 neuroprotection was dependent upon MAPK signaling, as evidenced by elevation of ERK phosphorylation and inhibition of protection by the MAPK kinase inhibitor U0126. Importantly, RAD140 was also neuroprotective in vivo using the rat kainate lesion model. In experiments with gonadectomized, adult male rats, RAD140 was shown to exhibit peripheral tissue-specific androgen action that largely spared prostate, neural efficacy as demonstrated by activation of androgenic gene regulation effects, and neuroprotection of hippocampal neurons against cell death caused by systemic administration of the excitotoxin kainate. These novel findings demonstrate initial preclinical efficacy of a SARM in neuroprotective actions relevant to Alzheimer's disease and related neurodegenerative diseases.

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

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    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.

  17. Tenoxicam exerts a neuroprotective action after cerebral ischemia in rats.

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    Galvão, Rita I M; Diógenes, João P L; Maia, Graziela C L; Filho, Emídio A S; Vasconcelos, Silvânia M M; de Menezes, Dalgimar B; Cunha, Geanne M A; Viana, Glauce S B

    2005-01-01

    In this study we investigated the effects of Tenoxicam, a type 2 cyclooxygenase (COX-2) inhibitor, on brain damage induced by ischemia-reperfusion. Male Wistar rats (18-month old average) were anesthetized and submitted to ischemia occlusion of both common carotid arteries (BCAO) for 45 min. After 24 h of reperfusion, rats were decapitated and hippocampi removed for further assays. Animals were divided into sham-operated, ischemia, ischemia + Tenoxicam 2.5 mg/kg, and ischemia + Tenoxicam 10 mg/kg groups. Tenoxicam was administered intraperitoneally immediately after BCAO. Histological analyses show that ischemia produced significant striatal as well as hippocampal lesions which were reversed by the Tenoxicam treatment. Tenoxicam also significantly reduced, to control levels, the increased myeloperoxidase activity in hippocampus homogenates observed after ischemia. However, nitrite concentrations showed only a tendency to decrease in the ischemia + Tenoxicam groups, as compared to that of ischemia alone. On the other hand, hippocampal glutamate and aspartate levels were not altered by Tenoxicam. In conclusion, we showed that ischemia is certainly related to inflammation and to increased free radical production, and selective COX-2 inhibitors might be neuroprotective agents of potential benefit in the treatment of cerebral brain ischemia.

  18. Neuroprotective Effect of Melatonin on Retinal Ganglion Cells in Rats

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    TANG Qiongyan; HU Yizhen; CAO Yang

    2006-01-01

    To investigate the neuroprotective effect of melatonin (MT) on retinal ganglion cells (RGCs) in rats with ischemia reperfusion injury (RIR), 24 healthy SD rats were randomly divided into two groups:group A and group B. RIR model was induced in the left eyes by increasing the pressure of the anterior chamber. Group A was treated with 10 % alcohol- normal saline (1 mL/kg/d, ip), while group B was treated with 0.5 % MT (1 mL/kg/d, ip). On the basis of the time interval between the left eyes RIR and the sacrifice, rats in both group A and group B were further divided into 3 subgroups: groups A1 and B1 (days 7), groups A2 and B2 (days 14), groups A3 and B3 (days 30), with4 rats in each subgroup. 7 day before the sacrifice, 3 % fluorogold was bilaterally injected into superior colliculi and geniculate body. The eyes were enucleated after being sacrificed, and mounting of the retina from both eyes was performed on a slide and observed under a fluorescence microscope. Four photos were taken from each of the four quadrants of the retina.The labeled-RGCs were counted by using a computerized image analyzer. The rate of the labeledRGCs was used for statistical analysis. Our results showed that, in group A, the rate of the labeled-RGCs was (77. 16±6.35) %, (65.53±7.01) %, (53.85±4.38) % on day 7, 14 and 30.In group B, the rate of the labeled-RGCs was (81.33±9.27) %, (79.80±8.36) %, (80.34±11.05) % on day 7, 14 and 30. In group B, which was treated with MT after RIR, the rate of labeled-RGCs was significantly higher than that of group A on day 14 and day 30 (P<0.05). It is concluded that, in the RIR rats, MT therapy could increase the survival rate of the RGCs and could rescue and restore the injured RGCs.

  19. Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model.

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    Wenru Su

    Full Text Available Glaucoma is a leading cause of irreversible blindness. Injury of retinal ganglion cells (RGCs accounts for visual impairment of glaucoma. Here, we report rapamycin protects RGCs from death in experimental glaucoma model and the underlying mechanisms. Our results showed that treatment with rapamycin dramatically promote RGCs survival in a rat chronic ocular hypertension model. This protective action appears to be attributable to inhibition of neurotoxic mediators release and/or direct suppression of RGC apoptosis. In support of this mechanism, in vitro, rapamycin significantly inhibits the production of NO, TNF-α in BV2 microglials by modulating NF-κB signaling. In experimental animals, treatment with rapamycin also dramatically inhibited the activation of microglials. In primary RGCs, rapamycin was capable of direct suppression the apoptosis of primary RGCs induced by glutamate. Mechanistically, rapamycin-mediated suppression of RGCs apoptosis is by sparing phosphorylation of Akt at a site critical for maintenance of its survival-promoting activity in cell and animal model. These results demonstrate that rapamycin is neuroprotective in experimental glaucoma, possibly via decreasing neurotoxic releasing and suppressing directly apoptosis of RGCs.

  20. Neuroprotective effect of melatonin in experimental optic neuritis in rats.

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    Aranda, Marcos L; González Fleitas, María F; De Laurentiis, Andrea; Keller Sarmiento, María I; Chianelli, Mónica; Sande, Pablo H; Dorfman, Damián; Rosenstein, Ruth E

    2016-04-01

    Optic neuritis (ON) is an inflammatory, demyelinating, and neurodegenerative condition of the optic nerve, which might induce permanent vision loss. Currently, there are no effective therapies for this disorder. We have developed an experimental model of primary ON in rats through a single microinjection of 4.5 μg of bacterial lipopolysaccharide (LPS) into the optic nerve. Since melatonin acts as a pleiotropic therapeutic agent in various neurodegenerative diseases, we analyzed the effect of melatonin on LPS-induced ON. For this purpose, LPS or vehicle were injected into the optic nerve from adult male Wistar rats. One group of animals received a subcutaneous pellet of 20 mg melatonin at 24 hr before vehicle or LPS injection, and another group was submitted to a sham procedure. Melatonin completely prevented the decrease in visual evoked potentials (VEPs), and pupil light reflex (PLR), and preserved anterograde transport of cholera toxin β-subunit from the retina to the superior colliculus. Moreover, melatonin prevented microglial reactivity (ED1-immunoreactivity, P Melatonin completely prevented the increase in nitric oxide synthase 2, cyclooxygenase-2 levels (Western blot) and TNFα levels, and partly prevented lipid peroxidation induced by experimental ON. When the pellet of melatonin was implanted at 4 days postinjection of LPS, it completely reversed the decrease in VEPs and PLR. These data suggest that melatonin could be a promising candidate for ON treatment.

  1. Neuroprotective effects of the immunomodulatory drug Setarud on cerebral ischemia in male rats

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    Farzaneh Vafaee; Nasser Zangiabadi; Fatemeh Mehdi Pour; Farzaneh Dehghanian; Majid Asadi-Shekaari; Hossein Karimi Afshar

    2012-01-01

    Anti-inflammatory and anti-oxidant agents can alleviate ischemic cerebral injury. The immunomodulary drug Setarud, which is composed of herbal extracts including Rosa canina, Urtica dioica and Tanacetum vulgare, supplemented with selenium exhibits anti-inflammatory and anti-oxidant properties. Therefore, we hypothesized that Setarud will have a neuroprotective effect against ischemic cerebral injury. To validate this hypothesis, rats were intraperitoneally administered with 0.66 mL/kg Setarud for 30 minutes after middle cerebral artery occlusion. Triphenyltetrazolium chloride staining showed that Setarud could reduce cerebral infarct volume of rats subjected to cerebral ischemia. Transmission electron microscopy and hematoxylin-eosin staining results showed that Setarud could alleviate the degenerative changes in cortical neurons of rats with cerebral ischemia. The inclined plate test and prehensile test showed that Setarud could significantly improve the motor function of rats with cerebral ischemia. These findings suggest that Setarud shows neuroprotective effects against ischemic brain injury.

  2. Neuroprotective effect of AG490 in experimental traumatic brain injury of rats

    Institute of Scientific and Technical Information of China (English)

    DU Ai-ling; JI Tai-ling; YANG Bin; CAO Jian-feng; ZHANG Xing-guang; LI Yu; PAN Shun

    2013-01-01

    Background Traumatic brain injury (TBI) is a major cause of death and disability in children and young adults worldwide.Therefore,we investigated the role of AG490 in regulating brain oedema,expression of CD40 and neurological function after TBI.Methods Sprague Dawley rats (n=240) were randomly divided into a sham operation group,TBl+saline group and TBI+AG490 (JAK/STAT inhibitor) group.Members of each group were euthanized at 6,12,24 or 72 hours after injury.Neurological severity score (NSS) was used to evaluate the severity of neurological damage.Brain water was quantitated by wet/dry weight method.The expression of CD40 was assessed by flow cytometry.Results In both the TBl+saline group and the TBI+AG490 group,the brain water content was elevated after TBI,reached a peak at 24-hour and remained high for the rest of the period investigated; the expression of CD40 reached a peak 24hours after TBI; the NSS was elevated after TBI and then decreased after 6 hours.Elevations in the level of CD40,degree of brain edema and NSS after TBI were significantly reduced in TBI+AG490 group.Conclusion Inhibition of the JAK/STAT signalling pathway reduces brain oedema,decreases the expression of CD40 and exerts neuroprotective effects after TBI.

  3. Neuroprotective role of heat shock protein 70 in the rostral ventrolateral medulla during acute mevinphos intoxication in the rat.

    Science.gov (United States)

    Chang, Chi; Chang, Alice Y W; Chan, Samuel H H

    2004-01-01

    Heat shock protein (HSP) is a family of highly conserved proteins that respond to stress and participate actively in cytoprotection. Within the HSP family, HSP70 is the major inducible member that confers protection against cell death. This study investigated whether HSP70 plays a neuroprotective role at the rostral ventrolateral medulla (RVLM), the origin of sympathetic neurogenic vasomotor tone in the medulla oblongata where the organophosphate insecticide mevinphos (Mev) acts to elicit cardiovascular toxicity. Experiments were carried out in adult male Sprague-Dawley rats that were maintained under propofol anesthesia. Intravenous administration of Mev (960 microg/kg) induced a significant increase in the HSP70 level in the ventrolateral medulla during phase I ('pro-life' phase), and returned to baseline during phase II ('pro-death' phase) Mev intoxication. Compared to artificial cerebrospinal fluid, normal mouse serum (1:20), or sense hsp70 oligonucleotide (50 pmol) pretreatment, microinjection of an anti-HSP70 antiserum (1:20) or an antisense hsp70 oligonucleotide (50 pmol) bilaterally into the RVLM significantly increased mortality, shortened the duration of phase I intoxication and augmented the induced hypotension in rats that received Mev (960 microg/ kg, i.v.). These results suggest that HSP70 induced in the RVLM during Mev intoxication provides neuroprotection against the organophosphate poison via prevention of cardiovascular depression.

  4. Neuroprotective effect of tyrosol on transient focal cerebral ischemia in rats.

    Science.gov (United States)

    Bu, Youngmin; Rho, Seongjoo; Kim, Jinmo; Kim, Mi Yeon; Lee, Dae Hee; Kim, Sun Yeou; Choi, Hoyoung; Kim, Hocheol

    2007-03-13

    Tyrosol (2-(4-hydroxyphenyl)ethanol) is a well-known phenolic compound with antioxidant properties that is present in wine, olive oil, and other plant-derived products. The purpose of this study was to determine the neuroprotective effect of tyrosol in a stroke animal model. By using the transient middle cerebral artery occlusion rat model (2 h of occlusion, 22 h of reperfusion), we investigated the effects of tyrosol on infarct volume and sensory motor function deficit by performing 2,3,5-triphenyltetrazolium chloride staining and behavior tests after ischemia. Tyrosol showed a dose-dependent neuroprotective effect that peaked at 64.9% in rats treated with 30 mg/kg of tyrosol. In rotarod, beam balance, and foot fault tests, tyrosol exhibited protective effects against the sensory motor dysfunction. In conclusion, our results suggest that tyrosol is an appropriate candidate to be used in stroke therapy.

  5. Neuroprotective effect of exogenous vascular endothelial growth factor on rat spinal cord neurons in vitro hypoxia

    Institute of Scientific and Technical Information of China (English)

    DING Xin-min; MAO Bo-yong; JIANG Shu; LI Sheng-fu; DENG Yi-ling

    2005-01-01

    Background Vascular endothelial growth factor (VEGF) is well known as a hypoxia-induced protein. That it markedly increased expression of VEGF and improvement of rat motor function after spinal cord injury suggested that VEGF could play a neuroprotective role in ischaemic tolerance. This study investigated whether vascular endothelial growth factor has direct neuroprotective effects on rat spinal cord neurons. Methods We employed primary cultures of embryonic rat spinal cord neurons, then administrated different concentrations of VEGF164 in the culture medium before hypoxia when the number of neurons was counted and the cell viability was detected by MTT. The neuronal apoptosis and expression of VEGF and its receptor genes were evaluated by terminal deoxynucleotidyl transferase mediated dUTP nick-end labelling (TUNEL) and immunohistochemistry. The VEGFR2/FLK-1 inhibitor, SU1498, was used to confirm whether the neuroprotective effect of VEGF was mediated through VEGFR2/Flk-1 receptors. Result In hypoxic conditions,the number and viability of neurons decreased progressively, while the number of TUNEL-positive cells increased along with the prolongation of hypoxic exposure. When the concentration of VEGF in cell culture medium reached 25 ng/ml, the cell viability increased 11% and neuronal apoptosis reduced to half, this effect was dose dependent and led to an approximately 25% increase in cell viability and about threefold decrease in TUNEL-positive cells at a maximally effective concentration of 100 ng/ml. In normal conditions, VEGF/Flk-1 but not VEGF/Flt-1 gene expressed at a low level: after hypoxia, the expression of VEGF/Flk-1, but not VEGF/Flt-1 was significantly increased. The protective effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor, SU1498. Conclusions VEGF has direct neuroprotective effects on rat spinal cord neurons, which may be mediated in vitro through VEGFR2/Flk-1 receptors.

  6. Retinal ganglion cell neuroprotection in a rat model of glaucoma following brimonidine, latanoprost or combined treatments.

    Science.gov (United States)

    Hernández, María; Urcola, J Haritz; Vecino, Elena

    2008-05-01

    The aim of the present study is to evaluate the neuroprotective effect of two antiglaucomatous substances, regardless of their hypotensive effect in the eye. Brimonidine, which does not reduce IOP when administered intraperitoneally, and latanoprost, which has a renowned hypotensive effect topically. We examined rat retinal ganglion cell (RGC) survival and size distribution in experimental glaucoma in response to different glaucomatous agents. IOP was elevated by episcleral vein cauterization (EVC) prior to the application of different treatments: (I) PBS application (control group), (II) intraperitoneal administration of brimonidine (a general hypotensive agent), (III) topical application of latanoprost (an ocular hypotensive agent), and (IV) latanoprost combined with brimonidine. After 12 weeks, RGCs were retrogradely labeled with fluorogold and RGC density was analyzed. EVC caused a significant increase (42%) in IOP in each group before drug treatment. After 12weeks of EVC, RGC survival in control vs. EVC rats was 78.9+/-3.2%. No IOP reduction was observed in brimonidine injected rats, but RGC survival at 12 weeks was total (103.7+/-2.7%). In latanoprost treated rats, IOP dropped by around 22% and 94.7+/-3.7% of the RGC population survived. Finally in the latanoprost+brimonidine combined group, IOP was significantly reduced by 25% and 94.4+/-2.2% of RGCs survived. Surprisingly, whereas EVC led to a 6% increase in RGC soma size, brimonidine treatment was associated with a 9% reduction in the soma size of RGCs at 12 weeks. We conclude that brimonidine exerts a neuroprotective effect via a mechanism which is independent of IOP reduction. These findings indicate that cell survival in glaucoma may be enhanced by neuroprotective strategies which are independent of IOP reduction. No synergistic neuroprotective effect was observed when both treatments were applied simultaneously.

  7. Comparative neuroprotective profile of statins in quinolinic acid induced neurotoxicity in rats.

    Science.gov (United States)

    Kalonia, Harikesh; Kumar, Puneet; Kumar, Anil

    2011-01-01

    A possible neuroprotective role has been recently suggested for 3H3MGCoA reductase inhibitors (statins). Here, we sought to determine neuroprotective effect of statins in quinolinic acid induced neurotoxicity in rats. Rats were surgically administered quinolinic acid and treated with Atorvastatin (10, 20 mg/kg), simvastatin (15, 30 mg/kg) and fluvastatin (5, 10 mg/kg) once daily up to 3 weeks. Atorvastatin (10, 20 mg/kg), simvastatin (30 mg/kg) and fluvastatin (10 mg/kg) treatment significantly attenuated the quinolinic acid induced behavioral (locomotor activity, rotarod performance and beam walk test), biochemical (lipid peroxidation, nitrite concentration, SOD and catalase), mitochondrial enzyme complex alterations in rats suggesting their free radical scavenging potential. Additionally, atorvastatin (10, 20 mg/kg), simvastatin (30 mg/kg) and fluvastatin (10 mg/kg) significantly decrease the TNF-α level and striatal lesion volume in quinolinic acid treated animals indicating their anti-inflammatory effects. In comparing the protective effect of different statins, atorvastatin is effective at both the doses while simvastatin and fluvastatins at respective lower doses were not able to produce the protective effect in quinolinic acid treated animals. These modulations can account, at least partly, for the beneficial effect of statins in our rodent model of striatal degeneration. Our findings show that statins could be explored as possible neuroprotective agents for neurodegenerative disorders such as HD.

  8. Neuroprotective effect of ginger on anti-oxidant enzymes in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Shanmugam, Kondeti Ramudu; Mallikarjuna, Korivi; Kesireddy, Nishanth; Sathyavelu Reddy, Kesireddy

    2011-04-01

    The aim of the present study was to investigate the effect of ginger on oxidative stress markers in the mitochondrial fractions of cerebral cortex (CC), cerebellum (CB), hippocampus (HC) and hypothalamus (HT) of diabetic rats. Diabetes exacerbates neuronal injury induced by hyperglycemia mediated oxidative damage. A marked decrease in anti-oxidant marker enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH) and increase in malondialdehyde (MDA) was observed in the diabetic rats. Decreased activities of anti-oxidant enzymes in diabetic rats were augmented on oral administration of ginger. Moreover, ginger administration depleted the MDA level, which was earlier increased in the diabetic rats. These results suggest that ginger exhibit a neuroprotective effect by accelerating brain anti-oxidant defense mechanisms and down regulating the MDA levels to the normal levels in the diabetic rats. Thus, ginger may be used as therapeutic agent in preventing complications in diabetic patients.

  9. Neuroprotective effects of currently used antidotes in tabun-poisoned rats.

    Science.gov (United States)

    Kassa, Jirí; Krejèová, Gabriela

    2003-06-01

    The neuroprotective effects of antidotes (atropine, pralidoxime/atropine, obidoxime/atropine and HI-6/atropine mixtures) on rats poisoned with tabun at a lethal dose (220 microg/kg intramuscularly; 100% of LD50 value) were studied. The tabun-induced neurotoxicity was monitored using a functional observational battery and an automatic measurement of motor activity. The neurotoxicity of tabun was monitored at 24 hr and 7 days after tabun challenge. The results indicate that atropine alone is not able to protect the rats from the lethal effects of tabun. Three non-treated tabun-poisoned rats and one tabun-poisoned rat treated with atropine alone died within 24 hr. On the other hand, atropine combined with all tested oximes allows all tabun-poisoned rats to survive at least 7 days following tabun challenge. Obidoxime combined with atropine seems to be the most effective antidotal treatment for the elimination of tabun-induced neurotoxicity in the case of lethal poisoning among tested antidotal mixtures. The antidotal mixture consisting of atropine and HI-6 is significantly less effective than the combination of atropine with obidoxime in the elimination of tabun-induced neurotoxicity in rats at 24 hr following tabun challenge. Pralidoxime in combination with atropine appears to be practically ineffective to decrease tabun-induced neurotoxicity at 24 hours as well as 7 days following tabun poisoning. Due to its neuroprotective effects, obidoxime seems to be the most effective and most suitable oxime for the antidotal treatment of acute tabun exposure among currently used oximes. Thus, the replacement of obidoxime by a more effective acetylcholinesterase reactivator for soman poisoning, the oxime HI-6, can to a small extent diminish the neuroprotective efficacy of antidotal treatment in the case of acute tabun poisonings.

  10. Neuroprotective effect of RYGB in Zucker fatty diabetic rats

    OpenAIRE

    2014-01-01

    The aim of this study is to explore the therapeutic potential of RYGB, a common used bariatric surgery, on diabetic polyneuropathy (DPN) in streptozotocin (STZ)-induced diabetic rats. In animal model experiments, rats were made diabetic by STZ administration, and after 12 weeks of diabetes, two groups were studied: RYGB and sham surgery control (PF). Change in oral glucose tolerance, insulin sensitivity, and the plasma concentrations of insulin, glucagon, glucagon-like peptide-1 (GLP-1) were ...

  11. Neuroprotective effect of Cucumis melo Var. flexuosus leaf extract on the brains of rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Ibrahim, Doaa S

    2017-02-01

    The central nervous system is one of the most vulnerable organs affected by the oxidative stress associated with diabetes mellitus. Healthy food provides an important source for antioxidants. Therefore, the protective effect of Cucumis melo var. flexuosus (C. melo var. flexuosus) leaf extract on the brains of diabetic rats was investigated. Adult male albino rats divided into 5 groups of 6 rats each were assigned into a normal control group and four diabetic groups. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg bw). One of the four diabetic groups was left untreated and was considered as a diabetic control group while the three other groups were treated with C. melo var. flexuosus leaf extract at the doses of 30, 60 and 120 mg/kg bw for a period of 30 days. After completion of experimental duration plasma and brains were used for evaluating biochemical changes. The obtained data showed that C. melo var. flexuosus leaf extract treatment lowered blood glucose, glycated hemoglobin, brain tumor necrosis factor-alpha, interleukin levels, brain malondialdehyde content and caspase-3 activity. Furthermore, the treatment resulted in a marked increase in plasma dopamine, melatonin, brain vascular endothelial growth factor-A levels, brain catalase and superoxide dismutase activities. From the present study, it can be concluded that the C. melo var. flexuosus leaf extract exerts a neuroprotective effect against oxidative damage associated with diabetes.

  12. Neuroprotection afforded by diazepam against oxygen/glucose deprivation-induced injury in rat cortical brain slices.

    Science.gov (United States)

    Ricci, Lorenzo; Valoti, Massimo; Sgaragli, Giampietro; Frosini, Maria

    2007-04-30

    The aim of the present investigation was to assess neuroprotection exerted by diazepam (0.1-25 microM) in rat cortical brain slices subjected to oxygen-glucose deprivation and reoxygenation. Neuronal injury and neuroprotection were assessed by measuring the release of glutamate and lactate dehydrogenase and tissue water content. Results demonstrate that diazepam exerted neuroprotective effects according to a "U-shaped", hormetic-like, concentration-response curve, with an efficacy window of 0.5-5 microM concentration. Flumazenil (20 microM) fully antagonised neuroprotection afforded by 5 microM diazepam. In conclusion, the hormetic response of diazepam should be taken into consideration when designing experiments aimed at assessing diazepam neuroprotection against ischemia/reoxygenation injury.

  13. Further evidence for the neuroprotective role of oleanolic acid in a model of focal brain hypoxia in rats.

    Science.gov (United States)

    Caltana, Laura; Rutolo, Damián; Nieto, María Luisa; Brusco, Alicia

    2014-12-01

    Ischemic brain injury is a dynamic process involving oxidative stress, inflammation, cell death and the activation of endogenous adaptive and regenerative mechanisms depending on the activation of transcription factors such as hypoxia-inducible factor 1-alpha. Accordingly, we have previously described a new focal hypoxia model by direct intracerebral cobalt chloride injection. In turn, oleanolic acid, a plant-derived triterpenoid, has been extensively used in Asian countries for its anti-inflammatory and anti-tumor properties. A variety of novel pharmacological effects have been attributed to this triterpenoid, including beneficial effects on neurodegenerative disorders--including experimental autoimmune encephalomyelitis--due to its immunomodulatory activities at systemic level, as well as within the central nervous system. In this context, we hypothesize that this triterpenoid may be capable of exerting neuroprotective effects in ischemic brain, suppressing glial activities that contribute to neurotoxicity while promoting those that support neuronal survival. In order to test this hypothesis, we used the intraperitoneal administration of oleanoic acid in adult rats for seven days previous to focal cortical hypoxia induced by cobalt chloride brain injection. We analyzed the neuroprotective effect of oleanoic acid from a morphological point of view, focusing on neuronal survival and glial reaction.

  14. Phenoxybenzamine Is Neuroprotective in a Rat Model of Severe Traumatic Brain Injury

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    Thomas F. Rau

    2014-01-01

    Full Text Available Phenoxybenzamine (PBZ is an FDA approved α-1 adrenergic receptor antagonist that is currently used to treat symptoms of pheochromocytoma. However, it has not been studied as a neuroprotective agent for traumatic brain injury (TBI. While screening neuroprotective candidates, we found that phenoxybenzamine reduced neuronal death in rat hippocampal slice cultures following exposure to oxygen glucose deprivation (OGD. Using this system, we found that phenoxybenzamine reduced neuronal death over a broad dose range (0.1 µM–1 mM and provided efficacy when delivered up to 16 h post-OGD. We further tested phenoxybenzamine in the rat lateral fluid percussion model of TBI. When administered 8 h after TBI, phenoxybenzamine improved neurological severity scoring and foot fault assessments. At 25 days post injury, phenoxybenzamine treated TBI animals also showed a significant improvement in both learning and memory compared to saline treated controls. We further examined gene expression changes within the cortex following TBI. At 32 h post-TBI phenoxybenzamine treated animals had significantly lower expression of pro-inflammatory signaling proteins CCL2, IL1β, and MyD88, suggesting that phenoxybenzamine may exert a neuroprotective effect by reducing neuroinflammation after TBI. These data suggest that phenonxybenzamine may have application in the treatment of TBI.

  15. Neuroprotective effects of daidzein on focal cerebral ischemia injury in rats

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    Adem Bozkurt Aras

    2015-01-01

    Full Text Available Daidzein, a plant extract, has antioxidant activity. It is hypothesized, in this study, that daidzein exhibits neuroprotective effects on cerebral ischemia. Rat models of middle cerebral artery occlusion were intraperitoneally administered daidzein. Biochemical and immunohistochemical tests showed that superoxide dismutase and nuclear respiratory factor 1 expression levels in the brain tissue decreased after ischemia and they increased obviously after daidzein administration; malondialdehyde level and apoptosis-related cysteine peptidase caspase-3 and caspase-9 immunoreactivity in the brain tissue increased after ischemia and they decreased obviously after daidzein administration. Hematoxylin-eosin staining and luxol fast blue staining results showed that intraperitoneal administration of daidzein markedly alleviated neuronal damage in the ischemic brain tissue. These findings suggest that daidzein exhibits neuroprotective effects on ischemic brain tissue by decreasing oxygen free radical production, which validates the aforementioned hypothesis

  16. Neuroprotective effects of daidzein on focal cerebral ischemia injury in rats

    Institute of Scientific and Technical Information of China (English)

    Adem Bozkurt Aras; Mustafa Guven; Tark Akman; Adile Ozkan; Halil Murat Sen; Ugur Duz; Yldray Kalkan; Coskun Silan; Murat Cosar

    2015-01-01

    Daidzein, a plant extract, has antioxidant activity. It is hypothesized, in this study, that daidzein exhibits neuroprotective effects on cerebral ischemia. Rat models of middle cerebral artery oc-clusion were intraperitoneally administered daidzein. Biochemical and immunohistochemical tests showed that superoxide dismutase and nuclear respiratory factor 1 expression levels in the brain tissue decreased after ischemia and they increased obviously after daidzein administra-tion; malondialdehyde level and apoptosis-related cysteine peptidase caspase-3 and caspase-9 immunoreactivity in the brain tissue increased after ischemia and they decreased obviously after daidzein administration. Hematoxylin-eosin staining and luxol fast blue staining results showed that intraperitoneal administration of daidzein markedly alleviated neuronal damage in the ischemic brain tissue. These ifndings suggest that daidzein exhibits neuroprotective effects on ischemic brain tissue by decreasing oxygen free radical production, which validates the afore-mentioned hypothesis.

  17. Neuroprotective effect of cathodal transcranial direct current stimulation in a rat stroke model.

    Science.gov (United States)

    Notturno, Francesca; Pace, Marta; Zappasodi, Filippo; Cam, Etrugul; Bassetti, Claudio L; Uncini, Antonino

    2014-07-15

    Experimental focal brain ischemia generates in the penumbra recurrent depolarizations which spread across the injured cortex inducing infarct growth. Transcranial direct current stimulation can induce a lasting, polarity-specific, modulation of cortical excitability. To verify whether cathodal transcranial direct current stimulation could reduce the infarct size and the number of depolarizations, focal ischemia was induced in the rat by the 3 vessels occlusion technique. In the first experiment 12 ischemic rats received cathodal stimulation (alternating 15 min on and 15 min off) starting 45 min after middle cerebral artery occlusion and lasting 4 h. In the second experiment 12 ischemic rats received cathodal transcranial direct current stimulation with the same protocol but starting soon after middle cerebral artery occlusion and lasting 6 h. In both experiments controls were 12 ischemic rats not receiving stimulation. Cathodal stimulation reduced the infarct volume in the first experiment by 20% (p=0.002) and in the second by 30% (p=0.003). The area of cerebral infarction was smaller in animals receiving cathodal stimulation in both experiments (p=0.005). Cathodal stimulation reduced the number of depolarizations (p=0.023) and infarct volume correlated with the number of depolarizations (p=0.048). Our findings indicate that cathodal transcranial direct current stimulation exert a neuroprotective effect in the acute phase of stroke possibly decreasing the number of spreading depolarizations. These findings may have translational relevance and open a new avenue in neuroprotection of stroke in humans.

  18. The Neuroprotective Effect of Puerarin in Acute Spinal Cord Injury Rats

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    Dapeng Zhang

    2016-08-01

    Full Text Available Background: Acute spinal cord injury (SCI leads to permanent disabilities. This study evaluated the neuroprotective effect of puerarin, a natural extract, in a rat model of SCI. Methods: Acute SCI models were established in rats using a modified Allen's method. Locomotor function was evaluated using the BBB test. The histological changes in the spinal cord were observed by H&E staining. Neuron survival and glial cells activation were evaluated by immunostaining. ELISA and realtime PCR were used to measure secretion and gene expression of cytokines. TUNEL staining was used to examine cell apoptosis and western blot analysis was used to detect protein expression. Results: Puerarin significantly increased BBB score in SCI rats, attenuated histological injury of spinal cord, decreased neuron loss, inhibited glial cells activation, alleviated inflammation, and inhibited cell apoptosis in the injured spinal cords. In addition, the downregulated PI3K and phospho-Akt protein expression were restored by puerarin. Conclusion: Puerarin accelerated locomotor function recovery and tissue repair of SCI rats, which is associated with its neuroprotection, glial cell activation suppression, anti-inflammatory and anti-apoptosis effects. These effects may be associated with the activation of PI3K/Akt signaling pathway.

  19. Neuroprotective activity of peripherally administered liver growth factor in a rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Rafael Gonzalo-Gobernado

    Full Text Available Liver growth factor (LGF is a hepatic mitogen purified some years ago that promotes proliferation of different cell types and the regeneration of damaged tissues, including brain tissue. Considering the possibility that LGF could be used as a therapeutic agent in Parkinson's disease, we analyzed its potential neuroregenerative and/or neuroprotective activity when peripherally administered to unilaterally 6-hydroxydopamine (6-OHDA-lesioned rats. For these studies, rats subjected to nigrostriatal lesions were treated intraperitoneally twice a week with LGF (5 microg/rat for 3 weeks. Animals were sacrificed 4 weeks after the last LGF treatment. The results show that LGF stimulates sprouting of tyrosine hydroxylase-positive terminals and increases tyrosine hydroxylase and dopamine transporter expression, as well as dopamine levels in the denervated striatum of 6-OHDA-lesioned rats. In this structure, LGF activates microglia and raises tumor necrosis factor-alpha protein levels, which have been reported to have a role in neuroregeneration and neuroprotection. Besides, LGF stimulates the phosphorylation of MAPK/ERK1/2 and CREB, and regulates the expression of proteins which are critical for cell survival such as Bcl2 and Akt. Because LGF partially protects dopamine neurons from 6-OHDA neurotoxicity in the substantia nigra, and reduces motor deficits in these animals, we propose LGF as a novel factor that may be useful in the treatment of Parkinson's disease.

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

    Science.gov (United States)

    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

  1. Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats

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    Arijit Ghosh

    2011-01-01

    Full Text Available Objective: To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Materials and Methods: Retention of conditioned avoidance response (CAR and central 5-HT-mediated behavior (lithium-induced head twitches were assessed using repeated electroconvulsive shock (ECS in rats. Rats were divided into eight groups: control (pretreated with distilled water, scopolamine (0.5 mg/kg i.p., ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s pretreated, aspirin (6.75 mg/kg orally pretreated, combined scopolamine and aspirin pretreated, ondansetron (0.36 mg/kg orally pretreated, combined ECS and ondansetron pretreated and combined ECS and aspirin pretreated groups. Data was analyzed by the chi-square test and ANOVA. Results: Findings show that administration of single ECS daily for consecutive 8 days results in enhancement of 5-HT-mediated behavior (lithium-induced head twitches and in disruption of the retention of CAR. Aspirin and ondansetron administration significantly increased the retention of conditioned avoidance response compared to control. Ondansetron and aspirin significantly prevented ECS-induced attenuation of the retention of conditioned avoidance response also. On the other hand, ondansetron and aspirin significantly retarded the ECS-induced enhancement of 5-HT-mediated behavior. Conclusion: Inhibition of the serotonergic transmission by aspirin is responsible for its nootropic and neuroprotective actions.

  2. Neuroprotective Effect of Simvastatin via Inducing the Autophagy on Spinal Cord Injury in the Rat Model

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    Kai Gao

    2015-01-01

    Full Text Available Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, is invariably used to treat cardiovascular diseases. Simvastatin has been recently demonstrated to have a neuroprotective effect in nervous system diseases. The present study aimed to further verify the neuroprotection and molecular mechanism of simvastatin on rats after spinal cord injury (SCI. The expression of Beclin-1 and LC3-B was evidently enhanced at postoperation days 3 and 5, respectively. However, the reduction of the mTOR protein and ribosomal protein S6 kinase p70 subtype (p70S6K phosphorylation level occurred at the same time after SCI. Simvastatin significantly increased the expression of brain-derived neurotrophic factor (BDNF and glial cell line-derived neurotrophic factor (GDNF. Meanwhile, immunofluorescence results indicated that the expression of chondroitin sulfate proteoglycan (CSPG and caspase-3 protein was obviously reduced by simvastatin. Furthermore, Nissl staining and Basso, Beattie, and Bresnahan (BBB scores showed that the quantity and function of motor neurons were visibly preserved by simvastatin after SCI. The findings of this study showed that simvastatin induced autophagy by inhibiting the mTOR signaling pathway and contributed to neuroprotection after SCI.

  3. The cortical response to sensory deprivation in adult rats is affected by gonadectomy.

    Science.gov (United States)

    Mowery, Todd M; Elliott, Kevin S; Garraghty, Preston E

    2009-05-01

    The present study investigated the effects of adult-onset sensory deprivation and gonadectomy. Adult male and female rats underwent unilateral transection of the infraorbital nerve. Half of the subjects had been gonadectomized 1 week prior to the nerve injury. We found that the areas of deprived barrels were significantly reduced when compared to barrels in the contralateral control hemisphere, and that this shrinkage was independent of sex and gonadectomy. We also found significant reductions in cytochrome oxidase staining intensity in the deprived barrels. While there were no differences in the magnitude of this effect between males and females, this effect was substantially more pronounced in the gonadectomized subjects. That is, gonadal hormones appeared to play a significant neuroprotective role in the metabolic response of the barrel cortex to deprivation. Thus, either males and females have a common neuroprotective hormonal pathway, or each has a sex-specific hormone pathway that serves an equivalent neuroprotective function.

  4. Neuroprotective effect of edaravone in experimental glaucoma model in rats: a immunofluorescence and biochemical analysis

    Institute of Scientific and Technical Information of China (English)

    Arzu; Toruk; Aksar; Nursen; Yuksel; Mustafa; Gok; Mustafa; Cekmen; Yusuf; Caglar

    2015-01-01

    AIM: To evaluate the neuroprotective activity of systemically administered edaravone in early and late stage of experimental glaucoma in rats.METHODS: In this study, 60 Wistar albino rats were used. Experimental glaucoma model was created by injecting hyaluronic acid to the anterior chamber once a week for 6wk in 46 of 60 subjects. Fourteen subjects without any medication were included as control group.Edaravone administered intraperitoneally 3 mg/kg/d to the 15 of 30 subjects starting at the onset of glaucoma induction and also administered intraperitoneally3 mg/kg/d to the other 15 subjects starting at three weeks after the onset of glaucoma induction. The other16 subjects who underwent glaucoma induction was administered any therapy. Retinal ganglion cells(RGCs)have been marked with dextran tetramethylrhodamine(DTMR) retrograde at the end of the sixth week and after48 h, subjects were sacrificed by the method of cardiac perfusion. Alive RGC density was assessed in the wholemount retina. Whole-mount retinal tissues homogenized and nitric oxide(NO), malondialdehyde(MDA) and total antioxidant capacity(TAC) values were measured biochemically.RESULTS: RGCs counted with Image-Pro Plus program, in the treatment group were found to be statistically significantly protected, compared to the glaucoma group(Bonferroni,P <0.05). The neuroprotective activity of edaravone was found to be more influential byadministration at the start of the glaucoma process.Statistically significant lower NO levels were determined in the glaucoma group comparing treatment groups(Bonferroni, P <0.05). MDA levels were found to be highest in untreated glaucoma group, TAC levels were found to be lower in the glaucoma induction groups than the control group(Bonferroni, P <0.05).CONCLUSION: Systemic administration of edaravone in experimental glaucoma showed potent neuroprotective activity. The role of oxidative stress causing RGC damage in glaucoma was supported by this study results.

  5. Neuroprotective Effects of Bone Marrow Mesenchymal Stem Cells on Bilateral Common Carotid Arteries Occlusion Model of Cerebral Ischemia in Rat

    Directory of Open Access Journals (Sweden)

    Bagher Pourheydar

    2016-01-01

    Full Text Available Cell therapy is the most advanced treatment of the cerebral ischemia, nowadays. Herein, we discuss the neuroprotective effects of bone marrow mesenchymal stem cells (BMSCs on rat hippocampal cells following intravenous injection of these cells in an ischemia-reperfusion model. Adult male Wistar rats were divided into 5 groups: control, sham (surgery without blockage of common carotid arteries, ischemia (common carotid arteries were blocked for 30 min prior to reperfusion, vehicle (7 days after ischemia PBS was injected via the tail vein, and treatment (injections of BMSC into the tail veins 7 days after ischemia. We performed neuromuscular and vestibulomotor function tests to assess behavioral function and, finally, brains were subjected to hematoxylin and eosin (H&E, anti-Brdu immunohistochemistry, and TUNEL staining. The ischemia group had severe apoptosis. The group treated with BMSCs had a lower mortality rate and also had significant improvement in functional recovery (P<0.001. Ischemia-reperfusion for 30 min causes damage and extensive neuronal death in the hippocampus, especially in CA1 and CA3 regions, leading to several functional and neurological deficits. In conclusion, intravenous injection of BMSCs can significantly decrease the number of apoptotic neurons and significantly improve functional recovery, which may be a beneficial treatment method for ischemic injuries.

  6. Anticonvulsant and neuroprotective effects of Rosa damascena hydro-alcoholic extract on rat hippocampus

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    Mansour Homayoun

    2015-04-01

    Full Text Available Objective: Previously, analgesic, hypnotic, and anticonvulsant effects have been suggested for Rosa damascena (R. damascena. In the present study, possible anti-seizure and neuro-protective effects of hydro-alcoholic extract of R. damascena has been investigated after inducing seizures in rats by pentylenetetrazole (PTZ. Materials and Methods: The rats were divided to five groups: (1 Control: received saline, (2 PTZ: 100 mg/kg, i.p., (3 PTZ-Extract 50 mg/kg(PTZ-Ext 50, (4 PTZ- Extract 100 mg/kg(PTZ-Ext 100, and (5 PTZ- Extract 200 mg/kg(PTZ-Ext 200 groups which were treated with 50, 100, and 200 mg/kg respectively of hydro-alcoholic extract of R. damascena for one week before PTZ injection. The animals were examined for electrocorticography (ECoG recording and finally, the brains were removed for histological study. Results: The hydro-alcoholic extract of R. damascena significantly prolonged the latency of seizure attacks and reduced the frequency and amplitude of epileptiform burst discharges induced by PTZ injection. Moreover, all three doses of the extract significantly inhibited production of dark neurons in different regions of the hippocampus in the mentioned animal model. Conclusion: The present study showed that the hydro-alcoholic extract of R. damascena has anticonvulsant and neuroprotective effects. More investigations are needed to be done in order to better understand the responsible compound(s as well as the possible mechanism(s.

  7. Neuroprotective effects of Schisandrin B against transient focal cerebral ischemia in Sprague-Dawley rats.

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    Lee, Tae Hwa; Jung, Chang Hwa; Lee, Dae-Hee

    2012-12-01

    Fruits of Schisandra have been traditionally used in East Asia for the treatment of dyspnea, cough, dysentery, insomnia, tonic-clonic seizures, and amnesia. Schisandrin B, a dibenzocyclooctadiene derivative isolated from Fructus Schisandrae, has been shown to produce antioxidant effect on rodent liver and heart. In the present study, we investigated the neuroprotective effects of Schisandrin B, a constituent drug of the fruit of Schisandra, against focal cerebral ischemia in rats. Schisandrin B (10, 30 mg/kg, i.p.) was twice administered 30 min before the onset of ischemia and 2h after reperfusion. Schisandrin B 10 and 30 mg/kg treated groups showed infarct volumes reduced by 25.7% and 53.4%, respectively, 2h after occlusion. Also, Schisandrin B treated animal treatment abrogated protein expression of TNF-α and IL-1β and degradation of MMP-2 and MMP-9 in ischemic hemispheres. These results suggest that Schisandrin B treatment provides a neuroprotective effect to rats after transient focal cerebral ischemia by inhibiting inflammation and by protecting against metalloproteinase degradation.

  8. BDNF-secreting capsule exerts neuroprotective effects on epilepsy model of rats.

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    Kuramoto, Satoshi; Yasuhara, Takao; Agari, Takashi; Kondo, Akihiko; Jing, Meng; Kikuchi, Yoichiro; Shinko, Aiko; Wakamori, Takaaki; Kameda, Masahiro; Wang, Feifei; Kin, Kyohei; Edahiro, Satoru; Miyoshi, Yasuyuki; Date, Isao

    2011-01-12

    Brain-derived neurotrophic factor (BDNF) is a well neurotrophic factor with neuroprotective potentials for various diseases in the central nervous system. However several previous studies demonstrated that BDNF might deteriorate symptoms for epilepsy model of animals by progression of abnormal neurogenesis. We hypothesized that continuous administration of BDNF at low dose might be more effective for epilepsy model of animals because high dose of BDNF was used in many studies. BDNF-secreting cells were genetically made and encapsulated for transplantation. Rats receiving BDNF capsule showed significant amelioration of seizure stage and reduction of the number of abnormal spikes at 7 days after kainic acid administration, compared to those of control group. The number of BrdU and BrdU/doublecortin positive cells in the hippocampus of BDNF group significantly increased, compared to that of control group. NeuN positive cells in the CA1 and CA3 of BDNF group were significantly preserved, compared to control group. In conclusion, low dose administration using encapsulated BDNF-secreting cells exerted neuroprotective effects with enhanced neurogenesis on epilepsy model of rats. These results might suggest the importance of the dose and administrative way of this neurotrophic factor to the epilepsy model of animals.

  9. The evaluation of the neuroprotective effects of bispyridinium oximes in tabun-poisoned rats.

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    Kassa, Jiri; Karasova, Jana

    2007-09-01

    Tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) belongs to the group of highly toxic organophosphorus compounds that may be used as chemical warfare agents for military as well as terrorist purposes. Tabun differs from other highly toxic organophosphates by the fact that commonly used antidotes are not able adequately to prevent tabun-induced acute toxic effects. The neuroprotective effects of four bispyridinium oximes (K075, trimedoxime, HI-6, obidoxime) in combination with atropine on rats poisoned with tabun at a sublethal dose (150 microg/kg i.m.; 80% of LD50 value) were studied. Tabun-induced neurotoxicity was monitored using a functional observational battery and automatic measurement of motor activity at 24 h and 7 d following tabun challenge. The results indicated that all tested oximes combined with atropine enabled tabun-poisoned rats to survive 7 d following challenge. Trimedoxime combined with atropine was the most effective antidote in decreasing tabun-induced neurotoxicity in the case of sublethal poisonings among all oximes tested. Due to its neuroprotective effects, trimedoxime may be considered to be more suitable oxime for the antidotal treatment of acute tabun exposure than currently used oximes (obidoxime, HI-6) and the newly synthesized oxime K075.

  10. Neuroprotective efficacy and therapeutic time window of peroxynitrite decomposition catalysts in focal cerebral ischemia in rats#

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    Thiyagarajan, Meenakshisundaram; Kaul, Chaman Lal; Sharma, Shyam Sundar

    2004-01-01

    Free radicals have been implicated in cerebral ischemia reperfusion (IR) injury. Massive production of nitric oxide and superoxide results in continuous formation of peroxynitrite even several hours after IR insult. This can produce DNA strand nicks, hydroxylation and/or nitration of cytosolic components of neuron, leading to neuronal death. Peroxynitrite decomposition catalysts 5,10,15,20-tetrakis(N-methyl-4′-pyridyl)porphyrinato iron (III) (FeTMPyP) and 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III) (FeTPPS) have been demonstrated to protect neurons in in vitro cultures; however, their neuroprotective efficacy in cerebral IR injury has not been explored. In the present study, we investigated the efficacy and the therapeutic time window of FeTMPyP and FeTPPS in focal cerebral ischemia (FCI). FCI was induced according to the middle cerebral artery occlusion (MCAO) method. After 2 h of MCAO and 70 h of reperfusion, the extent of neurological deficits, infarct and edema volume were measured in Sprague–Dawley rats. FeTMPyP and FeTPPS were administered at different time points 2, 6, 9 and 12 h post MCAO. FeTMPyP and FeTPPS (3 mg kg−1, i.v.) treatment at 2 and 6 h post MCAO produced significant reduction in infarct volume, edema volume and neurological deficits. However, treatment at latter time points did not produce significant neuroprotection. Significant reduction of peroxynitrite in blood and nitrotyrosine in brain sections was observed on FeTMPyP and FeTPPS treatment. As delayed treatment of FeTMPyP and FeTPPS produced neuroprotection, we tested whether treatment had any influence over the apoptotic neuronal death. DNA fragmentation and in situ nick end-labeling assays showed that FeTMPyP and FeTPPS treatment reduced IR injury-induced DNA fragmentation. In conclusion, peroxynitrite decomposition catalysts (FeTMPyP and FeTPPS) produced prominent neuroprotection even if administered 6 h post MCAO and the neuroprotective effect is at least in

  11. Neuroprotective Effect of Calpeptin on Acrylamide-Induced Neuropathy in Rats.

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    Wei, Xiaomin; Yan, Fengfeng; E, Meng; Zhang, Cuili; Li, Guozhen; Yang, Xiwei; Zhang, Fengmei; Wang, Shue; Yu, Sufang

    2015-11-01

    Acrylamide (ACR) is a vinyl monomer with established human neurotoxic effects, which is characterized by the accumulation of neurofilaments (NFs) in the distal swellings of large axons in peripheral and central nervous systems. However, the mechanisms of neurotoxicity remain unclear. The objective is to investigate the neuroprotective effect of calpeptin (CP) on ACR-induced neuropathy and its mechanism. Female adult Wistar rats were randomly divided into four groups (control, CP, ACR, and ACR + CP group). Control group received 0.9 % saline, ACR and ACR + CP groups received 30 mg/kg ACR by intraperitoneal injection. In addition, CP and ACR + CP groups also received 200 µg/kg CP. Gait analysis and hind limb splay were measured weekly to analyze neurobehavioral changes. The calpain activity and the changes of NFs protein levels in spinal cord are determined. Compared with control group, body weight of rats in ACR group decreased by 11.3 % (P < 0.01), while in ACR + CP group body weight increased significantly by 8.3 % (P < 0.01) compared with ACR group by the end of the 4th week; gait score of rats in both ACR and ACR + CP groups increased significantly by 167 % and 100 % (P < 0.01) compared with control group, while it decreased significantly by 25.1 % (P < 0.01) in ACR + CP group compared with ACR group; the distance of hind limb splay in both ACR and ACR + CP groups increased by 76.7 % and 49.5 % (P < 0.01) compared with control group, while it decreased by 15.4 % (P < 0.01) in ACR + CP group compared with ACR group; calpain activity of spinal cord at ACR and ACR + CP groups increased significantly by 14.9 % and 10.0 % (P < 0.01) compared with control group, while it decreased 4.2 % (P < 0.01) in ACR + CP group compared with ACR group; compared with control group, the levels of light NF (NF-L), medium NF (NF-M) and heavy NF (NF-H) subunits increased by 81.2 %, 263.6 % and 22.6 % (P < 0.01) in the supernatant of ACR group in spinal cord tissue and increased by 28

  12. Neuroprotective effects of xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), in ischemic stroke of rats.

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    Yen, Ting-Lin; Hsu, Chung-King; Lu, Wan-Jung; Hsieh, Cheng-Ying; Hsiao, George; Chou, Duen-Suey; Wu, Gong-Jhe; Sheu, Joen-Rong

    2012-02-29

    Xanthohumol is the principal prenylated flavonoid in hops (Humulus lupulus L.), an ingredient of beer. Xanthohumol was found to be a potent chemopreventive agent; however, no data are available concerning its neuroprotective effects. In the present study, the neuroprotective activity and mechanisms of xanthohumol in rats with middle cerebral artery occlusion (MCAO)-induced cerebral ischemia were examined. Treatment with xanthohumol (0.2 and 0.4 mg/kg; intraperitoneally) 10 min before MCAO dose-dependently attenuated focal cerebral ischemia and improved neurobehavioral deficits in cerebral ischemic rats. Xanthohumol treatment produced a marked reduction in infarct size compared to that in control rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor (HIF)-1α, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and active caspase-3 protein expressions in ischemic regions. These expressions were obviously inhibited by treatment with xanthohumol. In addition, xanthohumol (3-70 μM) concentration-dependently inhibited platelet aggregation stimulated by collagen (1 μg/mL) in human platelet-rich plasma. An electron spin resonance (ESR) method was used to examine the scavenging activity of xanthohumol on free radicals which had formed. Xanthohumol (1.5 and 3 μM) markedly reduced the ESR signal intensity of hydroxyl radical (OH•) formation in the H₂O₂/NaOH/DMSO system. In conclusion, this study demonstrates for the first time that in addition to its originally being considered an agent preventing tumor growth, xanthohumol possesses potent neuroprotective activity. This activity is mediated, at least in part, by inhibition of inflammatory responses (i.e., HIF-1α, iNOS expression, and free radical formation), apoptosis (i.e., TNF-α, active caspase-3), and platelet activation, resulting in a reduction of infarct volume and improvement in neurobehavior in rats with cerebral ischemia. Therefore, this

  13. Hsp70 inducer, 17-allylamino-demethoxygeldanamycin, provides neuroprotection via anti-inflammatory effects in a rat model of traumatic brain injury

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    Gu, Youquan; Chen, Jun; Wang, Tianhong; Zhou, Chaoning; Liu, Zhaodong; Ma, Lanhua

    2016-01-01

    Traumatic brain injury (TBI) is the predominant cause of mortality in young adults and children living in China. TBI induces inflammatory responses; in addition, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 are important pro-inflammatory cytokines. Considering the observation that Hsp-70 overexpression can exert neuroprotection, identifying a drug that is able to induce the upregulation of Hsp70 has the potential to be a promising therapy for the treatment of neurological diseases. Thus, the present study assessed the clinical effectiveness of an anticancer drug and Hsp70 activator, 17-allylamino-demethoxygeldanamycin (17-AAG), to evaluate its potential as a treatment for patients with TBI. The aim of present study was to determine the neuroprotective effects of 17-AAG following trauma and to investigate the underlying mechanisms of action. To establish rat models, rats were subjected to a controlled cortical impact injury and randomly divided into vehicle or 17-AAG groups. In the 17-AAG group, rats were administered with an intraperitoneal injection of 17-AAG (80 mg/kg) immediately following the establishment of TBI. The motor function was measured using Neurologic Severity Score, and neuronal death was evaluated using immunofluorescence. The expression levels of GLT-1, Bcl-2 and Hsp-70 were detected by western blot analysis and the expression levels of inflammatory cytokines were quantified using ELISA. The present study determined that 17-AAG significantly reduced brain edema and motor neurological deficits (P<0.05), in addition to increasing neuronal survival. The aforementioned findings are associated with a downregulation of the expression levels of pro-inflammatory cytokines TNF-α, IL-1β and IL-6. Conversely, no significant changes of glutamate transporter-1 expression were observed. The present results suggest that 17-AAG treatment may provide a neuroprotective effect by reducing inflammation following TBI.

  14. PI3K/Akt/mTOR pathway participates in neuroprotection by dexmedetomidine inhibits neuronic autophagy following traumatic brain injury in rats

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    Man-He Zhang

    2014-08-01

    Full Text Available Dexmedetomidine (Dex has been demonstrated to provide neuroprotective effect against brain injury in the central nervous system. However, the underlying mechanism of this neuroprotection remains unclear. In this study, we explored whether Dex has the protective potential in rat models of traumatic brain injury(TBI. More importantly, our study further investigated the role of neuronic autophagy induced by PI3K/Akt/mTOR pathway in this neuroprotective action. Adult male Sprague-Dawley rats were subjected to a diffuse cortical impact injury caused by a modified weight-drop device and Dex (15ug/kg, i.v. was administered immediately after TBI. Wet-dry weight method was used to evaluate brain edema. Motor function outcome was assessed by Neurologic Severity Score and the spatial learning ability was evaluated in a Morris water maze. The co-localization of microtubule-associated protein 1 light chain 3(LC3 and neuronal nuclei (NeuN, or LC3 and mammalian target of rapamycin (mTOR were analyzed by immunofluorescence respectively. The expression of LC3, Phosphorylated protein kinase B (p-Akt and p-mTOR were quantified using Western blot analysis. Our results showed treatment of rats exposed to TBI with Dex caused not only marked reduction in cerebral edema, motor and cognitive functions deficits, but also a decrease in LC3 levels and a increase in p-Akt and p-mTOR levels. Taken together, these findings indicated that treatment with Dex after TBI could inhibited neuronic autophagy in the hippocampus mediated by the activation of the PI3K/Akt/mTOR pathway, finally promoting neurological recovery. [Int J Res Med Sci 2014; 2(4.000: 1569-1575

  15. Neuroprotective role of hydralazine in rat spinal cord injury-attenuation of acrolein-mediated damage.

    Science.gov (United States)

    Park, Jonghyuck; Zheng, Lingxing; Marquis, Andrew; Walls, Michael; Duerstock, Brad; Pond, Amber; Vega-Alvarez, Sasha; Wang, He; Ouyang, Zheng; Shi, Riyi

    2014-04-01

    Acrolein, an α,β-unsaturated aldehyde and a reactive product of lipid peroxidation, has been suggested as a key factor in neural post-traumatic secondary injury in spinal cord injury (SCI), mainly based on in vitro and ex vivo evidence. Here, we demonstrate an increase of acrolein up to 300%; the elevation lasted at least 2 weeks in a rat SCI model. More importantly, hydralazine, a known acrolein scavenger can provide neuroprotection when applied systemically. Besides effectively reducing acrolein, hydralazine treatment also resulted in significant amelioration of tissue damage, motor deficits, and neuropathic pain. This effect was further supported by demonstrating the ability of hydralazine to reach spinal cord tissue at a therapeutic level following intraperitoneal application. This suggests that hydralazine is an effective neuroprotective agent not only in vitro, but in a live animal model of SCI as well. Finally, the role of acrolein in SCI was further validated by the fact that acrolein injection into the spinal cord caused significant SCI-like tissue damage and motor deficits. Taken together, available evidence strongly suggests a critical causal role of acrolein in the pathogenesis of spinal cord trauma. Since acrolein has been linked to a variety of illness and conditions, we believe that acrolein-scavenging measures have the potential to be expanded significantly ensuring a broad impact on human health.

  16. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

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    Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  17. Exercise-Induced Neuroprotection in the Spastic Han Wistar Rat: The Possible Role of Brain-Derived Neurotrophic Factor

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    Brooke H. Van Kummer

    2015-01-01

    Full Text Available Moderate aerobic exercise has been shown to enhance motor skills and protect the nervous system from neurodegenerative diseases, like ataxia. Our lab uses the spastic Han Wistar rat as a model of ataxia. Mutant rats develop forelimb tremor and hind limb rigidity and have a decreased lifespan. Our lab has shown that exercise reduced Purkinje cell degeneration and delayed motor dysfunction, significantly increasing lifespan. Our study investigated how moderate exercise may mediate neuroprotection by analyzing brain-derived neurotrophic factor (BDNF and its receptor TrkB. To link BDNF to exercise-induced neuroprotection, mutant and normal rats were infused with the TrkB antagonist K252a or vehicle into the third ventricle. During infusion, rats were subjected to moderate exercise regimens on a treadmill. Exercised mutants receiving K252a exhibited a 21.4% loss in Purkinje cells compared to their controls. Cerebellar TrkB expression was evaluated using non-drug-treated mutants subjected to various treadmill running regimens. Running animals expressed three times more TrkB than sedentary animals. BDNF was quantified via Sandwich ELISA, and cerebellar expression was found to be 26.6% greater in mutant rats on 7-day treadmill exercise regimen compared to 30 days of treadmill exercise. These results suggest that BDNF is involved in mediating exercise-induced neuroprotection.

  18. Acteoside Binds to Caspase-3 and Exerts Neuroprotection in the Rotenone Rat Model of Parkinson's Disease

    Science.gov (United States)

    Wang, Ying; He, Xiao; Zhao, Yuwu

    2016-01-01

    Parkinson’s disease (PD) is characterized by the progressive degeneration of the dopaminergic neurons in the substantia nigra (SN) region. Acteoside has displayed multiple biological functions. Its potential role against PD and the underlying signaling mechanisms are largely unknown. Here, we showed that oral administration of acteoside significantly attenuated parkinsonism symptoms in rotenone-induced PD rats. Further, acteoside inhibited rotenone-induced α-synuclein, caspase-3 upregulation and microtubule-associated protein 2 (MAP2) downregulation in PD rats. The molecular docking and molecular dynamics (MD) simulation results indicated that acteoside may directly bind to and inhibit caspase-3. Acteoside formed hydrogen bonds with at least six residues of caspase-3: ThrA177, SerA178, GlyA238, SerB339, ArgB341 and TrpB348. In addition, a pi-pi interaction was formed between acteoside and caspase-3’s HisA237, which might further stabilize the complex. MD simulation results demonstrated that the binding affinity of the caspase-3-acteoside complex was higher than that of caspase-3 and its native ligand inhibitor. Together, we show that acteoside binds to caspase-3 and exerts neuroprotection in the rotenone rat model of PD. PMID:27632381

  19. Neuroprotective effect of thymoquinone in acrylamide-induced neurotoxicity in Wistar rats

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    Mehri, Soghra; Shahi, Mehran; Razavi, Bibi Marjan; Hassani, Faezeh Vahdati; Hosseinzadeh, Hossein

    2014-01-01

    Objective(s): Acrylamide (ACR) has broad applications in different industries. It also forms in food during heating process. Oxidative stress has a critical role in ACR-induced neurotoxicity in both in vitro and in vivo models; therefore, the aim of the current study was the evaluation of effects of thymoquinone, the main constituent of volatile oil from Nigella sativa seeds in ACR-induced neurotoxicity. Materials and Methods: Male Wistar rats were treated with ACR (50 mg/kg IP) alone or with thymoquinone (TQ) (2.5, 5, 10 mg/kg IP) for 11 days. Two protocols were used in this study, A: in this one TQ and ACR were used simultaneously, B: Administration of TQ was started 1 week before ACR treatment and continued during exposure to ACR. At the end of the treatment, behavioral index (gait score) was examined for rats. After that, rats were sacrificed and molondialdehyde (MDA) as a marker of lipid peroxidation and glutathione (GSH) content were determined in cerebral cortex. Results: Exposure to ACR led to severe gait abnormalities and treatment with TQ significantly decreased abnormalities. Level of MDA was elevated in cerebral cortex after exposure to ACR while TQ treatment significantly and in a dose-dependent manner reduced lipid peroxidation. Results clearly showed that there is no significant difference between two protocols of administration of TQ. Conclusion: It suggests the neuroprotective effect of TQ in this model in part, may be because of due the antioxidant activity of this natural compound. PMID:25859305

  20. Neuroprotective and antioxidant role ofPhoenix dactylifera in permanent bilateral common carotid occlusion in rats

    Institute of Scientific and Technical Information of China (English)

    Rohini R Pujari; Neeraj S Vyawahare; Prasad A Thakurdesai

    2014-01-01

    Objective:To investigate neuroprotective and antioxidant effect ofPhoenix dactylifera (P. dactylifera)(PD) fruits.Methods:Methanolic extract ofP. dactylifera fruits(MEPD) at doses of 30,100 and300 mg/kg was studied against permanentBCCAO(long-term hypoperfusion) in rats. Chronic occlusion of bilateral common carotid arteries(BCCA) caused significant elevation in malondialdehyde levels due to increased lipid peroxidation as well as decrease in levels of other biochemical enzymesi.e. glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferse, catalase and superoxide dismutase.Results:Post occlusion treatment for15 d with 100 and300 mg/kg doses ofMEPD significantly reduced the enhanced malondialdehyde levels and reversed the alterations in the declined levels of antioxidant enzymes in brain homogenates of hypoperfused rats.Long-term cerebral hypoperfusion in rats caused a propensity towards anxiety and restlessness(open field paradigm) accompanied by deficits of spatial learning and memory(Morris water maze testing).Additionally, histopathological observations in hypoperfused brains revealed reactive changes like shrinkage and necrosis of neurons.100 and300 mg/kg doses ofMEPD significantly alleviated these alterations.Conclusions:These results confirmed the protective role ofP. dactylifera in ischemia hypoperfusion and thereby it’s beneficial role in cerebrovascular insufficiency states and related complications.

  1. Hepatoprotection and neuroprotection induced by low doses of IGF-II in aging rats

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    Barhoum Rima

    2011-07-01

    Full Text Available Abstract Background GH and IGFs serum levels decline with age. Age-related changes appear to be associated to decreases in these anabolic hormones. We have previously demonstrated that IGF-I replacement therapy improves insulin resistance, lipid metabolism and reduces oxidative damage (in brain and liver in aging rats. Using the same experimental model, the aim of this work was to study whether the exogenous administration of IGF-II, at low doses, acts analogous to IGF-I in aging rats. Methods Three experimental groups were included in this study: young healthy controls (yCO, 17 weeks old; untreated old rats (O, 103 weeks old; and aging rats treated with IGF-II (O+IGF-II, 2 μg * 100 g body weight-1 * day-1 for 30 days. Analytical parameters were determined in serum by routine laboratory methods using an autoanalyzer (Cobas Mira; Roche Diagnostic System, Basel, Switzerland. Serum levels of hormones (testosterone, IGF-I and insulin were assessed by RIA. Serum Total Antioxidant Status was evaluated using a colorimetric assay. Mitochondrial membrane potential was evaluated using rhodamine 123 dye (adding different substrates to determine the different states. ATP synthesis in isolated mitochondria was determined by an enzymatic method. Results Compared with young controls, untreated old rats showed a reduction of IGF-I and testosterone levels with a decrease of serum total antioxidant status (TAS. IGF-II therapy improved serum antioxidant capability without modifying testosterone and IGF-I circulating concentrations. In addition, IGF-II treatment reduced oxidative damage in brain and liver, improving antioxidant enzyme activities and mitochondrial function. IGF-II was also able to reduce cholesterol and triglycerides levels increasing free fatty acids concentrations. Conclusions We demonstrate that low doses of IGF-II induce hepatoprotective, neuroprotective and metabolic effects, improving mitochondrial function, without affecting testosterone and

  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. Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.

    Directory of Open Access Journals (Sweden)

    Dashdemberel Narantuya

    Full Text Available BACKGROUND AND PURPOSE: Microglia are resident immunocompetent and phagocytic cells of central nervous system (CNS, which produce various cytokines and growth factors in response to injury and thereby regulate disease pathology. The purpose of this study is to investigate the effects of microglial transplantation on focal cerebral ischemia model in rat. METHODS: Transient middle cerebral artery occlusion (MCAO in rats was induced by the intraluminal filament technique. HMO6 cells, human microglial cell line, were transplanted intravenously at 48 hours after MCAO. Functional tests were performed and the infarct volume was measured at 7 and 14 days after MCAO. Migration and cell survival of transplanted microglial cells and host glial reaction in the brain were studied by immunohistochemistry. Gene expression of neurotrophic factors, cytokines and chemokines in transplanted cells and host rat glial cells was determined by laser capture microdissection (LCM and quantitative real time-PCR. RESULTS: HMO6 human microglial cells transplantation group demonstrated significant functional recovery compared with control group. At 7 and 14 days after MCAO, infarct volume was significantly reduced in the HMO group. In the HMO6 group, number of apoptotic cells was time-dependently reduced in the infarct core and penumbra. In addition, number of host rat microglia/macrophages and reactive astrocytes was significantly decreased at 7 and 14 days after MCAO in the penumbra. Gene expression of various neurotrophic factors (GDNF, BDNF, VEGF and BMP7 and anti-inflammatory cytokines (IL4 and IL5 was up-regulated in transplanted HMO6 cells of brain tissue compared with those in culture. The expression of GDNF and VEGF in astrocytes in penumbra was significantly up-regulated in the HMO6 group. CONCLUSIONS: Our results indicate that transplantation of HMO6 human microglial cells reduces ischemic deficits and apoptotic events in stroke animals. The results were mediated

  4. Neuroprotective effect of estrogen after chronic spinal cord injury in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: At present, there is still lack of effective drugs for chronic spinal cord injury, whereas it is found recently that estrogen has a neuroprotective effect on brain and spinal cord injuries.OBJECTIVE: To observe the effect of estrogen on the apoptosis of nerve cells after gradual chronic spinal cord injury in ovariectomized rats.DESIGN: A randomized controlled animal trial.SETTING: Institute of Orthopaedics, the Second Hospital of Lanzhou University.MATERIALS: Sixty-five female Wistar rats of common degree, weighing 220 - 250 g, were provided by the experimental animal center of Lanzhou University. The rats were randomly divided into sham-operated group (n =5), estrogen-treated group (n =30) and saline control group (n =30), and the latter two groups were observed at 1, 3, 7, 14, 28 and 60 days respectively, and 5 rats for each time point.METHODS: All the rats were treated with bilateral oophorectomy 2 weeks before the experiment. T10 vertebral lamina was revolved into using plastic screw. The spinal canal impingement was not induced initially. After that, the original incision was opened to expose the screw every 7 - 10 days.MAIN OUTCOME MEASURES: The apoptosis and Caspase-3 positive cells in the damaged spinal cord were detected using terminal deoxynucleotidal transferase-mediated dUTP-biotin nick end labeling (TUNEL) method and Caspase-3 immunohistochemical staining at 1, 3, 7, 14, 28 and 60 days after chronic spinal cord injury respectively.RESULTS: Totally 65 rats were used, and the deleted ones during the experiment were supplemented by others. Changes of Caspase-3 expression after spinal cord injury: In the sham-operated group, only a small amount of Caspase-3 proteins were observed in the rat spinal cord, mainly located in motor neurons of spinal cord anterior horn. In the estrogen-treated group and saline control group, positive cells expressed occasionally at 1 day postoperatively, began to increase obviously at 7 days after injury, strongly

  5. Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease

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    Harry V. Vinters

    2010-11-01

    Full Text Available Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism that is altered by inhibitors of complex I and has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, we investigated the effects of mildronate in a rat model of Parkinson’s disease (PD that was generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6‑OHDA. We assessed the expression of cell biomarkers that are involved in signaling cascades and provide neural and glial integration: the neuronal marker TH (tyrosine hydroxylase; ubiquitin (a regulatory peptide involved in the ubiquitin-proteasome degradation system; Notch-3 (a marker of progenitor cells; IBA-1 (a marker of microglial cells; glial fibrillary acidic protein, GFAP (a marker of astrocytes; and inducible nitric oxide synthase, iNOS (a marker of inflammation. The data show that in the 6-OHDA-lesioned striatum, mildronate completely prevented the loss of TH, stimulated Notch-3 expression and decreased the expression of ubiquitin, GFAP and iNOS. These results provide evidence for the ability of mildronate to control the expression of an array of cellular proteins and, thus, impart multi-faceted homeostatic mechanisms in neurons and glial cells in a rat model of PD. We suggest that the use of mildronate provides a protective effect during the early stages of PD that can delay or halt the progression of this neurodegenerative disease.

  6. The Neuroprotective Effect of Gugijihwang-Tang on Trimethyltin-Induced Memory Dysfunction in the Rat

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    Eun-Yee Jung

    2013-01-01

    Full Text Available Gugijihwang-Tang (the herbal formula PM012, a decoction consisting of several herbs including Rehmanniae Radix Preparata, has been widely used as herbal treatment for dementia. In order to investigate the neuroprotective action of this prescription, we examined the effect of Gugijihwang-Tang on learning and memory using the Morris water maze and [F-18]FDG micro PET neuroimaging technique. After injection of trimethyltin (TMT, 8.0 mg/kg, i.p., which is a potent toxicant that selectively kills cells in the central nervous system, rats were administered Gugijihwang-Tang (100 mg/kg, p.o. daily for two weeks, followed by the Morris water maze tasks and [F-18]FDG micro PET neuroimaging. In Gugijihwang-Tang administered TMT-treated rats, they showed improved learning and memory abilities in water maze tasks and glucose metabolism, suggesting that Gugijihwang-Tang plays effectively positive role in the improvement of brain function including learning and memory after TMT-induced neurodegeneration. Taken together, our results suggested that the Gugijihwang-Tang should be useful for developing strategies protecting nervous system and improving brain function.

  7. Inhibition of Sirtuin 2 exerts neuroprotection in aging rats with increased neonatal iron intake

    Institute of Scientific and Technical Information of China (English)

    Xijin Wang; Meihua Wang; Liu Yang; Jie Bai; Zhiqiang Yan; Yuhong Zhang; Zhenguo Liu

    2014-01-01

    Impaired iron homeostasis may cause damage to dopaminergic neurons and is critically involved in the pathogenesis of Parkinson’s disease. At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals. Therefore, we hypothesized that increased neonatal iron intake would result in signiifcant behavior abnormalities and striatal dopamine depletion during aging, and Sirtuin 2 contributes to the age-related neurotoxicity. In the present study, we observed that neonatal iron intake (120 μg/g per day) during postnatal days 10–17 resulted in significant behavior abnormalities and striatal dopamine depletion in aging rats. Furthermore, after AK-7 (a selective Sirtuin 2 inhibitor) was injected into the substantia nigra at postnatal 540 days and 570 days (5 μg/side per day), striatal dopamine depletion was signiifcant-ly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental ifndings suggest that increased neonatal iron intake may result in Parkinson’s dis-ease-like neurochemical and behavioral deifcits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson’s disease.

  8. Inhibition of autophagy contributes to ischemic postconditioning-induced neuroprotection against focal cerebral ischemia in rats.

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    Li Gao

    Full Text Available BACKGROUND: Ischemic postconditioning (IPOC, or relief of ischemia in a stuttered manner, has emerged as an innovative treatment strategy to reduce programmed cell death, attenuate ischemic injuries, and improve neurological outcomes. However, the mechanisms involved have not been completely elucidated. Recent studies indicate that autophagy is a type of programmed cell death that plays elusive roles in controlling neuronal damage and metabolic homeostasis. This study aims to determine the role of autophagy in IPOC-induced neuroprotection against focal cerebral ischemia in rats. METHODOLOGY/PRINCIPAL FINDINGS: A focal cerebral ischemic model with permanent middle cerebral artery (MCA occlusion plus transient common carotid artery (CCA occlusion was established. The autophagosomes and the expressions of LC3/Beclin 1/p62 were evaluated for their contribution to the activation of autophagy. We found that autophagy was markedly induced with the upregulation of LC3/Beclin 1 and downregulation of p62 in the penumbra at various time intervals following ischemia. IPOC, performed at the onset of reperfusion, reduced infarct size, mitigated brain edema, inhibited the induction of LC3/Beclin 1 and reversed the reduction of p62 simultaneously. Rapamycin, an inducer of autophagy, partially reversed all the aforementioned effects induced by IPOC. Conversely, autophagy inhibitor 3-methyladenine (3-MA attenuated the ischemic insults, inhibited the activation of autophagy, and elevated the expression of anti-apoptotic protein Bcl-2, to an extent comparable to IPOC. CONCLUSIONS/SIGNIFICANCE: The present study suggests that inhibition of the autophagic pathway plays a key role in IPOC-induced neuroprotection against focal cerebral ischemia. Thus, pharmacological inhibition of autophagy may provide a novel therapeutic strategy for the treatment of stroke.

  9. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats.

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    Neetu Kushwah

    Full Text Available Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH in Unpredictable Chronic Mild Stress (UCMS induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM, open field test (OFT, force swim test (FST, as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state.

  10. Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study

    OpenAIRE

    Yablonsky-Alter, Elena; Agovic, Mervan S.; Gashi, Eleonora; Lidsky, Theodore I.; Friedman, Eitan; Banerjee, Shailesh P.

    2009-01-01

    Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate and neuroprotective taurine in the rat striatum by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine exposure markedly...

  11. Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats.

    Science.gov (United States)

    Fatani, Amal Jamil; Al-Rejaie, Salim Salih; Abuohashish, Hatem Mustafa; Al-Assaf, Abdullah; Parmar, Mihir Yogeshkumar; Ola, Mohammad Shamsul; Ahmed, Mohammed Mahboobuddin

    2015-05-01

    and NGF was also ameliorated by Gs treatment. Histological analysis indicated that Gs corrected the sciatic tissue in the diabetic rats. Therefore, the results demonstrated that the neuroprotective effect of Gs may be associated with the inhibitory effect on the excessive activation of inflammatory molecules and oxidative stress mediators.

  12. TFP5 peptide, derived from CDK5-activating cofactor p35, provides neuroprotection in early-stage of adult ischemic stroke

    Science.gov (United States)

    Ji, Ya-Bin; Zhuang, Pei-Pei; Ji, Zhong; Wu, Yong-Ming; Gu, Yong; Gao, Xiao-Ya; Pan, Su-Yue; Hu, Ya-Fang

    2017-01-01

    Cyclin-dependent kinase 5 (CDK5) is a multifaceted protein shown to play important roles in the central nervous system. Abundant evidence indicates that CDK5 hyperactivities associated with neuronal apoptosis and death following ischemic stroke. CDK5 activity increases when its cofactor p35 cleaves into p25 during ischemia. Theoretically, inhibition of CDK5/p25 activity or reduction of p25 would be neuroprotective. TFP5, a modified 24-aa peptide (Lys254-Ala277) derived from p35, was found to effectively inhibit CDK5 hyperactivity and improve the outcomes of Alzheimer’s disease and Parkinson’s disease in vivo. Here, we showed that intraperitoneal injection of TFP5 significantly decreased the size of ischemia in early-stage of adult ischemic stroke rats. Relative to controls, rats treated with TFP5 displayed reduced excitotoxicity, neuroinflammation, apoptosis, astrocytes damage, and blood-brain barrier disruption. Our findings suggested that TFP5 might serve as a potential therapeutic candidate for acute adult ischemic stroke. PMID:28045138

  13. Effect of HDAC inhibitors on neuroprotection and neurite outgrowth in primary rat cortical neurons following ischemic insult.

    Science.gov (United States)

    Hasan, Mohammad Rakibul; Kim, Ji-Hye; Kim, Youn Jung; Kwon, Kyoung Ja; Shin, Chan Young; Kim, Hahn Young; Han, Seol-Heui; Choi, Dong-Hee; Lee, Jongmin

    2013-09-01

    Histone deacetylase inhibitors (HDACi)-valproic acid (VPA) and trichostatin A (TSA) promote neurogenesis, neurite outgrowth, synaptic plasticity and neuroprotection. In this study, we investigated whether VPA and TSA promote post-ischemic neuroprotection and neuronal restoration in rat primary cortical neurons. On 6 days in vitro (DIV), cortical neurons were exposed to oxygen-glucose deprivation for 90 min. Cells were returned to normoxic conditions and cultured for 1, 3, or 7 days with or without VPA and TSA. Control cells were cultured in normoxic conditions only. On 7, 9, and 13 DIV, cells were measured neurite outgrowth using the Axiovision program and stained with Tunel staining kit. Microtubule associated protein-2 immunostaining and tunel staining showed significant recovery of neurite outgrowth and post-ischemic neuronal death by VPA or TSA treatment. We also determined levels of acetylated histone H3, PSD95, GAP 43 and synaptophysin. Significant increases in all three synaptic markers and acetylated histone H3 were observed relative to non-treated cells. Post-ischemic HDACi treatment also significantly raised levels of brain derived neurotrophic factor (BDNF) expression and secreted BDNF. Enhanced BDNF expression by HDACi treatment might have been involved in the post-ischemic neuroprotection and neuronal restorative effects. Our findings suggest that both VPA and TSA treatment during reoxygenation after ischemia may help post-ischemic neuroprotection and neuronal regeneration via increased BDNF expression and activation.

  14. Neuroprotective effects of Kaempferide-7-O-(4″-O-acetylrhamnosyl)-3-O-rutinoside on cerebral ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Wang, Shuaijun; Xu, Huali; Xin, Ying; Li, Maowei; Fu, Wenwen; Wang, Yuchen; Lu, Zeyuan; Yu, Xiaofeng; Sui, Dayun

    2016-10-05

    In the present study, we aim to evaluate the potential neuroprotective effect and the underlying mechanism of Kaempferide-7-O-(4″-O-acetylrhamnosyl)-3-O-rutinoside (A-F-B) against cerebral I/R injury. Adult male rats were pretreated with A-F-B by intragastric administration once a day for 3 days. One hour after the third day administration, animals were subjected to 2h of transient middle cerebral artery occlusion (MCAO) followed by 24h of reperfusion. Neurological deficit, infarct volume, histopathological changes, oxidative stress-related biochemical parameters, neuronal apoptosis, apoptosis-related proteins and the expression of pro-inflammator cytokines genes were measured. A-F-B significantly decreased neurological and histological deficits, reduced the infarct volume, and decreased neuroapoptosis. Meanwhile, A-F-B inhibited the expression of Bax, cleaved caspase-3, cleaved caspase-9, and promoted Bcl-2 expression. In addition, the expression of pro-inflammator cytokines, including phospho-NF-kBp65, interleukin-1β, interleukin-6, tumor necrosis factor-α, intercellular adhesion molecule-1, cyclooxygenase-2 and inducible nitric oxide synthase, were also suppressed by A-F-B pretreatment. Furthermore, pretreatment with A-F-B could significantly increase the activities of superoxide dismutase, glutathione peroxidase, but decrease the content of malondiadehyde in blood serum. These results suggest that A-F-B has the neuroprotective effect in ischemic stroke by suppressing neuroinflammation, reactive oxygen species and neuroapoptosis.

  15. Combined prostaglandin E1 and lithium exert potent neuroprotection in a rat model of cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Rui SHENG; Li-sha ZHANG; Rong HAN; Bo GAO; Xiao-qian LIU; Zheng-hong QIN

    2011-01-01

    Alm: To examine the effects of a mixed formulation composed of prostaglandin E1 and lithium (PGE1+Li mixture) on brain damage after cerebral ischemia. The effects of the mixture on protein expression of heat shock proteins (HSPs), p53, and Bcl-2 were also determined.Methods: Brain ischemia was induced with a permanent middle cerebral artery occlusion (pMCAO) in rats. Rats were treated with a single intravenous administration of PGE1, lithium or a PGE1+Li mixture immediately after the ischemic insult. The infarct volume and motor behavior deficits were analyzed 24 h after the ischemic insult. The protein levels of HSP70, glucose-regulated protein 78 (GRP78), HSP60, Bcl-2, and p53 in the striatum of the ipsilateral hemisphere were examined using immunoblotting.Results: The mixture (PGE1 22.6 nmol/kg+Li 0.5 mmol/kg) reduced infarct volume and neurological deficits induced by focal cerebral ischemia. Moreover, the mixture had a greater neuroprotective effect against cerebral ischemia compared with PGE1 or lithium alone.The mixture was effective even if it was administered 3 h after ischemia. PGE1+Li also significantly upregulated cytoprotective HSP70,GRP78, HSP60, and Bcl-2 protein levels, while decreasing p53 expression.Conclusion: These results demonstrated a PGE1+Li mixture with a therapeutic window of up to 3 h for clinical treatment of cerebral ischemia. The PGE1+Li mixture potentially exerts a protective effect after stroke through the induction of HSPs and Bcl-2 proteins.

  16. Verapamil augments the neuroprotectant action of berberine in rat model of transient global cerebral ischemia.

    Science.gov (United States)

    Singh, Dhirendra Pratap; Chopra, Kanwaljit

    2013-11-15

    Various potential molecules with putative positive role in stroke pathology have failed to confer neuro-protection in animal models due to their insufficient bioavailability in brain. Efflux of these molecules by P-glycoprotein (P-gp), on blood brain barrier (BBB) is one of the reasons of their poor bioavailability. Berberine, have anti-inflammatory, antioxidant, anti-apoptotic properties, but also having low oral bioavailabilty. Verapamil, which increased the central nervous system uptake of few drugs, when concomitantly administered with berberine was evaluated in this animal model. Wistar rats were subjected to bilateral common carotid artery occlusion to induce acute cerebral ischemia for 15 min followed by reperfusion resulting in transient global cerebral ischemia. For 19 days berberine (5, 10, 20mg/kg, p.o.) alone and in similar doses concomitantly with verapamil (2mg/kg, p.o.) was evaluated employing various neuro-behavioral test, biochemical parameters and molecular estimations. The adjunction of berberine with verapamil improved the neurological outcome in a battery of behavioral paradigms, improved spatial memory in Morris water maze task, ameliorated the oxidative-nitrosative stress, increased acetylcholinesterase (AChE) activity, as well as improved mitochondrial complex (I, II, and IV) activity, reducing tumor necrosis factor-alpha, interleukin-1 beta and caspase-3 levels in brain tissues as compared to berberine alone group in ischemic rats. There is a strong possibility of improved brain bioavailabity of berberine when combined with verapamil. The findings suggested that the combination of berberine with verapamil, which could enhance its brain uptake, will surely provide a greater impact in neroprotection drug discovery for search of such combination.

  17. Neuroprotective effects of L-carnitine against oxygenglucose deprivation in rat primary cortical neurons

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    Yu Jin Kim

    2012-07-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Hypoxic-ischemic encephalopathy is an important cause of neonatal mortality, as this brain injury disrupts normal mitochondrial respiratory activity. Carnitine plays an essential role in mitochondrial fatty acid transport and modulates excess acyl coenzyme A levels. In this study, we investigated whether treatment of primary cultures of rat cortical neurons with L-carnitine was able to prevent neurotoxicity resulting from oxygen-glucose deprivation (OGD. &lt;b&gt;Methods:&lt;/b&gt; Cortical neurons were prepared from Sprague-Dawley rat embryos. L-Carnitine was applied to cultures just prior to OGD and subsequent reoxygenation. The numbers of cells that stained with acridine orange (AO and propidium iodide (PI were counted, and lactate dehydrogenase (LDH activity and reactive oxygen species (ROS levels were measured. The 3-(4,5-dimethylthiazol-2-yl-2,5- diphenyltetrazolium bromide assay and the terminal uridine deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were performed to evaluate the effect of L-carnitine (1 μM, 10 μM, and 100 μM on OGD-induced neurotoxicity. &lt;B&gt;Results:&lt;/b&gt; Treatment of primary cultures of rat cortical neurons with L-carnitine significantly reduced cell necrosis and prevented apoptosis after OGD. L-Carnitine application significantly reduced the number of cells that died, as assessed by the PI/AO ratio, and also reduced ROS release in the OGD groups treated with 10 μM and 100 μM of L-carnitine compared with the untreated OGD group (P&lt;0.05. The application of L-carnitine at 100 μM significantly decreased cytotoxicity, LDH release, and inhibited apoptosis compared to the untreated OGD group (P&lt;0.05. &lt;B&gt;Conclusion:&lt;/b&gt; L-Carnitine has neuroprotective benefits against OGD in rat primary cortical neurons in vitro.

  18. Neuroprotective effects of recombinant human erythropoietin on facial motoneurons after facial nerve injury in rats

    Institute of Scientific and Technical Information of China (English)

    Yubing Dai; Wenlong Luo; Hongjiang Chen; Jianghua Nie; Li Fang; Xiaofei Lai; Jingjing Li

    2008-01-01

    BACKGROUND: Erythropoietin and recombinant human erythropoietin (rhEPO) inhibit apoptosis of motor neurons caused by spinal cord injury and brain damage in rats. However, it still remains to be shown whether rhEPO can protect facial motoneurons (FMNs) as well.OBJECTIVE: To test the neuroprotective effects of rhEPO on injured FMNs, as well as the influence on Caspase-3 expression.DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. This study was performed at the Central Laboratory of Basic Medical College, Chongqing Medical University from January to October 2007.MATERIALS: Seventy-five female SD rats, weighing 210-230g. rhEPO injection was provided by Sansheng pharmaceuticals company, Shenyang City, Liaoning Province, China, and the License number was HMLN S20010001.METHODS: A total of 75 female rats were randomly divided into rhEPO treatment, control, and sham operation groups, with 25 rats in each group. Rat models of facial nerve injury were established in the rhEPO treatment group and the control group by crushing the main trunk of the left facial nerve. Surgical microscopic observation of the facial nerve damage displayed perineurial disruption. The left stylomastoid foramen of the sham operation group were only exposed, but without nerve injury. The rhEPO treatment group was treated with rhEPO (5000U/kg, i. p.) once following injury and once a day for two weeks. The control and sham operation groups were treated with the same dose of normal saline (i. p.), once following injury and once a day for two weeks.MAIN OUTCOME MEASURES: Rats were sacrificed 3, 7, 14, 21, and 28 days after injury, FMN survival after facial nerve injury was analyzed by Toluidine blue staining, and then survival ratios (L/R) were calculated. The number of apoptotic profiles in the injured FMNs were evaluated by TUNEL staining. Expression of Caspase-3 in the facial nucleus was detected by immunohistochemistry methods.RESULTS: A total of 75 rats were included in the final

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

  20. Basic fibroblast growth factor protects against excitotoxicity and chemical hypoxia in both neonatal and adult rats.

    Science.gov (United States)

    Kirschner, P B; Henshaw, R; Weise, J; Trubetskoy, V; Finklestein, S; Schulz, J B; Beal, M F

    1995-07-01

    Basic fibroblast growth factor (bFGF) is a polypeptide growth factor that promotes neuronal survival. We recently found that systemic administration of bFGF protects against both excitotoxicity and hypoxia-ischemia in neonatal animals. In the present study, we examined whether systemically administered bFGF could prevent neuronal death induced by intrastriatal injection of N-methyl-D-aspartate (NMDA) or chemical hypoxia induced by intrastriatal injection of malonate in adult rats and 1-methyl-4-phenylpyridinium (MPP+) in neonatal rats. Systemic administration of bFGF (100 micrograms/kg) for three doses both before and after intrastriatal injection of either NMDA or malonate in adult rats produced a significant neuroprotective effect. In neonatal rats, bFGF produced dose-dependent significant neuroprotective effects against MPP+ neurotoxicity, with a maximal protection of approximately 50% seen with either a single dose of bFGF of 300 micrograms/kg or three doses of 100 micrograms/kg. These results show that systemic administration of bFGF is effective in preventing neuronal injury under circumstances in which the blood-brain barrier may be compromised, raising the possibility that this strategy could be effective in stroke.

  1. In vivo investigation of the neuroprotective property of Convolvulus pluricaulis in scopolamine-induced cognitive impairments in Wistar rats

    Directory of Open Access Journals (Sweden)

    Syed Waseem Bihaqi

    2011-01-01

    Full Text Available Aim : To investigate the neuroprotective effect of Convolvulus pluricaulis aqueous extract (AE against scopolamine (1 mg/kg body weight (bwt-induced neurotoxicity in the cerebral cortex of male Wistar rats. Materials and Methods : The study was carried out on male Wistar rats (age matched, weight 250 ± 20 g. The present study investigated cognitive-enhancing property of AE using Elevated plus maze (EPM (transfer latency [TL] and Morris water maze (MWM. Besides evaluating the effect of extract on neurochemical enzymes, in vivo antioxidant and free radical scavenging activities were also screened. All the measured parameters were compared with rivastigmine tartrate (1 mg/kg bwt which was taken as standard. Results : Pretreatment of rats with AE (150 mg/kg bwt significantly reduced scopolamine-induced increase in the TL in EPM, whereas in MWM, administration of extract improved the impairment of spatial memory induced by scopolamine. The activity of acetylcholinesterase (AChE was significantly inhibited by extract within the cortex and hippocampus. Reduced activities or contents of glutathione reductase, superoxide dismutase, and reduced glutathione within the cortex and hippocampus induced by scopolamine were elevated by the extract. Taken together, it could be postulated that extract may exert its potent-enhancing activity through both anti-AChE and antioxidant action. Conclusion : AE possesses neuroprotective potential, thus validating its use in alleviating toxic effects of scopolamine.

  2. Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons

    Directory of Open Access Journals (Sweden)

    Ullah Ikram

    2012-01-01

    Full Text Available Abstract Background Exposure to ethanol during early development triggers severe neuronal death by activating multiple stress pathways and causes neurological disorders, such as fetal alcohol effects or fetal alcohol syndrome. This study investigated the effect of ethanol on intracellular events that predispose developing neurons for apoptosis via calcium-mediated signaling. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in ethanol neurotoxicity. The present study was designed to evaluate the neuroprotective mechanisms of metformin (Met and thymoquinone (TQ during ethanol toxicity in rat prenatal cortical neurons at gestational day (GD 17.5. Results We found that Met and TQ, separately and synergistically, increased cell viability after ethanol (100 mM exposure for 12 hours and attenuated the elevation of cytosolic free calcium [Ca2+]c. Furthermore, Met and TQ maintained normal physiological mitochondrial transmembrane potential (ΔψM, which is typically lowered by ethanol exposure. Increased cytosolic free [Ca2+]c and lowered mitochondrial transmembrane potential after ethanol exposure significantly decreased the expression of a key anti-apoptotic protein (Bcl-2, increased expression of Bax, and stimulated the release of cytochrome-c from mitochondria. Met and TQ treatment inhibited the apoptotic cascade by increasing Bcl-2 expression. These compounds also repressed the activation of caspase-9 and caspase-3 and reduced the cleavage of PARP-1. Morphological conformation of cell death was assessed by TUNEL, Fluoro-Jade-B, and PI staining. These staining methods demonstrated more cell death after ethanol treatment, while Met, TQ or Met plus TQ prevented ethanol-induced apoptotic cell death. Conclusion These findings suggested that Met and TQ are strong protective agents against ethanol

  3. [Study of acetylsalicylic acid role in the potentiation of antiamnesic and neuroprotective properties of piracetam in rats with alloxan diabetes].

    Science.gov (United States)

    Zhiliuk, V I; Levykh, A E; Mamchur, V I

    2013-01-01

    It has been established that prolonged alloxan-induced hyperglycemia in rats potentiates amnesic properties of scopolamine hydrobromide. It was characterized by shortening of the latent period by 44% (ppiracetam with acetylsalicylic acid was accompanied by an expressed antiamnetic potential - the reduction of early markers of proteins degradation (aldehydephenylhydrazones, APH) by 21,7% (ppiracetam according to the effect upon KPH. NO2-/NO3- level was also decreased by 30,3% (ppiracetam may be assumed to be directly related to the ability of acetylsalicylic acid to improve microcirculation in the ischemic areas of the brain in diabetes and probably to its neuroprotective potential.

  4. Superior neuroprotective effects of cerebrolysin in heat stroke following chronic intoxication of Cu or Ag engineered nanoparticles. A comparative study with other neuroprotective agents using biochemical and morphological approaches in the rat.

    Science.gov (United States)

    Sharma, Hari Shanker; Muresanu, Dafin Fior; Patnaik, Ranjana; Stan, Adina Dora; Vacaras, Vitalie; Perju-Dumbrav, Laura; Alexandru, Badisor; Buzoianu, Anca; Opincariu, Iulian; Menon, Preeti Kumaran; Sharma, Aruna

    2011-09-01

    The possibility that cerebrolysin, a mixture of several active fragments of neurotrophic factors and peptides induces neuroprotection following nanoparticles induced exacerbation of brain damage in heat stroke was examined in a rat model. For this purpose, the therapeutic efficacy of Cerebrolysin (2.5 or 5 ml/kg) recommended for stroke treatment was used in comparison with other drugs in standard doses recommended for such therapy in clinical situations e.g., levetiracetam (44 mg/kg), pregabalin (200 mg/kg), topiramate (40 mg/kg,i.p.) and valproate (400 mg/kg). Rats subjected to 4 h heat stress in a biological oxygen demand (BOD) incubator at 38 degrees C (Rel Humid 45-47%; Wind vel 22.4 to 25.6 cm/sec) developed profound behavioral symptoms of heat stroke e.g., hyperthermia, profuse salivation, prostration and gastric ulcerations in the stomach. These rats also exhibited marked brain pathology at this time. Thus, breakdown of the blood-brain barrier (BBB) to proteins associated with brain edema formation could be seen in these heat stressed rats as compared to control groups. The edematous brain areas showed profound neuronal damage and/or distortion in large areas of the neuropil. These pathological symptoms were further exacerbated in Cu or Ag nanoparticles treated group (50-60 nm particle size, 50 mg/kg, i.p./day for 7 days) after identical heat stress on the 8th day. Pretreatment with cerebrolysin (2.5 ml/kg, i.v.) daily for 3 days in normal rats before heat stress significantly reduced the behavioral stress symptoms and the breakdown of the BBB function, edema formation and neuronal injuries. However, the magnitude and intensity of these neuroprotective effects were much less intense in all other drug treated rats after similar heat stress. On the other hand, almost double dose of cerebrolysin (5 ml/kg) was needed to achieve comparable neuroprotection in nanoparticles treated animals after heat stress. Whereas, double dose of all other compounds was much less

  5. Resveratrol increases antioxidant defenses and decreases proinflammatory cytokines in hippocampal astrocyte cultures from newborn, adult and aged Wistar rats.

    Science.gov (United States)

    Bellaver, Bruna; Souza, Débora Guerini; Souza, Diogo Onofre; Quincozes-Santos, André

    2014-06-01

    Astrocytes are responsible for modulating neurotransmitter systems and synaptic information processing, ionic homeostasis, energy metabolism, maintenance of the blood-brain barrier, and antioxidant and inflammatory responses. Our group recently published a culture model of cortical astrocytes obtained from adult Wistar rats. In this study, we established an in vitro model for hippocampal astrocyte cultures from adult (90 days old) and aged (180 days old) Wistar rats. Resveratrol, a polyphenol found in grapes and red wine, exhibits antioxidant, anti-inflammatory, anti-aging and neuroprotective effects that modulate glial functions. Here, we evaluated the effects of resveratrol on GSH content, GS activity, TNF-α and IL-1β levels in hippocampal astrocytes from newborn, adult and aged Wistar rats. We observed a decrease in antioxidant defenses and an increase in the inflammatory response in hippocampal astrocytes from adult and aged rats compared to classical astrocyte cultures from newborn rats. Resveratrol prevented these effects. These findings reinforce the neuroprotective effects of resveratrol, which are mainly associated with antioxidant and anti-inflammatory activities.

  6. A comparison of the neuroprotective efficacy of individual oxime (HI-6) and combinations of oximes (HI-6+trimedoxime, HI-6+K203) in soman-poisoned rats.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Tesarova, Sandra

    2011-07-01

    The ability of two combinations of oximes (HI-6+trimedoxime, HI-6+K203) to reduce soman-induced acute neurotoxic signs and symptoms was compared with the neuroprotective efficacy of the oxime HI-6 alone, using a functional observational battery. Soman-induced neurotoxicity and the neuroprotective effects of HI-6 alone and HI-6 combined with trimedoxime or K203 in rats poisoned with soman at a sublethal dose (90 μg/kg intramuscularly, i.m.; 80% of LD₅₀ value) were monitored by the functional observational battery at 24 hours following soman administration. The results indicate that both tested oxime mixtures combined with atropine were able to allow soman-poisoned rats to survive 24 hours following soman challenge, while 4 nontreated soman-poisoned rats and 1 soman-poisoned rat treated with oxime HI-6 alone combined with atropine died within 24 hours following soman poisoning. While the oxime HI-6 alone combined with atropine treatment was able to eliminate a few soman-induced neurotoxic signs and symptoms, both oxime mixtures showed higher neuroprotective efficacy in soman-poisoned rats. Especially, the combination of HI-6 with trimedoxime was able to eliminate most soman-induced neurotoxic signs and symptoms and markedly reduce acute neurotoxicity of soman in rats. Thus, both tested mixtures of oximes combined with atropine were able to increase the neuroprotective effectiveness of antidotal treatment of acute soman poisonings, compared to the individual oxime.

  7. Neuroprotective effects of a sesquiterpene lactone and flavanones from Paulownia tomentosa Steud. against glutamate-induced neurotoxicity in primary cultured rat cortical cells.

    Science.gov (United States)

    Kim, Soo-Ki; Cho, Sang-Buem; Moon, Hyung-In

    2010-12-01

    The neuroprotective effects of Paulownia tomentosa against glutamate-induced neurotoxicity were studied in primary cultured rat cortical cells. It was found that the aqueous extract of this medicinal plant significantly attenuated glutamate-induced toxicity. In order to clarify the mechanism(s) underlying this neuroprotective effect, the active fractions and components were isolated and identified. Five compounds were isolated as the methanol extracts from air-dried flowers of P. tomentosa. Isoatriplicolide tiglate exhibited significant neuroprotective activity against glutamate-induced toxicity at concentrations ranging from 1 μM to 10 μM, and exhibited cell viability of approximately 43-78%. Therefore, the neuroprotective effect of P. tomentosa might be due to the inhibition of glutamate-induced toxicity by the sesquiterpene lactone derivative it contains.

  8. Therapeutic time window of flurbiprofen axetil's neuroprotective effect in a rat model of transient focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background The neuroprotective effect of the cyclooxygenase (COX) inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil (FA, COX inhibitor) and its therapeutic time window in a model of transient middle cerebral artery occlusion (MCAO) in rats. Methods Forty-eight male SD rats were randomly assigned into six groups (n=8 in each group); three FA groups, vehicle, sham and ischemia/reperfusion (I/R) groups. Three doses of FA (5, 10 or 20 mg/kg, intravenous infusion) were administered just after cerebral ischemia/reperfusion (I/R). The degree of neurological outcome was measured by the neurologic deficit score (NDS) at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage (MBIVP) was determined with 2,3,5-triphenyltetrazolium chloride (TTC) staining at 72 hours after I/R. In three other groups (n=8 in each group), the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R. Results The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12-24 hours after ischemia reperfusion. Conclusion COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12--24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.

  9. Extract of Antrodia camphorata Exerts Neuroprotection against Embolic Stroke in Rats without Causing the Risk of Hemorrhagic Incidence

    Directory of Open Access Journals (Sweden)

    Ye-Ming Lee

    2014-01-01

    Full Text Available In this study, the neuroprotective effect of an extract of Antrodia camphorata (A. camphorata, a fungus commonly used in Chinese folk medicine for treatment of viral hepatitis and cancer, alone or in combination with aspirin was investigated in a rat embolic stroke model. An ischemic stroke was induced in rats by a selective occlusion of the middle cerebral artery (MCA with whole blood clots and then orally treated with A. camphorata (0.25 and 0.75 g/kg/day alone and combined with aspirin (5 mg/kg/day. Sixty days later, the brains were removed, sectioned, and stained with triphenyltetrazolium chloride and analysed by a commercial image processing software program. Brain infarct volume, neurobehavioral score, cerebral blood perfusion, and subarachnoid and intracerebral hemorrhage incidence were perceived. In addition, potential bleeding side effect of the combinative therapy was assessed by measuring hemoglobin (Hb content during intracerebral hemorrhage and gastric bleeding, prothrombin time (PT, and occlusion time (OT after oral administration. Posttreatment with high dose A. camphorata significantly reduced infarct volume and improved neurobehavioral score (P < 0.05. Since A. camphorata alone or with aspirin did not alter the Hb level, this treatment is safe and does not cause hemorrhagic incident. Remarkably, the combination of A. camphorata and aspirin did not show a significant effect on the bleeding time, PT and OT increase suggesting that A. camphorata may have the neuroprotective effect without the prolongation of bleeding time or coagulation time. From these observations, we suggest that combinative therapy of A. camphorata and aspirin might offer enhanced neuroprotective efficacies without increasing side effects.

  10. Down regulation of cyclooxygenase-2 is involved in delayed neuroprotec-tion by ischemic preconditioning in rats

    Institute of Scientific and Technical Information of China (English)

    Liang XIAO; Fei-li ZHAO; Xing-zu ZHU

    2005-01-01

    Aim: To examine whether the prostaglandins (PGs) pathway is involved in triggering delayed neuroprotection by ischemic preconditioning (IPC) and evaluate the effects of IPC on cyclooxygenase-2 (COX-2) expression following focal cerebral ischemia and reperfusion in rats. Methods: IPC was induced by 10 min of saline infusion into the left internal carotid artery with the right common carotid artery clamped at the same time. Middle cerebral artery occlusion (MCAO) and reperfusion model was produced using intraluminal filament method. Results: IPC 48 h prior to MCAO significantly reduced infarct area as compared with MCAO alone. A nonselective inhibitor of COX indomethacin (3 mg/kg ip) applied 1 h prior to or 1 h after IPC failed to affect its protective effects. IPC had no direct effect on the cortex COX-2 mRNA and protein expression 72 h later, but decreased the expres sion of COX-2 mRNA and protein following ischemia and reperfusion insult. Conclusion: PGs pathways was not involved in triggering delayed neuroprotection by IPC, and IPC induced down-regulation of COX-2 following focal cerebral ischemia and reperfusion in rats in vivo.

  11. Neuroprotective effect of sodium ferulate on transient focal cerebral ischemia by weakening activation of postsynaptic density-95 in rats

    Institute of Scientific and Technical Information of China (English)

    WANG Qiang; CHEN Shao-yang; XIONG Li-ze; JIN Wei-lin; YANG Jing

    2005-01-01

    Objective: To investigate the effects of sodium ferulate (SF), an intravenous drug made from traditional Chinese herbs, on activation of postsynaptic density-95 (PSD-95) and neuroprotection after transient cerebral artery occlusion in rats. Methods: Forty-six male Sprague-Dawley rats were randomized into 2 groups (n=23 in each group): the control group and the SF group. After anesthesia, the middle cerebral artery occlusion (MCAO) was conducted with the intraluminal filament technique. The neurological deficit was assessed with the method devised by Bederson et al.8 The 2, 3, 4-triphenyltetrazolium chloride staining was used to assess the infarct volume. We adopted a modified six-point scale to conduct neurobehavioral evaluation. Immediately the activation of postsynaptic density-95 (PSD-95) was studied with Western blot analysis system in the cortex and striatum of rat brain. Results: The neurologic deficit score of the SF group decreased substantially compared with that of the control group (P<0.05). The infarct volume of the control group (168.1 mm3 ± 42.2 mm3) was significantly larger than that of the SF group (61.5 mm3 ± 28.7 mm3) at 24 hours after reperfusion (P<0.01). And the rats showed some neurological deficit. The activity of PSD-95 in the SF group at most timepoints was less than that in the control group. No upregulation of PSD-95 protein could be detected in the contralateral cortex.Conclusions: Sodium ferulate can induce a neuroprotective effect against the transient focal cerebral ischemic injury and weaken the activation of PSD-95 in ischemic area after MCAO.

  12. 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.

  13. Neuroprotective mechanism of Lycium barbarum polysaccharides against hippocampal-dependent spatial memory deficits in a rat model of obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Chun-Sing Lam

    Full Text Available Chronic intermittent hypoxia (CIH is a hallmark of obstructive sleep apnea (OSA, which induces hippocampal injuries mediated by oxidative stress. This study aims to examine the neuroprotective mechanism of Lycium barbarum polysaccharides (LBP against CIH-induced spatial memory deficits. Adult Sprague-Dawley rats were exposed to hypoxic treatment resembling a severe OSA condition for a week. The animals were orally fed with LBP solution (1 mg/kg daily 2 hours prior to hypoxia or in air for the control. The effect of LBP on the spatial memory and levels of oxidative stress, inflammation, endoplasmic reticulum (ER stress, apoptosis and neurogenesis in the hippocampus was examined. There was a significant deficit in the spatial memory and an elevated level of malondialdehyde with a decreased expression of antioxidant enzymes (SOD, GPx-1 in the hypoxic group when compared with the normoxic control. In addition, redox-sensitive nuclear factor kappa B (NFКB canonical pathway was activated with a translocation of NFКB members (p65, p50 and increased expression levels of NFКB-dependent inflammatory cytokines and mediator (TNFα, IL-1β, COX-2; also, a significantly elevated level of ER stress (GRP78/Bip, PERK, CHOP and autophagic flux in the hypoxic group, leading to neuronal apoptosis in hippocampal subfields (DG, CA1, CA3. Remarkably, LBP administration normalized the elevated level of oxidative stress, neuroinflammation, ER stress, autophagic flux and apoptosis induced by hypoxia. Moreover, LBP significantly mitigated both the caspase-dependent intrinsic (Bax, Bcl2, cytochrome C, cleaved caspase-3 and extrinsic (FADD, cleaved caspase-8, Bid signaling apoptotic cascades. Furthermore, LBP administration prevented the spatial memory deficit and enhanced the hippocampal neurogenesis induced by hypoxia. Our results suggest that LBP is neuroprotective against CIH-induced hippocampal-dependent spatial memory deficits by promoting hippocampal neurogenesis

  14. Differences in the Neuroprotective Effect of Orally Administered Virgin Olive Oil (Olea europaea) Polyphenols Tyrosol and Hydroxytyrosol in Rats.

    Science.gov (United States)

    De La Cruz, José Pedro; Ruiz-Moreno, Maria Isabel; Guerrero, Ana; Reyes, José Julio; Benitez-Guerrero, Adela; Espartero, José Luis; González-Correa, José Antonio

    2015-07-01

    The neuroprotective effect of virgin olive oil (VOO) polyphenols has been related to their antioxidant effect. The main objective was to analyze how tyrosol and hydroxytyrosol contribute to the antioxidant and neuroprotective effects of VOO in a model of hypoxia-reoxygenation in rat brain slices. Rats were treated per os (po) (10 or 20 mg/kg/day) with hydroxytyrosol ethyl ether (HTEE), tyrosol ethyl ether (TEE), or 3,4-di-o-methylidene-hydroxytyrosol ethyl ether (MHTEE), used as a negative control for antioxidant effects. Lipid peroxidation was inhibited with HTEE, TEE, and MHTEE (from 5.0 ± 1.5 to 2.6 ± 1.5, 4.5 ± 1.5, and 4.8 ± 1.5 nmol/mg protein, respectively). However, all three compounds had similar neuroprotective effects: from 2.8 ± 0.07 to 1.8 ± 0.02 arbitrary units for HTEE, 1.4 ± 0.09 arbitrary units for TEE, and 1.3 ± 0.2 arbitrary units for MHTEE. All three compounds inhibited 3-nitrotyrosine production (from 3.7 ± 0.3 to 1.2 ± 0.03 nmol/0.1 g tissue for HTEE, 1.0 ± 0.2 nmol/0.1 g tissue for TEE, and 1.3 ± 0.1 nmol/0.1 g tissue for MHTEE), prostaglandin E2 production (from 55.7 ± 2.2 to 46.4 ± 1.9 pg/0.1 g tissue for HTEE, 24.7 ± 1.3 pg/0.1 g tissue for TEE, and 27.6 ± 2.6 pg/0.1 g tissue for MHTEE), whereas only HTEE inhibited IL1β production (from 35.7 ± 1.5 to 21.6 ± 0.8 pg/0.1 g tissue). Pearson correlation coefficients related neuroprotective effect with an antioxidant effect for HTEE (R = 0.72, p < 0.001), and inhibition of nitrosative stress (R = 0.78, 0.67, and 0.66 for HTEE, TEE, and MHTEE, respectively, p < 0.001) and inflammatory mediators (R = 0.72, 0.79, and 0.64 for HTEE, TEE, and MHTEE, respectively, p < 0.001) with all three compounds.

  15. Neuroprotective effects of intravenous transplantation of bone marrow mononuclear cells from 5-fluorouracil pre-treated rats on ischemic stroke.

    Science.gov (United States)

    Li, Y; Mao, W W; Zhang, C G; Wan, L; Jing, C H; Hua, X M; Li, S T; Cheng, J

    2016-03-15

    Our previous findings showed bone marrow mononuclear cells (BMMNCs) from 5- fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats. This study was undertaken to explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in middle cerebral artery occlusion (MCAO) rat model. Rats were intravenously pre-treated with 5-FU and BMRMNCs were collected at different time points. The contents of growth factors in the supernatant and CXCR4 expression were detected by ELISA and flow cytometry, respectively. MCAO was introduced to rats, and BMMNCs and BMRMNCs collected at 7 days after 5-FU pre-treatment were independently transplanted via the tail vein 24h later. The neurological function was evaluated before cell transplantation and at 24h, 7d and 14d after cell transplantation. Rats were sacrificed at 14d after cell transplantation, the brains were collected for TTC staining, infarct volume detection, NISSL staining, counting of viable cells in the CA1 region, and observation of transplanted cells. BMRMNCs had elevated expressions of growth factors as well as CXCR4 expression. Our results confirmed the better therapeutic effects of BMRMNCs in MCAO rats, demonstrated by reduction in infarct volume, improvement of neurological function and more viable cells in the hippocampus. In addition, more transplanted cells were found after BMRMNCs transplantation at 7 days and 14 days although there was no marked difference at 14 days. These findings indicate that BMRMNCs transplantation may protect ischemic stroke, at least partially, via increasing the secretion of growth factors and migration to the injured site.

  16. Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2003-01-01

    Some anticonvulsants show neuroprotective effects, and may be of use in reducing neuronal death resulting from stroke or traumatic brain injury. Here I report that a broad range of anticonvulsants protect cells in hippocampal slice cultures from death induced by oxygen/glucose deprivation (OGD...

  17. Neuroprotection Against NMDA Induced Cell Death in Rat Nucleus Basalis by Ca2+ Antagonist Nimodipine, Influence of Aging and Developmental Drug Treatment

    NARCIS (Netherlands)

    Luiten, P.G.M.; Douma, B.R.K.; Zee, E.A. van der; Nyakas, C.

    1995-01-01

    In the current study the neuroprotective effect of the L-type calcium channel antagonist nimodipine in rat brain was investigated in N-methyl-D-aspartate-induced neuronal degeneration in vivo. In the present model NMDA was unilaterally injected in the magnocellular nucleus basalis and the neurotoxic

  18. Neuroprotection by the cannabinoid agonist WIN-55212 in an in vivo newborn rat model of acute severe asphyxia.

    Science.gov (United States)

    Martínez-Orgado, José; Fernández-Frutos, Beatriz; González, Rita; Romero, Eva; Urigüen, Leire; Romero, Julián; Viveros, M Paz

    2003-06-10

    This study was designed to evaluate the neuroprotective effect of the cannabinoid agonist WIN-55212 after inducing acute severe asphyxia in newborn rats. The left common carotid artery was ligated in anaesthetised 7-day-old Wistar rats, which were then asphyxiated by inhaling 100% nitrogen for 10 min. Pups recovering from asphyxia were s.c. administered vehicle (n=23), WIN-55212 (0.1 mg/kg, n=18), or WIN-55212 plus the CB1 receptor antagonist SR141716 (3 mg/kg, n=10). Pups undergoing a sham operation served as controls (n=12). Coronal sections of the brain were obtained on the 14th day after surgery and observed under light microscope after Nissl or Fluoro-Jade B (FJB) staining, to respectively quantify surviving or degenerating neurones in the CA1 area of the hippocampus and parietal cortex. Acute asphyxia led to early neurone loss amounting to 19% in the hippocampus and 29% in the cortex (both ANOVA P<0.05 vs. control). Delayed neurone loss occurred in the proportions 13% in the hippocampus and 20% in the cortex (both ANOVA P<0.05 vs. control). Neuronal loss was fully prevented by WIN-55212 administration. Co-administration of SR141716 failed to modify the protective effect of WIN-55212 on early neuronal death, but abolished the WIN-55212-induced prevention of delayed neuronal death. We conclude that when administered after acute severe asphyxia in newborn rats, WIN-55212 shows a neuroprotective effect, reducing both early and delayed neurone loss. This effect is achieved through two parallel CB1-dependent and -independent mechanisms.

  19. The neuroprotective effects of preconditioning exercise on brain damage and neurotrophic factors after focal brain ischemia in rats.

    Science.gov (United States)

    Otsuka, Shotaro; Sakakima, Harutoshi; Sumizono, Megumi; Takada, Seiya; Terashi, Takuto; Yoshida, Yoshihiro

    2016-04-15

    Preconditioning exercise can exert neuroprotective effects after stroke. However, the mechanism underlying these neuroprotective effects by preconditioning exercise remains unclear. We investigated the neuroprotective effects of preconditioning exercise on brain damage and the expression levels of the midkine (MK) and brain-derived neurotrophic factor (BDNF) after brain ischemia. Animals were assigned to one of 4 groups: exercise and ischemia (Ex), no exercise and ischemia (No-Ex), exercise and no ischemia (Ex-only), and no exercise and intact (Control). Rats ran on a treadmill for 30 min once a day at a speed of 25 m/min for 5 days a week for 3 weeks. After the exercise program, stroke was induced by a 60 min left middle cerebral artery occlusion using an intraluminal filament. The infarct volume, motor function, neurological deficits, and the cellular expressions levels of MK, BDNF, GFAP, PECAM-1, caspase 3, and nitrotyrosine (NT) were evaluated 48 h after the induction of ischemia. The infarct volume, neurological deficits and motor function in the Ex group were significantly improved compared to that of the No-Ex group. The expression levels of MK, BDNF, GFAP, and PECAM-1 were enhanced in the Ex group compared to the expression levels in the No-Ex group after brain ischemia, while the expression levels of activated caspase 3 and NT were reduced in the area surrounding the necrotic lesion. Our findings suggest that preconditioning exercise reduced the infract volume and ameliorated motor function, enhanced expression levels of MK and BDNF, increased astrocyte proliferation, increased angiogenesis, and reduced neuronal apoptosis and oxidative stress.

  20. Histological studies of neuroprotective effects of Curcuma longa Linn. on neuronal loss induced by dexamethasone treatment in the rat hippocampus.

    Science.gov (United States)

    Issuriya, Acharaporn; Kumarnsit, Ekkasit; Wattanapiromsakul, Chatchai; Vongvatcharanon, Uraporn

    2014-10-01

    Long term exposure to dexamethasone (Dx) is associated with brain damage especially in the hippocampus via the oxidative stress pathway. Previously, an ethanolic extract from Curcuma longa Linn. (CL) containing the curcumin constituent has been reported to produce antioxidant effects. However, its neuroprotective property on brain histology has remained unexplored. This study has examined the effects of a CL extract on the densities of cresyl violet positive neurons and glial fibrillary acidic protein immunoreactive (GFAP-ir) astrocytes in the hippocampus of Dx treated male rats. It showed that 21 days of Dx treatment (0.5mg/kg, i.p. once daily) significantly reduced the densities of cresyl violet positive neurons in the sub-areas CA1, CA3 and the dentate gyrus, but not in the CA2 area. However, CL pretreatment (100mg/kg, p.o.) was found to significantly restore neuronal densities in the CA1 and dentate gyrus. In addition, Dx treatment also significantly decreased the densities of the GFAP-ir astrocytes in the sub-areas CA1, CA3 and the dentate gyrus. However, CL pretreatment (100mg/kg, p.o.) failed to protect the loss of astrocytes in these sub-areas. These findings confirm the neuroprotective effects of the CL extract and indicate that the cause of astrocyte loss might be partially reduced by a non-oxidative mechanism. Moreover, the detection of neuronal and glial densities was suitable method to study brain damage and the effects of treatment.

  1. Post-hypoxic and ischemic neuroprotection of BMP-7 in the cerebral cortex and caudate-putamen tissue of rat.

    Science.gov (United States)

    Luan, Liju; Yang, Xiaomei; Zhou, Changman; Wang, Ke; Qin, Lihua

    2015-03-01

    Previous reports have indicated that exogenous bone morphogenetic protein-7 (BMP-7) has a neuroprotective effect after cerebral ischemia injury and promotes motor function recovery, but the appropriate BMP-7 concentration and time course are unclear. Here, we assessed endogenous BMP-7 expression in hypoxia and ischemia-damaged brain tissues and investigated the effects of different BMP-7 concentrations in pre- and post-hypoxic primary rat neurons. The results showed that BMP-7 expression was significantly higher in the ischemic hemisphere. The expressions of BMP-7 and caspase-3 were localized in the cytoplasm of the primary cerebral cortical and caudate-putamen neurons 24h after hypoxia/reoxygenation. After BMP-7 treatment, the number of caspase-3 positive neurons began to decrease with increasing BMP-7 concentrations up to 80ng/ml, but not beyond. Although the numbers of caspase-3-positive neurons between pre- and post-hypoxia/reoxygenation were not significantly different, more dendrites were observed in the groups treated prior to hypoxia/reoxygenation. These results suggest that increased BMP-7 expression can be induced in the cerebral cortex and caudate-putamen both in vivo and in vitro in hypoxic-ischemic states. The neuroprotective mechanism of BMP-7 may include apoptosis suppression, and its effect was enhanced from 40 to 80ng/ml. Pre-hypoxic BMP-7 treatment may be useful to stimulate dendrite sprouting in non-injured neurons.

  2. Improvement in regional CBF by L-serine contributes to its neuroprotective effect in rats after focal cerebral ischemia.

    Directory of Open Access Journals (Sweden)

    Tao-Jie Ren

    Full Text Available To investigate the mechanisms underlying the neuroprotective effect of L-serine, permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery while monitoring cerebral blood flow (CBF. Rats were divided into control and L-serine-treated groups after middle cerebral artery occlusion. The neurological deficit score and brain infarct volume were assessed. Nissl staining was used to quantify the cortical injury. L-serine and D-serine levels in the ischemic cortex were analyzed with high performance liquid chromatography. We found that L-serine treatment: 1 reduced the neurological deficit score, infarct volume and cortical neuron loss in a dose-dependent manner; 2 improved CBF in the cortex, and this effect was inhibited in the presence of apamin plus charybdotoxin while the alleviation of both neurological deficit score and infarct volume was blocked; and 3 increased the amount of L-serine and D-serine in the cortex, and inhibition of the conversion of L-serine into D-serine by aminooxyacetic acid did not affect the reduction of neurological deficit score and infarct volume by L-serine. In conclusion, improvement in regional CBF by L-serine may contribute to its neuroprotective effect on the ischemic brain, potentially through vasodilation which is mediated by the small- and intermediate-conductance Ca(2+-activated K(+ channels on the cerebral blood vessel endothelium.

  3. Neuroprotective activity of parawixin 10, a compound isolated from Parawixia bistriata spider venom (Araneidae: Araneae in rats undergoing intrahippocampal NMDA microinjection

    Directory of Open Access Journals (Sweden)

    Helene Aparecida Fachim

    2015-01-01

    Full Text Available Background: Parawixia bistriata is a semi colonial spider found mainly in southeastern of Brazil. Parawixin 10 (Pwx 10 a compound isolated from this spider venom has been demonstrated to act as neuroprotective in models of injury regulating the glutamatergic neurotransmission through glutamate transporters. Objectives: The aim of this work was to evaluate the neuroprotective effect of Pwx 10 in a rat model of excitotoxic brain injury by N methyl D aspartate (NMDA injection. Material and Methods: Male Wistar rats have been used, submitted to stereotaxic surgery for saline or NMDA microinjection into dorsal hippocampus. Two groups of animals were treated with Pwx 10. These treated groups received a daily injection of the Pwx 10 (2.5 mg/μL in the right lateral ventricle into rats pretreated with NMDA, always at the same time, each one starting the treatment 1 h or 24 h. Nissl staining was performed for evaluating the extension and efficacy of the NMDA injury and the neuroprotective effect of Pwx 10. Results: The treatment with Pwx 10 showed neuroprotective effect, being most pronounced when the compound was administrated from 1 h after NMDA in all hippocampal subfields analyzed (CA1, CA3 and hilus. Conclusion: These results indicated that Pwx 10 may be a good template to develop therapeutic drugs for treating neurodegenerative diseases, reinforcing the importance of continuing studies on its effects in the central nervous system.

  4. Neuroprotective Effects of Sulphated Agaran from Marine Alga Gracilaria cornea in Rat 6-Hydroxydopamine Parkinson's Disease Model: Behavioural, Neurochemical and Transcriptional Alterations.

    Science.gov (United States)

    Souza, Ricardo Basto; Frota, Annyta Fernandes; Sousa, Rayane Siqueira; Cezario, Nayara Araújo; Santos, Tarcizio Brito; Souza, Luziana Mara Frota; Coura, Chistiane Oliveira; Monteiro, Valdécio Silvano; Cristino Filho, Gerardo; Vasconcelos, Silvânia Maria Mendes; da Cunha, Rodrigo Maranguape Silva; Aguiar, Lissiana Magna Vasconcelos; Benevides, Norma Maria Barros

    2017-02-01

    Parkinson's disease (PD) is a multifactorial disease associated with the degeneration of dopaminergic neurons and behavioural alterations. Natural bioactive compounds may provide new therapeutic alternatives for neurodegenerative disorders, such as PD. The sulphated polysaccharides isolated from marine algae are heterogenic molecules that show different biological activities. The red marine alga Gracilaria cornea has a sulphated polysaccharide (SA-Gc) with structure and anti-inflammatory and antinociceptive activities reported in the literature. Therefore, this study aimed to evaluate the neuroprotective effects of SA-Gc in rat model PD induced by 6-hydroxydopamine (6-OHDA). Firstly, we established the PD model in rats, induced by an intrastriatal injection (int.) of 6-OHDA, followed by a single administration of SA-Gc (15, 30 or 60 μg; int.). On the 14th day, behavioural tests were performed. After killing, brain areas were dissected and used for neurochemical and/or transcriptional analyses. The results showed that SA-Gc (60 μg, int.) promoted neuroprotective effects in vivo through reducing the oxidative/nitroactive stress and through alterations in the monoamine contents induced by 6-OHDA. Furthermore, SA-Gc modulated the transcription of neuroprotective and inflammatory genes, as well as returning behavioural activities and weight gain to normal conditions. Thus, this study reports the neuroprotective effects of SA-Gc against 6-OHDA in rats.

  5. Pre, intra and post-ischemic hypothermic neuroprotection in temporary focal cerebral ischemia in rats: morphometric analysis

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    Roberto Alexandre Dezena

    2012-08-01

    Full Text Available OBJECTIVE: To evaluate the neuroprotection of mild hypothermia, applied in different moments, in temporary focal cerebral ischemia in rats. METHODS: Rats was divided into Control (C, Sham (S, Ischemic-control(IC, Pre-ischemic Hypothermia (IH1, Intra-ischemic Hypothermia (IH2, and Post-ischemic Hypothermia (IH3 groups. Morphometry was performed using the KS400 software (Carl Zeiss® in coronal sections stained by Luxol Fast Blue. Ischemic areas and volumes were obtained. RESULTS: Statistically, blue areas showed difference for C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.01; p=0.03, and no difference between C vs. S, IC vs. IH3 and IH vs. IH2 (p=0.39; p=0.85; p=0.63. Red areas showed difference between C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.009; p=0.03, and no difference between C vs. S, IC vs. IH3 and IH1 vs. IH2 (p=0.48; p=0.27; p=0.68. Average ischemic areas and ischemic volumes showed difference between IC vs. IH1 and IC vs. IH2 (p=0.0001 and p=0.0011, and no difference between IC vs. IH3 and IH1 vs. IH2 (p=0.57; p=0.79. CONCLUSION: Pre-ischemic and intra-ischemic hypothermia were shown to be similarly neuroprotective, but this was not true for post-ischemic hypothermia.

  6. Neuroprotective Effects of a Smoothened Receptor Agonist against Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats

    Science.gov (United States)

    Hu, Quan; Li, Tong; Wang, Lingxiao; Xie, Yunkai; Liu, Song; Bai, Xuemei; Zhang, Tiantian; Bo, Shishi; Xin, Danqing; Xue, Hao; Li, Gang; Wang, Zhen

    2017-01-01

    The sonic hedgehog (Shh) signaling pathway plays a fundamental role in the central nervous system (CNS) development, but its effects on neural cell survival and brain repair after subarachnoid hemorrhage (SAH) has not been well-investigated. The present study was undertaken to evaluate the influence of an agonist of the Shh co-receptor Smoothened (Smo), purmorphamine (PUR), on early brain injury (EBI) as well as the underlying mechanisms after SAH. PUR was administered via an intraperitoneal injection with a dose of 0.5, 1, and 5 mg/kg at 2, 6, 24, and 46 h after SAH in rat model. The results showed that PUR treatment significantly ameliorated brain edema, improved neurobehavioral function, and attenuated neuronal cell death in the prefrontal cortex (PFC), associated with a decrease in Bax/Bcl-2 ratio and suppression of caspase-3 activation at 48 h after SAH. PUR also promoted phospho-ERK levels. Additionally, PUR treatment markedly decreased MDA concentration accompanied with the elevation in the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in PFC. Notably, PUR treatment significantly reversed the changes of Shh pathway mediators containing Patched, Gli1, and Shh by SAH insult, and the neuroprotection of PUR on SAH was blocked by Smo antagonist cyclopamine. These results indicated that PUR exerts neuroprotection against SAH-evoked injury in rats, mediated in part by anti-apoptotic and anti-oxidant mechanism, up-regulating phospho-ERK levels, mediating Shh signaling molecules in the PFC. PMID:28149272

  7. Boswellic Acid Improves Cognitive Function in a Rat Model Through Its Antioxidant Activity - Neuroprotective effect of Boswellic acid -

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    Saeedeh Ebrahimpour

    2017-03-01

    Full Text Available Objectives: Boswellic acid (BA, a compound isolated from the gum-resin of Boswellia carterii, is a pentacyclic terpenoid that is active against many inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn's disease, and memory impairment, but the mechanism is poorly understood. This study investigated the effects of boswellic acid on spatial learning and memory impairment induced by trimethyltin (TMT in Wistar rats. Methods: Forty male Wistar rats were randomly divided into 5 groups: Normal group, TMT-administrated rats (8.0 mg/kg, Intraperitoneally, i.p. and TMT + BA (40, 80 and 160 mg/kg, i.p.-administrated rats. BA was used daily for 21 days. To evaluate the cognitive improving of BA, we performed the Morris water maze test. Moreover, to investigate the neuroprotective effect of BA, we determined the acetylcholinesterase (AchE activity, the malondialdehyde (MDA level as a marker of lipid peroxidation, and the glutathione (GSH content in the cerebral cortex. Results: Treatment with TMT impaired learning and memory, and treatment with BA at a dose of 160 mg/kg produced a significant improvement in learning and memory abilities in the water maze tasks. Consistent with behavioral data, the activity of AChE was significantly increased in the TMT-injected rats compared to the control group (P < 0.01 whereas all groups treated with BA presented a more significant inhibitory effect against AChE than the TMT-injected animals. In addition, TMT reduced the GSH content and increased the MDA level in the cerebral cortex as compared to the control group P < 0.01. On the other hand, treatment with BA at 160 mg/kg slightly increased the GSH content and reduced the MDA level in comparison to the TMT-administered group (P < 0.01. Conclusion: The above results suggest that the effect of BA in improving the cognitive function may be mediated through its antioxidant activity.

  8. Flurbiprofen axetil promotes neuroprotection by activation of cerebral peroxisome proliferator-activated receptor gamma after focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    LIU Jun-le; JIN Jian-wen; PEI Shu-jun; WANG Chen

    2012-01-01

    Background Our previous papers indicate that flurbiprofen axetil (FA),a cyclooxygenase inhibitor,is a promising therapeutic strategy for cerebral ischemia in rats.This study aimed to investigate whether FA could promote a neuroprotective effect by activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) after focal cerebral ischemia in rats.Methods Totally 48 male Sprague-Dawley (SD) rats were randomly assigned into six groups (n=8 in each group):animals in group ischemia/reperfusion (I/R) only received 120-minute transient middle cerebral artery occlusion (tMCAO);animals in group I/R +FA were administered FA (10 mg/kg) by caudal vein just after 120-minute tMCAO; animals in group I/R +FA+GW9662 were administered GW9662 (a PPAR-γ inhibitor,1 mg/kg) intraperitoneally 30 minutes before cerebral ischemia onset and FA (10 mg/kg) by caudal vein just after 120-minute tMCAO; animals in group I/R +GW9662 were administered GW9662 (1 mg/kg) intraperitoneally 30 minutes before cerebral ischemia onset; animals in group I/R +DMSO were administered 3% DMSO (vehicle of GW9662,1 ml/kg) intraperitoneally 30 minutes before cerebral ischemia onset; animals in sham group experienced the identical surgery apart from the insertion of the nylon filament.The neurologic deficit score (NDS) were performed at 72 hours after reperfusion,and then mean brain infarct volume percentage (MBIVP) was determined with 2,3,5-triphenyltetrazolium chloride (TTC) 10(g)/L staining.Results NDS was significantly increased in group I/R+FA (12.0 (10.0-15.0)),group I/R+FA+GW9662 (10.0 (8.0-12.0)),and in group I/R+FA+DMSO (12.0 (9.0-14.0)) at 72 hours after reperfusion compared with those in group I/R (7.5(6.0-10.0)) NDS was conspicuously different between group I/R+FA (12.0 (10.0-15.0)) and group I/R+FA+GW9662 (10.0 (8.0-12.0)).MBIVP in group I/R ((45.82±8.83)%) was significantly greater than that in group I/R+FA((23.52±9.90)%),group I/R+FA+GW9662 ((33.17±7.15)%); MBIVP in group

  9. A comparison of neuroprotective efficacy of newly developed oximes (K203, K206) and commonly used oximes (obidoxime, HI-6) in tabun-poisoned rats.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana; Vasina, Libor; Bajgar, Jiri; Kuca, Kamil; Musilek, Kamil

    2009-01-01

    The neuroprotective effects of newly developed oximes (K203, K206) and commonly used oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with tabun at a sublethal dose (180 microg/kg i.m.; 80% LD(50)) were studied. The tabun-induced neurotoxicity was monitored by using a functional observational battery and an automatic measurement of motor activity. The neurotoxicity of tabun was monitored at 24 hours and 7 days following tabun challenge. The results indicate that K203 and obidoxime in combination with atropine allow all tabun-poisoned rats to survive within 7 days following tabun challenge, while 2 nontreated tabun-poisoned rats and 1 tabun-poisoned rat treated with K206 or HI-6 in combination with atropine died within 7 days. Only one of the newly developed oximes (K203) combined with atropine seems to be effective for a decrease in tabun-induced neurotoxicity within 24 hours after tabun sublethal poisoning, although it is not able to eliminate tabun-induced neurotoxicity completely. On the other hand, the neuroprotective efficacy of commonly used oximes (obidoxime and HI-6), as well as one of the new synthesized oximes (K206), is significantly lower in comparison with K203, according to the number of eliminated tabun-induced neurotoxic signs at 24 hours after tabun challenge. Due to its neuroprotective effects, K203 appears to be a suitable oxime for the antidotal treatment of acute tabun poisonings.

  10. Electroacupuncture-Induced Neuroprotection against Cerebral Ischemia in Rats: Role of the Dopamine D2 Receptor

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    Ming-Shu Xu

    2013-01-01

    Full Text Available Background. Cerebral ischemia is known to produce brain damage and related behavioural deficits, including memory deficits and motor disorders. Evidence shows that EA significantly promotes recovery of neurological function and thus improves quality of life. Objective. Evidence exists for the involvement of catecholamines in human neuroplasticity. A better understanding of dopaminergic (DAergic modulation in this process will be important. Methods. A total of 72 adult male Sprague-Dawley (SD rats were divided into 6 groups: normal, model, EA, spiperone group, EA + spiperone group, and pergolide. The middle cerebral artery occlusion (MCAO model was used in all 6 groups except the normal group. A behavioural assessment was conducted at 1, 3, 5, and 7 days after MCAO. The percent of brain infarct area was also determined 7 days after MCAO. Tyrosine hydroxylase (TH and growth-associated protein 43 (GAP-43 fluorescence double labeling was performed in the striatum. Results. In this study, we found that EA at Fengchi (GB20 acupoints resulted in marked improvements based on a behavioural assessment. Both TTC staining and GAP-43 immunofluorescence labeling results showed that EA treatment reduced ischemia injury and promoted neuroplasticity compared with the model group. The D2R-selective agonist, pergolide, showed similar results, but these results were reversed by the D2R-selective antagonist, spiperone. We also found that there were more colocalization and expression of GAP-43 and TH in the EA and pergolide groups than those in the other groups. Conclusion. These results suggest that the neuroplasticity induced by EA was mediated by D2 autoreceptors in DAergic neurons.

  11. Evidence for neuroprotective effects of endogenous brain-derived neurotrophic factor after global forebrain ischemia in rats.

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    Larsson, E; Nanobashvili, A; Kokaia, Z; Lindvall, O

    1999-11-01

    The levels of brain-derived neurotrophic factor (BDNF) vary between different forebrain areas and show region-specific changes after cerebral ischemia. The present study explores the possibility that the levels of endogenous BDNF determine the susceptibility to ischemic neuronal death. To block BDNF activity the authors used the TrkB-Fc fusion protein, which was infused intraventricularly in rats during 1 week before and 1 week after 5 or 30 minutes of global forebrain ischemia. Ischemic damage was quantified in the striatum and hippocampal formation after 1 week of reperfusion using immunocytochemistry and stereological procedures. After the 30-minute insult, there was a significantly lower number of surviving CA4 pyramidal neurons, neuropeptide Y-immunoreactive dentate hilar neurons, and choline acetyltransferase- and TrkA-positive, cholinergic striatal interneurons in the TrkB-Fc-infused rats as compared to controls. In contrast, the TrkB-Fc treatment did not influence survival of CA1 or CA3 pyramidal neurons or striatal projection neurons. Also, after the mild ischemic insult (5 minutes), neuronal death in the CA1 region was similar in the TrkB-Fc-treated and control groups. These results indicate that endogenous BDNF can protect certain neuronal populations against ischemic damage. It is conceivable, though, that efficient neuroprotection after brain insults is dependent not only on this factor but on the concerted action of a large number of neurotrophic molecules.

  12. A comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced memory impairments in rats

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    Talha Jawaid

    2015-01-01

    Full Text Available The comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced neuroinflammation in albino Wistar rats was studied. Male albino rats were administered with scopolamine to induce memory impairment. The standard nootropic agent, piracetam (200 mg/kg b.w., [i.p.], perindopril (0.1 mg/kg b.w., [i.p.], enalapril (0.1 mg/kg b.w., [i.p.], and ramipril (0.1 mg/kg b.w., [i.p.] were administered in different group of animals for 5 days. On 5 th day, scopolamine (1 mg/kg b.w., i.p. was administered after 60 min of the last dose of test drug. Memory function was evaluated in Morris water maze (MWM test and pole climbing test (PCT. Biochemical estimations like glutathione (GSH, malondialdehyde (MDA, and acetylcholinesterase activity in the brain were estimated after completion of behavior study. All three test groups shows improvement in learning and memory in comparison to control group. Perindopril treated group showed a more effective significant decrease in escape latency time and transfer latency time compared to enalapril and ramipril treated group on day 4 in MWM test and PCT, respectively. Perindopril shows a significant reduction in MDA level and acetylcholinesterase activity and a significant rise in GSH level compared to enalapril and ramipril. The finding of this study indicates that Perindopril is more effective in memory retention compared to enalapril and ramipril.

  13. Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

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    Adel Jungling

    2017-02-01

    Full Text Available Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson’s disease (PD. The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

  14. Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

    Science.gov (United States)

    Jungling, Adel; Reglodi, Dora; Karadi, Zsofia Nozomi; Horvath, Gabor; Farkas, Jozsef; Gaszner, Balazs; Tamas, Andrea

    2017-01-01

    Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson’s disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life. PMID:28216584

  15. Effects of Postnatal Enriched Environment in a Model of Parkinson's Disease in Adult Rats.

    Science.gov (United States)

    Jungling, Adel; Reglodi, Dora; Karadi, Zsofia Nozomi; Horvath, Gabor; Farkas, Jozsef; Gaszner, Balazs; Tamas, Andrea

    2017-02-14

    Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson's disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

  16. Novel role for gabapentin in neuroprotection of central nervous system in streptozotocine-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Giyasettin BAYDAS; Ertugrul SONKAYA; Mehmet TUZCU; Abdullah YASAR; Emir DONDER

    2005-01-01

    Aim: To investigate the effect of gabapentin on neural [neuron-specific enolase (NSE)] and glial markers [glial fibrillary acidic protein (GFAP) and S100B] in different brain regions of diabetic rats. Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocine (50 mg/kg body weight). Rats in one group received vehicle only for 6 weeks. The levels of GFAP, S 100B, and NSE were determined by immunoblotting in the hippocampus, cortex, and cerebellum. Lipid peroxidation (LPO as malondialdehyde+ 4-hydroxyalkenals) and glutathione (GSH) levels were also determined in the same brain parts. Results: Total and degraded GFAP content and S100B protein expression in different areas of brain tissues significantly increased in diabetic rats compared to control rats. Similarly, NSE levels were also significantly elevated in hyperglycemic rats. In addition, there was a significant increase in LPO levels in the diabetic rat brain compared to control rat brains. Pretreatment with gabapentin prevented the upregulation of GFAP, S 100B, and NSE in all brain regions of diabetic rats. The level of LPO was reduced, but not completely halted, by treatment with gabapentin. Conclusion: These results suggest that diabetes causes glial and neuronal injury, possibly as a result of elevated oxidative stress, and that gabapentin protects neurons and glial cells. Thus, we predict that gabapentin treatment will attenuate the hippocampal and cortical neurodegeneration observed during diabetes mellitus in rats.

  17. Neuroprotection of GST, an extract of traditional Chinese herb, against ischemic brain injury induced by transient brain ischemia and reperfusion in rat hippocampus.

    Science.gov (United States)

    Sun, Ya-Feng; Pei, Dong-Sheng; Zhang, Qing-Xiu; Zhang, Guang-Yi

    2008-06-01

    In this study, we investigated the effect of GST, an extract of Chinese traditional herb, on transient brain ischemia/reperfusion-induced neuronal cell death. Immunoblotting was used to detect the phosphorylation of MLK, JNK and c-jun. Transient (15 minutes) brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats. GST was administrated to the SD rats 20 minutes before ischemia or 1 hour after ischemia. Our data showed that the pretreatment of GST could inhibit phosphorylation of MLK, JNK and c-jun. Moreover, GST showed potent neuroprotective effects on ischemic brain damage in vivo and administration of it 1 hour after ischemia also achieved the protective effects. These results indicate that GST has a prominent neuroprotection action against brain ischemic damage and provides a promising therapeutic approach for ischemic brain injury.

  18. A comparison of the neuroprotective efficacy of newly developed oximes (K117, K127) and currently available oxime (obidoxime) in tabun-poisoned rats

    OpenAIRE

    Kassa, Jiri; Karasova, Jana Zdarova; Musilek, Kamil; Kuca, Kamil; Jung, Young-Sik

    2009-01-01

    The potency of newly developed bispyridinium compounds (K117, K127) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with currently available oxime (obidoxime) using functional observational battery. The neuroprotective effects of atropine alone and atropine combined with one of three bispyridinium oximes (K117, K127, obidoxime) on rats poisoned with tabun at a sublethal dose (180 μg/kg i.m.; 80% of LD50 value) were studied. Tabun-induced neurotoxicity was monitored us...

  19. A comparison of neuroprotective efficacy of the oxime K203 and its fluorinated analogue (KR-22836) with obidoxime in Tabun-poisoned rats.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Tesarova, Sandra; Musilek, Kamil; Kuca, Kamil; Jung, Young-Sik

    2010-11-01

    The ability of the newly developed bispyridinium compound K203 and its fluorinated analogue KR-22836 to reduce tabun-induced acute neurotoxic signs and symptoms was compared with the currently available reactivator of acetylcholinesterase-obidoxime. Tabun-induced neurotoxicity and the neuroprotective effects of all tested oximes in combination with atropine in rats poisoned with tabun at a sublethal dose (200 μg/kg intramuscularly (i.m.); 80% of LD(50) value) were monitored by a functional observational battery at 24 hr after tabun challenge. The results indicate that all tested oximes combined with atropine were able to survive tabun-poisoned rats 24 hr after tabun challenge while one non-treated tabun-poisoned rat died within 24 hr after tabun poisoning. All tested oximes combined with atropine were able to decrease tabun-induced neurotoxicity in the case of sublethal poisoning but they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. While the ability to reduce tabun-induced acute neurotoxicity of obidoxime and K203 was similar, the neuroprotective efficacy of KR-22836 was slightly higher compared to other tested oximes. Thus, the newly developed fluorinated analogue of K203, called KR-22836, is able to slightly increase the neuroprotective effectiveness of antidotal treatment of acute tabun poisonings compared to K203 and currently available obidoxime.

  20. Sesamin suppresses activation of microglia and p44/42 MAPK pathway, which confers neuroprotection in rat intracerebral hemorrhage.

    Science.gov (United States)

    Ohnishi, M; Monda, A; Takemoto, R; Matsuoka, Y; Kitamura, C; Ohashi, K; Shibuya, H; Inoue, A

    2013-03-01

    Thrombin plays important roles in the pathology of intracerebral hemorrhage (ICH). The recruitment of activated microglia, accompanied by thrombin-induced phosphorylation of the mitogen-activated protein kinase (MAPK) family, contributes to ICH-associated neuron loss. Here we investigated the possibility that sesamin, a lignan of sesame seed oil, is a natural candidate as an inhibitor of microglial activation and MAPK pathways under ICH insults. Sesamin (30-100 μM) suppressed thrombin-induced nitric oxide (NO) production by primary-cultured rat microglia via inhibition of inducible NO synthase (iNOS) protein expression, independently of the antioxidative effect. Sesamin selectively inhibited p44/42 MAPK phosphorylation in the MAPK family (p38 and p44/42) involved in iNOS protein expression in primary-cultured rat microglia. An in vivo rat ICH model was prepared by intrastriatal injection of 0.20U collagenase type IV unilaterally. ICH evoked the phosphorylation of p44/42 MAPK, microglial proliferation with morphological change into the activated ameboid form, and neuron loss. The phosphorylation of p44/42 MAPK was inhibited by intracerebroventricular administration of 30-nmol sesamin. Sesamin prevented ICH-induced increase of microglial cells in the perihematomal area. Notably, ramified microglia, the resting morphology, were observed in brain sections of the animals administrated sesamin. Sesamin furthermore achieved neuroprotection in the perihematomal area but not in the hematomal center. These results suggest that sesamin is a promising natural product as a novel therapeutic strategy based on the regulation of microglial activities accompanied by the activated p44/42 MAPK pathway in ICH.

  1. Neuroprotective effects of salvianolic acid B against oxygen-glucose deprivation/reperfusion damage in primary rat cortical neurons

    Institute of Scientific and Technical Information of China (English)

    WANG Yun; JIANG Yu-feng; HUANG Qi-fu; GE Gui-ling; CUI Wei

    2010-01-01

    Background Cerebral ischemia-reperfusion injury is the main reason for the loss of neurons in the ischemic cerebrovascular disease. Therefore, to deeply understand its pathogenesis and find a new target is the key issue to be solved. This research aimed to investigate the neuroprotective effects of salvianolic acid B (SalB) against oxygen-glucose deprivation/reperfusion (OGD/RP) damage in primary rat cortical neurons.Methods The primary cultures of neonatal Wister rats were randomly divided into the control group, the OGD/RP group and the SalB-treatment group (10 mg/L). The cell model was established by depriving of oxygen and glucose for 3 hours and reperfusion for 3 hours and 24 hours, respectively. The neuron viability was determined by MTT assay. The level of cellular reactive oxygen species (ROS) was detected by fluorescent labeling method and spin trapping technique respectively. The activities of neuronal Mn-superoxide dismutase (Mn-SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) were assayed by chromatometry. The mitochondria membrane potential (△ψm) was quantitatively analyzed by flow cytometry. The release rate of cytochrome c was detected by Western blotting. The neuronal ultrastructure was observed by transmission electron microscopy. Statistical significance was evaluated by analysis of variance (ANOVA)followed by Student-Newman-Keuls test.Results OGD/RP increased the level of cellular ROS, but decreased the cell viability and the activities of Mn-SOD, CAT and GSH-PX; SalB treatment significantly reduced the level of ROS (P <0.05); and enhanced the cell viability (P <0.05)and the activities of these antioxidases (P <0.05). Additionally, OGD/RP induced the fluorescence value of △ψm to diminish and the release rate of cytochrome c to rise notably; SalB markedly elevated the level of △ψm (P <0.01) and depressed the release rate of cytochrome c (P <0.05); it also ameliorated the neuronal morphological injury.Conclusion The

  2. Neuroprotective effects of edaravone on early brain injury in rats after subarachnoid hemorrhage

    Institute of Scientific and Technical Information of China (English)

    GAO Yang; DING Xin-sheng; XU Shu; WANG Wei; ZUO Qi-long; KUAI Feng

    2009-01-01

    Background The underlying mechanism of early neurobiological impairment after subarachnoid hemorrhage (SAH) is not well understood,but the system of reactive oxygen superoxide (ROS) might be involved.Edaravone (MC1-186),a potent free radical scavenger that prevents apoptosis of neurons,was thus used in this study to see its possible therapeutic effect in early brain injury due to SAH in a rat model.Methods One hundred and twenty male Sprague-Dawley rats were randomly assigned to four groups:group 1,control rats receiving sham operation only;group 2,rats with SAH treated by saline;group 3,rats with SAH treated with 1 mg/kg MCI-186 injected intraperitoneally;and group 4,rats with SAH treated with 3 mg/kg MC1-186.Treated with either saline or MC1-186 twice daily for two consecutive days after SAH,the rats were sacrificed for measurements of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and histological analysis of caspase-3 protein by Western blotting and immunohistochemical staining.In addition,mortality and neurological scores were statistically analyzed by the chi-square test and Dunn's procedure respectively for each group.One-way analysis of variance followed by the Tukey's procedure was also used in data analysis.Results The rats in group 2 that received saline only showed neurological impairment as well as elevated mortality,and were found to have significantly increased levels of MDA and caspase-3,but reduced SOD activities in brain tissues (P<0.05).When treated with MC1-186 at two different dosages,the rats in groups 3 and 4 had markedly decreased levels of MDA and caspase-3 but increased SOD activities in the brain tissue (P<0.05),along with improved scores of neurological evaluation (P<0.05).Conclusions This study sheds some lights on the therapy of SAH-induced early brain injury by providing the promising data indicating that MC1-186,a radical scavenger,can efficiently diminish apoptosis of neurons and thus prevent the function

  3. Neuroprotective effect of berberine is mediated by MAPK signaling pathway in experimental diabetic neuropathy in rats.

    Science.gov (United States)

    Zhou, Jiyin; Du, Xiaohuang; Long, Min; Zhang, Zuo; Zhou, Shiwen; Zhou, Jianyun; Qian, Guisheng

    2016-03-05

    The mechanisms leading to diabetic neuropathy are complex. As an active component in several traditional Chinese medicines, berberine has a beneficial effect in the treatment of diabetes with hyperlipidemia. This study evaluated the protective effects of berberine on diabetic neuropathy induced by streptozotocin and a high-carbohydrate/high-fat diet in rats. Diabetic neuropathy was induced in rats by intraperitoneal injection of 35 mg/kg streptozotocin and a high-carbohydrate/high-fat diet. Two weeks after diabetes induction, rats were treated with berberine (100 mg/kg) and rosiglitazone (4 mg/kg) for 24 weeks. Rats were studied using evoked potentials, the Morris water maze, transmission electron microscopy, real-time PCR, and Western blotting. Blood glucose, glycated hemoglobin, lipid profile, body weight, evoked potentials, and memory were altered in diabetic rats, as was the hippocampal expression of neuritin mRNA, p38 mitogen-activated protein kinase mRNA, c-Jun N-terminal kinase (JNK) mRNA, extracellular signal-regulated kinase mRNA and the phospho-proteins of p38, JNK, and extracellular signal-regulated kinase. In diabetic rats, berberine decreased body weight and the blood levels of glucose, glycated hemoglobin, triglyceride, and total cholesterol, improved memory and affected evoked potential by decreasing latency. Berberine decreased the mRNA expression of neuritin, p38, and JNK and the protein expression of neuritin, p-p38, and p-JNK. Slight micropathological changes were observed in the hippocampus of berberine-treated diabetic rats. These findings suggest that berberine has a beneficial effect against diabetic neuropathy by improving micropathology and increasing neuritin expression via the mitogen-activated protein kinase signaling pathway.

  4. Neuroprotective Effect of Gui Zhi (Ramulus Cinnamomi on Ma Huang- (Herb Ephedra- Induced Toxicity in Rats Treated with a Ma Huang-Gui Zhi Herb Pair

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    Fang-hao Zheng

    2015-01-01

    Full Text Available Herb Ephedra (Ma Huang in Chinese and Ramulus Cinnamomi (Gui Zhi in Chinese are traditional Chinese herbs, often used together to treat asthma, nose and lung congestion, and fever with anhidrosis. Due to the adverse effects of ephedrine, clinical use of Ma Huang is restricted. However, Gui Zhi extract has been reported to decrease spontaneous activity in rats and exert anti-inflammatory and neuroprotective effects. The present study explored the possible inhibitory effect of Gui Zhi on Ma Huang-induced neurotoxicity in rats when the two herbs were used in combination. All Ma Huang and Ma Huang-Gui Zhi herb pair extracts were prepared using methods of traditional Chinese medicine and were normalized based on the ephedrine content. Two-month-old male Sprague-Dawley rats (n=6 rats/group were administered Ma Huang or the Ma Huang-Gui Zhi herb pair extracts for 7 days (ephedrine = 48 mg/kg, and locomotor activity was measured. After 7 days, oxidative damage in the prefrontal cortex was measured. Gui Zhi decreased hyperactivity and sensitization produced by repeated Ma Huang administration and attenuated oxidative stress induced by Ma Huang. The results of this study demonstrate the neuroprotective potential of Gui Zhi in Ma Huang-induced hyperactivity and oxidative damage in the prefrontal cortex of rats when used in combination.

  5. Neuroprotective effect of gui zhi (ramulus cinnamomi) on ma huang- (herb ephedra-) induced toxicity in rats treated with a ma huang-gui zhi herb pair.

    Science.gov (United States)

    Zheng, Fang-Hao; Wei, Ping; Huo, Hui-Ling; Xing, Xue-Feng; Chen, Fei-Long; Tan, Xiao-Mei; Luo, Jia-Bo

    2015-01-01

    Herb Ephedra (Ma Huang in Chinese) and Ramulus Cinnamomi (Gui Zhi in Chinese) are traditional Chinese herbs, often used together to treat asthma, nose and lung congestion, and fever with anhidrosis. Due to the adverse effects of ephedrine, clinical use of Ma Huang is restricted. However, Gui Zhi extract has been reported to decrease spontaneous activity in rats and exert anti-inflammatory and neuroprotective effects. The present study explored the possible inhibitory effect of Gui Zhi on Ma Huang-induced neurotoxicity in rats when the two herbs were used in combination. All Ma Huang and Ma Huang-Gui Zhi herb pair extracts were prepared using methods of traditional Chinese medicine and were normalized based on the ephedrine content. Two-month-old male Sprague-Dawley rats (n = 6 rats/group) were administered Ma Huang or the Ma Huang-Gui Zhi herb pair extracts for 7 days (ephedrine = 48 mg/kg), and locomotor activity was measured. After 7 days, oxidative damage in the prefrontal cortex was measured. Gui Zhi decreased hyperactivity and sensitization produced by repeated Ma Huang administration and attenuated oxidative stress induced by Ma Huang. The results of this study demonstrate the neuroprotective potential of Gui Zhi in Ma Huang-induced hyperactivity and oxidative damage in the prefrontal cortex of rats when used in combination.

  6. Evaluation of neuroprotective, anticonvulsant, sedative and anxiolytic activity of citicoline in rats.

    Science.gov (United States)

    Abdolmaleki, Arash; Moghimi, Ali; Ghayour, Mohammad B; Rassouli, Morteza B

    2016-10-15

    Citicoline (cytidine-5'-diphosphocholine) is a neuroprotective agent that is administered following ischemic and traumatic brain injuries. There is little information about the antiseizure and anxiolytic effects of citicoline, which are therefore addressed in the present study. For evaluating the anticonvulsant effect of citicoline in the pentylentetrazole seizure model, a single intraperitoneal dose of citicoline was administered at 50, 100 or 150mg/kg. Sedative and anxiolytic effects of citicoline were examined via elevated plus maze and pentobarbital induced sleep tests. Results show that citicoline at the doses of 100 and 150mg/kg significantly delayed the latent period compared with the control (PCiticoline at the doses of 100 and 150mg/kg significantly decreased total locomotion compared with the control (Pciticoline at the doses of 100 and 150mg/kg significantly increased both percentage of entry and time spent in the open arms in the elevated plus maze test (Pciticoline significantly reduced the latency to sleep (Pciticoline has anticonvulsant activity and sedative effect.

  7. Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteine

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    Gang Chen

    2008-01-01

    Full Text Available Although N-acetylcysteine (NAC has been shown to be neuroprotective for traumatic brain injury (TBI, the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB and inflammatory proteins such as interleukin-1β (IL-1β, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and intercellular adhesion molecule-1 (ICAM-1 after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.

  8. The neuroprotective effect of two statins: simvastatin and pravastatin on a streptozotocin-induced model of Alzheimer's disease in rats.

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    Tramontina, Ana Carolina; Wartchow, Krista Minéia; Rodrigues, Letícia; Biasibetti, Regina; Quincozes-Santos, André; Bobermin, Larissa; Tramontina, Francine; Gonçalves, Carlos-Alberto

    2011-11-01

    Astrocytes play a fundamental role in glutamate metabolism by regulating the extracellular levels of glutamate and intracellular levels of glutamine. They also participate in antioxidant defenses, due to the synthesis of glutathione, coupled to glutamate metabolism. Although the cause of Alzheimer's disease (AD) remains elusive, some changes in neurochemical parameters, such as glutamate uptake, glutamine synthetase activity and glutathione have been investigated in this disease. A possible neuroprotective effect of two statins, simvastatin and pravastatin (administered p.o.), was evaluated using a model of dementia, based on the intracerebroventricular (ICV) administration of streptozotocin (STZ), and astrocyte parameters were determined. We confirmed a cognitive deficit in rats submitted to ICV-STZ, and a prevention of this deficit by statin administration. Moreover, both statins were able to prevent the decrease in glutathione content and glutamine synthetase activity in this model of AD. Interestingly, simvastatin increased per se glutamate uptake activity, while both statins increased glutamine synthetase activity per se. These results support the idea that these drugs could be effective for the prevention of alterations observed in the STZ dementia model and may contribute to reduce the cognitive impairment and brain damage observed in AD patients.

  9. Linalool as a neuroprotective agent against acrylamide-induced neurotoxicity in Wistar rats.

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    Mehri, Soghra; Meshki, Mohammad Ali; Hosseinzadeh, Hossein

    2015-04-01

    Acrylamide (ACR) is a water-soluble monomer which has broad application in different industries and also can form in food during heating process. This monomer is a potent neurotoxic and damages the central and the peripheral nervous system in human and animals. Oxidative stress has been mentioned as an important pathway in ACR neurotoxicity, therefore the purpose of the current study was evaluation of possible effects of linalool which is a naturally enantiomer monoterpene compound. Linalool has shown antioxidant properties in several studies. Male Wistar rats were treated with ACR (50 mg/kg ip) alone or with linalool (12.5, 25, 50 and 100 mg/kg ip) for 11 days. In another 2 groups rats were treated with linalool (12.5 mg/kg ip) 3 days after and before ACR administration. Then behavior index (gait score) was examined for rats. After that, rats were sacrified and molondialdehyde (MDA) as a marker of lipid peroxidation and glutathione (GSH) content were determined in brain tissue. Exposure to ACR led to severe gait abnormalities and treatment with linalool significantly reduced abnormalities. ACR reduced GSH content and increased level of MDA in cerebral cortex. Linalool increased GSH content while decreased ACR-induced lipid peroxidation in rat brain tissue and the best protocols were initiation of supplementation before or simultaneous with ACR administration.

  10. Neuroprotective efficacy of pharmacological pretreatment and antidotal treatment in tabun-poisoned rats.

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    Krejcová, G; Kassa, J

    2003-03-14

    To study the influence of pharmacological pretreatment (PANPAL) and antidotal treatment (obidoxime plus atropine) on tabun-induced neurotoxicity, male albino rats were poisoned with a lethal dose of tabun (280 microg/kg i.m.; 100% of LD(50) value) and observed at 24 h and 7 days following tabun challenge. The neurotoxicity of tabun was evaluated using a functional observational battery (FOB) and an automatic measurement of motor activity. Pharmacological pretreatment as well as antidotal treatment were able to eliminate most of tabun-induced neurotoxic effects observed at 24 h following tabun poisoning. However, there was not significant difference between the efficacy of PANPAL and antidotal treatment to eliminate tabun-induced neurotoxicity in rats. The combination of PANPAL pretreatment and antidotal treatment seems to be slightly more effective in the elimination of tabun-induced neurotoxicity in rats at 24 h following tabun challenge in comparison with the administration of PANPAL pretreatment or antidotal treatment alone. At 7 days following tabun poisoning, very few neurotoxic signs in tabun-poisoned rats were observed regardless of administration of pharmacological pretreatment or antidotal treatment. Thus, our findings confirm that the combination of pharmacological pretreatment and antidotal treatment is not only able to protect the experimental animals from the lethal effects of tabun but also to eliminate most of tabun-induced signs of neurotoxicity in tabun-poisoned rats.

  11. Neuroprotective role of hydroalcoholic extract of Vitis vinifera against aluminium-induced oxidative stress in rat brain.

    Science.gov (United States)

    Lakshmi, B V S; Sudhakar, M; Anisha, M

    2014-03-01

    The present study was designed to examine the protective potential of hydroalcoholic extract of Vitis vinifera in ameliorating the alterations induced by aluminium (Al) on behavioural and neurochemical indices. Al was given orally (100mg/kg b.wt./day) whereas V. vinifera extract was administered through diet (400mg/kg, p.o.) to rats for a total duration of 45 days. Passive avoidance and open field tests revealed significant alterations in the short-term memory and cognitive behaviour in rats treated with Al. Further, locomotor as well as muscular activities were also found to be significantly affected. Co-administration of V. vinifera extract with Al caused significant improvement in the short-term memory, cognition, anxiety, locomotion and muscular activity. Al exposure led to a significant decrease in the acetylcholinesterase activity in the brain, increase in serum glucose, TG, TC, ALP and ALT. Anti-oxidant parameters-reduced glutathione, catalase and glutathione reductase levels were also found to be significantly decreased but the levels of lipid peroxidation was significantly increased in brain following Al treatment. V. vinifera extract supplementation to Al treated animals caused a significant improvement in the activity of enzyme acetylcholinesterase which was altered by Al. Serum glucose, TG, TC, ALP and ALT were brought back to normal levels. Further, V. vinifera extract when given along with Al was also able to regulate the levels of Anti-oxidant parameters in brain and the values were found close to the normal controls. Histopathological studies revealed neurodegeneration and vacuolated cytoplasm after Al treatment. Therefore, the study strengthens the hypothesis that V. vinifera extract can be used as a neuroprotectant during Al induced neurotoxicity.

  12. Neuroprotective effects of lycopene in spinal cord injury in rats via antioxidative and anti-apoptotic pathway.

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    Hu, Wei; Wang, Hongbo; Liu, Zhenfeng; Liu, Yanlu; Wang, Rong; Luo, Xiao; Huang, Yifei

    2017-03-06

    Oxidative damage induced-mitochondrial dysfunction and apoptosis has been widely studied in spinal cord injury (SCI). Lycopene, a polyunsaturated hydrocarbon, has the highest antioxidant capacity compared to the other carotenoids. However, the role of lycopene in SCI is unknown. In the present study, we evaluated the antioxidant effects of lycopene on mitochondrial dysfunction and apoptosis following T10 contusion SCI in rats. The rats were randomized into 5 groups: the sham group, the SCI group and the SCI pre-treated with lycopene (5, 10, or 20mg/kg) group. The SCI group showed increased malondialdehyde (MDA) content, decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) ability, which indicated that SCI could induce oxidative damage. What's more, the SCI group showed decreased mRNA expression of cytochrome b and mitochondrial transcription factor A (Tfam), and decreased mitochondrial membrane potential (ΔYm), which indicated that SCI could induce mitochondrial dysfunction. Besides, the SCI group showed decreased protein expression of bcl-2 and mitochondrial cytochrome C, increased protein expression of cytosolic cytochrome C, cleaved caspase-9, cleaved caspase-3 and bax, and increased TUNEL-positive cell numbers, which indicated that SCI could induce cell apoptosis. Fortunately, the lycopene treatment significantly ameliorated oxidative damage, mitochondrial dysfunction and cell apoptosis via the reversion of those parameters described above in the dose of lycopene of 10 and 20mg/kg. In addition, lycopene significantly ameliorated the hind limb motor disturbances in the SCI+lyco10 group and the SCI+lyco20 group compared with the SCI group. These results suggested that lycopene administration could improve total antioxidant status and might have neuroprotective effects on SCI.

  13. Neuroprotective Mechanisms Activated in Non-seizing Rats Exposed to Sarin

    Science.gov (United States)

    2015-06-04

    Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States a r t i c l e i n f o Article history : Accepted...Paniagua, C., Vacas, E., Fernández, B., 2007. Effect of ammonia , glutamine, and serum on calcineurin, p38MAPK-diP, GADD153/CHOP10, and CNTF in primary rat...T., Ishikura, T., Fujihara, H., Nomura, M., Hachisuka, K., Ueta, Y., 2011. Upregulation of arginine vasopressin synthesis in the rat hypothalamus

  14. Early applied electric field stimulation attenuates secondary apoptotic responses and exerts neuroprotective effects in acute spinal cord injury of rats.

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    Zhang, C; Zhang, G; Rong, W; Wang, A; Wu, C; Huo, X

    2015-04-16

    Injury potential, which refers to a direct current voltage between intact and injured nerve ends, is mainly caused by injury-induced Ca2+ influx. Our previous studies revealed that injury potential increased with the onset and severity of spinal cord injury (SCI), and an application of applied electric field stimulation (EFS) with the cathode distal to the lesion could delay and attenuate injury potential formation. As Ca2+ influx is also considered as a major trigger for secondary injury after SCI, we hypothesize that EFS would protect an injured spinal cord from secondary injury and consequently improve functional and pathological outcomes. In this study, rats were divided into three groups: (1) sham group, laminectomy only; (2) control group, subjected to SCI only; and (3) EFS group, received EFS immediately post-injury with the injury potential modulated to 0±0.5 mV by EFS. Functional recovery of the hind limbs was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results revealed that EFS-treated rats exhibited significantly better locomotor function recovery. Luxol fast blue staining was performed to assess the spared myelin area. Immunofluorescence was used to observe the number of myelinated nerve fibers. Ultrastructural analysis was performed to evaluate the size of myelinated nerve fibers. Findings showed that the EFS group rats exhibited significantly less myelin loss and had larger and more myelinated nerve fibers than the control group rats in dorsal corticospinal tract (dCST) 8 weeks after SCI. Furthermore, we found that EFS inhibited the activation of calpain and caspase-3, as well as the expression of Bax, as detected by Western blot analysis. Moreover, EFS decreased cellular apoptosis, as measured by TUNEL, within 4 weeks post-injury. Results suggest that early EFS could significantly reduce spinal cord degeneration and improve functional and historical recovery. Furthermore, these neuroprotective effects may be related to

  15. The role of peroxisome proliferator-activated receptor and effects of its agonist, pioglitazone, on a rat model of optic nerve crush: PPARγ in retinal neuroprotection.

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    Juming Zhu

    Full Text Available It has been shown that peroxisome proliferators-activated receptor gamma (PPARγ is beneficial for central nervous system injury. However its role on optic nerve injury remains unknown. In the present study, we examined the change of PPARγ expression in rat retina following optic nerve injury and investigated the effect of pioglitazone (Pio, a PPARγ agonist, on retinal ganglion cells (RGCs neuroprotection using a rat optic nerve crush (ONC model. Our results showed that PPARγ mRNA and protein levels were increased after ONC, and most of PPARγ-immunoreactive cells colocalized with Müller cells. Pio treatment significantly enhanced the number of surviving RGCs and inhibited RGCs apoptosis induced by ONC. However, when PPARγ antagonist GW9662 was used, these neuroprotective effects were abolished. In addition, pio attenuated Müller cell activation after ONC. These results indicate that PPARγ appears to protect RGCs from ONC possibly via the reduction of Müller glial activation. It provides evidence that activation of PPARγ may be a potential alternative treatment for RGCs neuroprotection.

  16. Anxiolytic and neuroprotective effects of the Traditional Chinese Medicinal formulation Dan-zhi-xiao-yao-san in a rat model of chronic stress.

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    Cao, Guo-Ping; Gui, Dan; Fu, Lu-Di; Guo, Zhou-Ke; Fu, Wen-Jun

    2016-08-01

    Dan-zhi-xiao-yao-san is a Traditional Chinese Medicinal formulation widely used for the treatment of neuropsychological disorders. The present study examined the anxiolytic and neuroprotective effects of Dan-zhi-xiao-yao-san in a rat model of chronic stress. The results of an elevated plus maze test showed that Dan‑zhi‑xiao‑yao‑san significantly attenuated the levels of anxiety-induced stress as evidenced by increases in the time spent in the open arm region, as well as the percentage of entries into this area. In addition, Dan-zhi-xiao-yao-san alleviated stress‑induced neuronal death, as indicated by histological examination. Furthermore, mechanistic studies suggested that the anxiolytic and neuroprotective effects of Dan-zhi-xiao-yao-san may be mediated via attenuation of chronic stress‑induced upregulation of α‑synuclein and corticosterone, and downregulation of protein phosphatase 2A (PP2A) in the hippocampal region of the brain at the mRNA and protein level. In addition, Dan‑zhi‑xiao‑yao‑san decreased the serum levels of stress‑induced corticosterone in the model animals. In conclusion, the present study demonstrated that Dan‑zhi‑xiao‑yao‑san exerted anxiolytic and neuroprotective effects in a rat model of chronic stress via attenuation of stress‑induced upregulation of α‑synuclein and corticosterone, and downregulation of PP2A in the hippocampus.

  17. Therapeutic window of opportunity for the neuroprotective effect of valproate versus the competitive AMPA receptor antagonist NS1209 following status epilepticus in rats.

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    Langer, Melanie; Brandt, Claudia; Zellinger, Christina; Löscher, Wolfgang

    2011-01-01

    Epileptogenesis, i.e., the process leading to epilepsy, is a presumed consequence of brain insults including head trauma, stroke, infections, tumors, status epilepticus (SE), and complex febrile seizures. Typically, brain insults produce morphological and functional alterations in the hippocampal formation, including neurodegeneration in CA1, CA3, and, most consistently, the dentate hilus. Most of these alterations develop gradually, over several days, after the insult, providing a therapeutic window of opportunity for neuroprotective agents in the immediate post-injury period. We have previously reported that prolonged (four weeks) treatment with the antiepileptic drug valproate (VPA) after SE prevents hippocampal damage and most of the behavioral alterations that occur after brain insult, but not the development of spontaneously occurring seizures. These data indicated that VPA, although not preventing epilepsy, might be an effective disease-modifying treatment following brain insult. The present study was designed to (1) determine the therapeutic window for the neuroprotective effect of VPA after SE; (2) compare the efficacy of different intermittent i.p. versus continuous i.v. VPA treatment protocols; and (3) compare VPA with the glutamate (AMPA) receptor antagonist NS1209. As in our previous study with VPA, SE was induced by sustained electrical stimulation of the basolateral amygdala in rats and terminated after 4 h by diazepam. In vehicle controls, >90% of the animals developed significant neurodegeneration in the dentate hilus, whereas damage in CA1 and CA3 was more variable. Hilar parvalbumin-expressing interneurons were more sensitive to the effects of seizures than somatostatin-stained hilar interneurons or hilar mossy cells. Among the various VPA treatment protocols, continuous infusion of VPA for 24 immediately following the SE was the most effective neuroprotective treatment, preventing most of the neuronal damage. Infusion with NS1209 for 24 h

  18. Functional identification of neuroprotective molecules.

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    Cheng Dai

    Full Text Available The central nervous system has the capacity to activate profound neuroprotection following sub-lethal stress in a process termed preconditioning. To gain insight into this potent survival response we developed a functional cloning strategy that identified 31 putative neuroprotective genes of which 28 were confirmed to provide protection against oxygen-glucose deprivation (OGD or excitotoxic exposure to N-methyl-D-aspartate (NMDA in primary rat cortical neurons. These results reveal that the brain possesses a wide and diverse repertoire of neuroprotective genes. Further characterization of these and other protective signals could provide new treatment opportunities for neurological injury from ischemia or neurodegenerative disease.

  19. The Protective Role of Mecobalamin Following Optic Nerve Crush in Adult Rats

    Institute of Scientific and Technical Information of China (English)

    Xiangmei Kong; Xinghuai Sun; Jinjun Zhang

    2004-01-01

    Purpose: To evaluate the potential for Mecobalamin as a neuroprotective agent in optic nerve crush injury.Methods: Twenty-four adult Sprague-Dawley rats were randomly divided into four groups.One group acted as normal controls, while in the other three groups the right eye was subjected to optic nerve crush injury. Of the three crush injury groups one group received no treatment, while the other two groups received intramuscular injections of VitaminB12 or Mecobalamin (10μg) immediately after crush injury and then every two days. All the rats were sacrificed one month post-treatment, and the eyes attached with optic nerves were removed for histology. The morphological changes of optic nerve axons and retinal ganglion cells (RGCs) were assessed under light microscope (LM) and transmission electromicroscope (TEM). The numbers of axons and RGCs were counted.Results: In this study we demonstrate the potential for Mecobalamin as a neuroprotective agent following optic nerve crush injury. We show here that the axons of optic nerves were loose in structure or destroyed. The mitochondria of the RGCs was swollen, and the Nissel body was less evident after the crush injury. Moreover, the number of axons and RGCs was significantly reduced (P < 0.001). However, these changes were less dramatic after the Mecobalamin-treatment. More axons and RGCs were remained in the group than those in the untreated injury group (P = 0.010 and 0.003 respectively), and those in the VitaminB12-treated group (P=0.037 and 0.035 respectively). More significantly, there were newly formed axons found in the Mecobalamin-treated group.Conclusions: Optic nerve crush injury in rats causes the loss of the axons and RGCs but this may be ameliorated by treatment with Mecobalamin.

  20. A comparison of the neuroprotective efficacy of newly developed oximes (K117, K127) and currently available oxime (obidoxime) in tabun-poisoned rats.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Musilek, Kamil; Kuca, Kamil; Jung, And Young-Sik

    2009-03-01

    The potency of newly developed bispyridinium compounds (K117, K127) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with currently available oxime (obidoxime) using functional observational battery. The neuroprotective effects of atropine alone and atropine combined with one of three bispyridinium oximes (K117, K127, obidoxime) on rats poisoned with tabun at a sublethal dose (180 microg/kg i.m.; 80% of LD(50) value) were studied. Tabun-induced neurotoxicity was monitored using a functional observational battery and automatic measurement of motor activity at 24 h following tabun challenge. The results indicated that all tested oximes combined with atropine enabled tabun-poisoned rats to survive 24 h following tabun challenge while one tabun-poisoned rats died within 24 h after tabun poisoning when the rats were treated with atropine alone. Newly developed oxime K127 combined with atropine was the most effective in decreasing tabun-induced neurotoxicity in the case of sublethal poisonings among all oximes tested. Nevertheless, the differences of neuroprotective efficacy between K127 and obidoxime are not sufficient to replace obidoxime by K127 for the treatment of acute tabun poisonings.

  1. Neuroprotective Potential of Superparamagnetic Iron Oxide Nanoparticles Along with Exposure to Electromagnetic Field in 6-OHDA Rat Model of Parkinson's Disease.

    Science.gov (United States)

    Umarao, Preeti; Bose, Samrat; Bhattacharyya, Supti; Kumar, Anil; Jain, Suman

    2016-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting mainly the dopaminergic neurons of the substantia nigra leading to various motor and non-motor deficits. We explored the neuroprotective potential of superparamagnetic iron oxide nanoparticles (IONPs) along with exposure to EMF in 6-OHDA rat model of PD. IONPs were implanted at the site of lesion and 24 h thereafter the rats were exposed to magnetic fields 2 h/day for one week. Bilateral lesions of the striatum were made with 6-OHDA. The rats in all the intervention groups improved progressively over the days and by post-surgery day 4 they were active and bright. We observed a significant beneficial effect of the IONPs implantation and MF exposure on feeding behavior, gait and postural stability. There was a significant enhancement of mitochondrial function and attenuation of lesion volume in all the intervention groups as compared to PD. The results demonstrate neuroprotective effect of iron oxide nanoparticle implantation and magnetic field exposure in an in vivo 6-OHDA rat model of PD.

  2. Neuroprotection of the leaf and stem of Vitis amurensis and their active compounds against ischemic brain damage in rats and excitotoxicity in cultured neurons.

    Science.gov (United States)

    Kim, Joo Youn; Jeong, Ha Yeon; Lee, Hong Kyu; Kim, SeungHwan; Hwang, Bang Yeon; Bae, KiHwan; Seong, Yeon Hee

    2012-01-15

    Vitis amurensis (Vitaceae) has been reported to have anti-oxidant and anti-inflammatory activities. The present study investigated a methanol extract from the leaf and stem of V. amurensis for neuroprotective effects on cerebral ischemic damage in rats and on excitotoxicity induced by glutamate in cultured rat cortical neurons. Transient focal cerebral ischemia was induced by 2h middle cerebral artery occlusion followed by 24h reperfusion (MCAO/reperfusion) in rats. Orally administered V. amurensis (25-100 mg/kg) reduced MCAO/reperfusion-induced infarct and edema formation, neurological deficits, and neuronal death. Depletion of glutathione (GSH) level and lipid peroxidation induced by MCAO/reperfusion was inhibited by administration of V. amurensis. The increase of phosphorylated mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2), and pro-apoptotic proteins and the decrease of anti-apoptotic protein in MCAO/reperfusion rats were significantly inhibited by treatment with V. amurensis. Exposure of cultured cortical neurons to 500 μM glutamate for 12h induced neuronal cell death. V. amurensis (1-50 μg/ml) and (+)-ampelopsin A, γ-2-viniferin, and trans-ε-viniferin isolated from the leaf and stem of V. amurensis inhibited glutamate-induced neuronal death, the elevation of intracellular calcium ([Ca(2+)](i)), the generation of reactive oxygen species (ROS), and changes of apoptosis-related proteins in cultured cortical neurons, suggesting that the neuroprotective effect of V. amurensis may be partially attributed to these compounds. These results suggest that the neuroprotective effect of V. amurensis against focal cerebral ischemic injury might be due to its anti-apoptotic effect, resulting from anti-excitotoxic, anti-oxidative, and anti-inflammatory effects and that the leaf and stem of V. amurensis have possible therapeutic roles for preventing neurodegeneration in stroke.

  3. Pituitary adenylate cyclase-activating polypeptide (PACAP) has a neuroprotective function in dopamine-based neurodegeneration in rat and snail parkinsonian models

    Science.gov (United States)

    Kiss, Tibor; Jungling, Adel

    2017-01-01

    ABSTRACT Pituitary adenylate cyclase-activating polypeptide (PACAP) rescues dopaminergic neurons from neurodegeneration and improves motor changes induced by 6-hydroxy-dopamine (6-OHDA) in rat parkinsonian models. Recently, we investigated the molecular background of the neuroprotective effect of PACAP in dopamine (DA)-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. Behavioural activity, monoamine (DA and serotonin), metabolic enzyme (S-COMT, MB-COMT and MAO-B) and PARK7 protein concentrations were measured before and after PACAP treatment in both models. Locomotion and feeding activity were decreased in rotenone-treated snails, which corresponded well to findings obtained in 6-OHDA-induced rat experiments. PACAP was able to prevent the behavioural malfunctions caused by the toxins. Monoamine levels decreased in both models and the decreased DA level induced by toxins was attenuated by ∼50% in the PACAP-treated animals. In contrast, PACAP had no effect on the decreased serotonin (5HT) levels. S-COMT metabolic enzyme was also reduced but a protective effect of PACAP was not observed in either of the models. Following toxin treatment, a significant increase in MB-COMT was observed in both models and was restored to normal levels by PACAP. A decrease in PARK7 was also observed in both toxin-induced models; however, PACAP had a beneficial effect only on 6-OHDA-treated animals. The neuroprotective effect of PACAP in different animal models of Parkinson's disease is thus well correlated with neurotransmitter, enzyme and protein levels. The models successfully mimic several, but not all etiological properties of the disease, allowing us to study the mechanisms of neurodegeneration as well as testing new drugs. The rotenone and 6-OHDA rat and snail in vivo parkinsonian models offer an alternative method for investigation of the molecular mechanisms of neuroprotective agents, including PACAP. PMID:28067625

  4. Pituitary adenylate cyclase-activating polypeptide (PACAP) has a neuroprotective function in dopamine-based neurodegeneration in rat and snail parkinsonian models.

    Science.gov (United States)

    Maasz, Gabor; Zrinyi, Zita; Reglodi, Dora; Petrovics, Dora; Rivnyak, Adam; Kiss, Tibor; Jungling, Adel; Tamas, Andrea; Pirger, Zsolt

    2017-02-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) rescues dopaminergic neurons from neurodegeneration and improves motor changes induced by 6-hydroxy-dopamine (6-OHDA) in rat parkinsonian models. Recently, we investigated the molecular background of the neuroprotective effect of PACAP in dopamine (DA)-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. Behavioural activity, monoamine (DA and serotonin), metabolic enzyme (S-COMT, MB-COMT and MAO-B) and PARK7 protein concentrations were measured before and after PACAP treatment in both models. Locomotion and feeding activity were decreased in rotenone-treated snails, which corresponded well to findings obtained in 6-OHDA-induced rat experiments. PACAP was able to prevent the behavioural malfunctions caused by the toxins. Monoamine levels decreased in both models and the decreased DA level induced by toxins was attenuated by ∼50% in the PACAP-treated animals. In contrast, PACAP had no effect on the decreased serotonin (5HT) levels. S-COMT metabolic enzyme was also reduced but a protective effect of PACAP was not observed in either of the models. Following toxin treatment, a significant increase in MB-COMT was observed in both models and was restored to normal levels by PACAP. A decrease in PARK7 was also observed in both toxin-induced models; however, PACAP had a beneficial effect only on 6-OHDA-treated animals. The neuroprotective effect of PACAP in different animal models of Parkinson's disease is thus well correlated with neurotransmitter, enzyme and protein levels. The models successfully mimic several, but not all etiological properties of the disease, allowing us to study the mechanisms of neurodegeneration as well as testing new drugs. The rotenone and 6-OHDA rat and snail in vivo parkinsonian models offer an alternative method for investigation of the molecular mechanisms of neuroprotective agents, including PACAP.

  5. Computational Insights into The Neuroprotective Action of Riluzole on 3-Acetylpyridine-Induced Ataxia in Rats

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    Mahyar Janahmadi

    2013-01-01

    Full Text Available Objective: Intra-peritoneal administration of riluzole has been shown to preserve the membrane properties and firing characteristics of Purkinje neurons in a rat model of cerebellar ataxia induced by 3-acetylpyridine (3-AP. However, the exact mechanism(s by which riluzole restores the normal electrophysiological properties of Purkinje neurons is not completely understood. Changes in the conductance of several ion channels, including the BK channels, have been proposed as a neuro protective target of riluzole. In this study, the possible cellular effects of riluzole on Purkinje cells from 3-AP-induced ataxic rats that could be responsible for its neuro protective action have been investigated by computer simulations.Materials and Methods: This is a computational stimulation study. The simulation environment enabled a change in the properties of the specific ion channels as the possible mechanism of action of riluzole. This allowed us to study the resulted changes in the firing activity of Purkinje cells without concerns about its other effects and interfering parameters in the experiments. Simulations were performed in the NEURON environment (Version 7.1 in a time step of 25 μs; analyses were conducted using MATLAB r2010a (The Mathworks. Data were given as mean ± SEM. Statistical analyses were performed by the student’s t test, and differences were considered significant if p<0.05.Results: The computational findings demonstrated that modulation of an individual ion channel current, as suggested by previous experimental studies, should not be considered as the only possible target for the neuro protective effects of riluzole to restore the normal firing activity of Purkinje cells from ataxic rats.Conclusion: Changes in the conductance of several potassium channels, including voltage-gated potassium (Kv1, Kv4 and big Ca2+-activated K+ (BK channels may be responsible for the neuro protective effect of riluzole against 3-AP induced alterations in

  6. The Neuroprotective Benefits of Central Adenosine Receptor Stimulation in a Soman Nerve Agent Rat Model

    Science.gov (United States)

    2014-04-01

    transponder between the shoulder blades subcutaneously (Bio Medic Data Systems Inc., Seaford, DE) and then had wire-electrodes implanted into the...recorded from EEG and used to detect seizure onset. The electrodes implanted into the rat’s skull were connected to recording leads via a connecting plug...that attached to the rat’s head with dental cement. At the time of experiment, the rats were placed in individual recording chambers (43 x 30 x 25 cm

  7. Neuroprotective effect of hesperidin on aluminium chloride induced Alzheimer's disease in Wistar rats.

    Science.gov (United States)

    Justin Thenmozhi, Arokiasamy; Raja, Tharsius Raja William; Janakiraman, Udaiyappan; Manivasagam, Thamilarasan

    2015-04-01

    The present study was aimed to evaluate the protective effect of hesperidin (Hes) on aluminium chloride (AlCl3) induced neurobehavioral and pathological changes in Alzheimeric rats. Intraperitonial injection of AlCl3 (100 mg/kg body weight) for 60 days significantly elevated the levels of aluminium (Al), activity of acetylcholinesterase (AChE) and protein expressions of amyloid precursor protein (APP), β amyloid (Aβ 1-42), β and γ secretases as compared to control group in hippocampus and cortex of rat brain. Hes administration orally along with AlCl3 injection for 60 days, significantly revert the Al concentration, AChE activity and Aβ synthesis-related molecules in the studied brain regions. Our results showed that aluminum exposure was significantly reduced the spontaneous locomotor and exploratory activities in open field test and enhanced the learning and memory impairments in morris water maze test. The behavioral impairments caused by aluminum were significantly attenuated by Hes. The histopathological studies in the hippocampus and cortex of rat brain also supported that Hes (100 mg/kg) markedly reduced the toxicity of AlCl3 and preserved the normal histoarchitecture pattern of the hippocampus and cortex. From these results, it is concluded that hesperidin can reverse memory loss caused by aluminum intoxication through attenuating AChE activity and amyloidogenic pathway.

  8. Neuroprotective Effect of Xueshuantong for Injection (Lyophilized in Transient and Permanent Rat Cerebral Ischemia Model

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    Xumei Wang

    2015-01-01

    Full Text Available Xueshuantong for Injection (Lyophilized (XST, a Chinese Materia Medica standardized product extracted from Panax notoginseng (Burk., is used extensively for the treatment of cerebrovascular diseases such as acutely cerebral infarction clinically in China. In the present study, we evaluated the acute and extended protective effects of XST in different rat cerebral ischemic model and explored its effect on peroxiredoxin (Prx 6-toll-like receptor (TLR 4 signaling pathway. We found that XST treatment for 3 days could significantly inhibit transient middle cerebral artery occlusion (MCAO induced infarct volume and swelling percent and regulate the mRNA expression of interleukin-1β (IL-1β, IL-17, IL-23p19, tumor necrosis factor-α (TNFα, and inducible nitric oxide synthase (iNOS in brain. Further study demonstrated that treatment with XST suppressed the protein expression of peroxiredoxin (Prx 6-toll-like receptor (TLR 4 and phosphorylation level of p38 and upregulated the phosphorylation level of STAT3. In permanent MCAO rats, XST could reduce the infarct volume and swelling percent. Moreover, our results revealed that XST treatment could increase the rats’ weight and improve a batch of functional outcomes. In conclusion, the present data suggested that XST could protect against ischemia injury in transient and permanent MCAO rats, which might be related to Prx6-TLR4 pathway.

  9. Red Lentil Extract: Neuroprotective Effects on Perphenazine Induced Catatonia in Rats

    Science.gov (United States)

    Tarahomi, Shahram; Arzi, Ardeshir; Goudarzi, Mehdi; Bahadoram, Mohammad; Rashidi-Nooshabadi, Mohammadreza

    2016-01-01

    Introduction Parkinsonism is a neurodegenerative disease that is defined by certain symptoms such as muscle rigidity, impaired movement, catatonia, tremor and disorientation of body. Aim The aim was to investigate the effect of red lentil extract on perphenazine-induced Catatonia in model of rat. Materials and Methods This experimental study was done on 48 male albino rats (weight 180–200g) of the Sprague-Dawley strain. Animals were randomly divided into six groups and were pre-treated with a single dose of red lentil extract (200, 400, 800 and 1000 mg/kg), most effective dose of bromocriptine (30mg/kg) and normal saline (5ml/kg) via intraperitoneal (IP) route. perphenazine (5 mg/kg) was after 30 minutes, administered (IP) to induce catatonia. The scoring method of Morpurgo was used to determine the muscular rigidity of animals. Results The results showed that the 200mg/kg red lentil extract treated group had no significant reduction in catatonic responses after perphenazine administration in comparison with control group while the groups that received 800 and 1000mg/kg of red lentil extract showed significant difference (pCatatonia induced by perphenazine in rats. So this extract may be probably beneficial for catatonia in Parkinsonism. PMID:27504309

  10. Antiapoptotic and neuroprotective role of Curcumin in Pentylenetetrazole (PTZ) induced kindling model in rat.

    Science.gov (United States)

    Saha, Lekha; Chakrabarti, Amitava; Kumari, Sweta; Bhatia, Alka; Banerjee, Dibyojyoti

    2016-02-01

    Kindling, a sub threshold chemical or electrical stimulation, increases seizure duration and enhances accompanied behavior until it reaches a sort of equilibrium state. The present study aimed to explore the effect of curcumin on the development of kindling in PTZ kindled rats and its role in apoptosis and neuronal damage. In a PTZ kindled Wistar rat model, different doses of curcumin (100, 200 and 300 mg/kg) were administrated orally one hour before the PTZ injections on alternate day during the whole kindling days. The following parameters were compared between control and experimental groups: the course of kindling, stages of seizures, Histopathological scoring of hippocampus, antioxidant parameters in the hippocampus, DNA fragmentation and caspase-3 expression in hippocampus, and neuron-specific enolase in the blood. One way ANOVA followed by Bonferroni post hoc analysis and Fischer's Exact test were used for statistical analyses. PTZ, 30 mg/kg, induced kindling in rats after 32.0 ± 1.4 days. Curcumin showed dose-dependent anti-seizure effect. Curcumin (300 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure score and decreased the number of myoclonic jerks. PTZ kindling induced a significant neuronal injury, oxidative stress and apoptosis which were reversed by pretreatment with curcumin in a dose-dependent manner. Our study suggests that curcumin has a potential antiepileptogenic effect on kindling-induced epileptogenesis.

  11. Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury.

    Science.gov (United States)

    Lu, Xi-Chun May; Shear, Deborah A; Deng-Bryant, Ying; Leung, Lai Yee; Wei, Guo; Chen, Zhiyong; Tortella, Frank C

    2016-03-01

    Brain hypothermia has been considered as a promising alternative to whole-body hypothermia in treating acute neurological disease, for example, traumatic brain injury. Previously, we demonstrated that 2-hours selective brain cooling (SBC) effectively mitigated acute (≤24 hours postinjury) neurophysiological dysfunction induced by a penetrating ballistic-like brain injury (PBBI) in rats. This study evaluated neuroprotective effects of extended SBC (4 or 8 hours in duration) on sub-acute secondary injuries between 3 and 21 days postinjury (DPI). SBC (34°C) was achieved via extraluminal cooling of rats' bilateral common carotid arteries (CCA). Depending on the experimental design, SBC was introduced either immediately or with a 2- or 4-hour delay after PBBI and maintained for 4 or 8 hours. Neuroprotective effects of SBC were evaluated by measuring brain lesion volume, axonal injury, neuroinflammation, motor and cognitive functions, and post-traumatic seizures. Compared to untreated PBBI animals, 4 or 8 hours SBC treatment initiated immediately following PBBI produced comparable neuroprotective benefits against PBBI-induced early histopathology at 3 DPI as evidenced by significant reductions in brain lesion volume, axonal pathology (beta-amyloid precursor protein staining), neuroinflammation (glial fibrillary acetic protein stained-activated astrocytes and rat major histocompatibility complex class I stained activated microglial cell), and post-traumatic nonconvulsive seizures. In the later phase of the injury (7-21 DPI), significant improvement on motor function (rotarod test) was observed under most SBC protocols, including the 2-hour delay in SBC initiation. However, SBC treatment failed to improve cognitive performance (Morris water maze test) measured 13-17 DPI. The protective effects of SBC on delayed axonal injury (silver staining) were evident out to 14 DPI. In conclusion, the CCA cooling method of SBC produced neuroprotection measured across multiple

  12. Neuroprotection in selective focal ischemia in rats by nitrates, an alternative redox manipulation on nitric oxide: experimental model.

    Science.gov (United States)

    Ramos-Zúñiga, R; Velázquez-Santana, H; Mercado-Pimentel, R; Cerda-Camacho, F

    1998-09-01

    The recent advances in the histopathology of ischemia have set forth new proposals, particularly in regard to excitotoxicity by the glutamate receptor, NMDA. The participation of the nitric oxide (NO) in normal and pathological conditions and its relationship with toxicity in ischemia, suggest new alternatives for the modulation of the NMDA receptor REDOX site through its pharmacologic manipulation. This event would potentially limit the consequences of the activation-calcium flow and the production of peroxoinitrite during the ischemic phenomenon. The present work delivers two proposals: 1) A modified technique to the ones that have been described, of endovascular, without craniectomy, for experimental cerebral ischemia in Wistar rats, and with particular harmful effect upon the hippocampus. 2) It promotes the use of nitrates as an additional alternative to other elements, in order to restrict excitotoxicity in the described experimental cerebral ischemia, and paying attention to CA1-CA2 of the hippocampus. This area, specially sensitive to hypoxia-ischemia, offers an excellent study option for focal, experimental, cerebral ischemia associated with toxicity mediated by excitatory amino acids, since it stores an important concentration of NMDA receptors (R1/R2 A) as well as endothelial nitric oxide synthase. Our parameters are supported by quantitative-qualitative cell analysis, and not by the extension of the stroke which offers a more objective perspective upon the assessment of the focal ischemic event. By means of this technique, these results confirm the extent of the ischemic injury to the cell at the level of the hippocampus compared to a control/basal group, P = 0.0006. Furthermore, it suggests a neuroprotective effect of isosorbide dinitrate since it preserves the viable cells, and limits the appearance of hypoxic-ischemic cells at the hippocampus when the middle cerebral artery (MCA) is occluded endovascularly, as compared to the animals with no treatment

  13. A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model.

    Science.gov (United States)

    Pinzon, Alberto; Marcillo, Alexander; Quintana, Ada; Stamler, Sarah; Bunge, Mary Bartlett; Bramlett, Helen M; Dietrich, W Dalton

    2008-12-03

    This study was initiated due to an NIH "Facilities of Research--Spinal Cord Injury" contract to support independent replication of published studies that could be considered for a clinical trial in time. Minocycline has been shown to have neuroprotective effects in models of central nervous system injury, including in a contusive spinal cord injury (SCI) model at the thoracic level. Beneficial effects of minocycline treatment included a significant improvement in locomotor behavior and reduced histopathological changes [Lee, S.M., Yune, T.Y., Kim, S.J., Park, D.O.W., Lee, Y.K., Kim, Y.C., Oh, Y.J., Markelonis, G.J., Oh, T.H., 2003. Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J Neurotrauma. 20, 1017-1027.] To verify these important observations, we repeated this study in our laboratory. The NYU (MASCIS) Impactor was used to produce a moderate cord lesion at the vertebral level T9-T10 (height 12.5 mm, weight 10 g), (n=45), followed by administration of minocycline, 90 mg/kg (group 1: minocycline IP, n=15; group 2: minocycline IV, n=15; group 3: vehicle IP, n=8; group 4: vehicle IV, n=7) immediately after surgery and followed by two more doses of 45 mg/kg/IP at 12 h and 24 h. Open field locomotion (BBB) and subscores were examined up to 6 weeks after SCI and cords were processed for quantitative histopathological analysis. Administration of minocycline after SCI did not lead to significant behavioral or histopathological improvement. Although positive effects with minocycline have been reported in several animal models of injury with different drug administration schemes, the use of minocycline following contusive SCI requires further investigation before clinical trials are implemented.

  14. Neuroprotective and antioxidant effects of curcumin in a ketamine-induced model of mania in rats.

    Science.gov (United States)

    Gazal, Marta; Valente, Matheus R; Acosta, Bruna A; Kaufmann, Fernanda N; Braganhol, Elizandra; Lencina, Claiton L; Stefanello, Francieli M; Ghisleni, Gabriele; Kaster, Manuella P

    2014-02-01

    Bipolar disorder (BD) is a chronic and debilitating illness characterized by recurrent manic and depressive episodes. Our research investigates the protective effects of curcumin, the main curcuminoid of the Indian spice turmeric, in a model of mania induced by ketamine administration in rats. Our results indicated that ketamine treatment (25 mg/kg, for 8 days) induced hyperlocomotion in the open-field test and oxidative damage in prefrontal cortex (PFC) and hippocampus (HP), evaluated by increased lipid peroxidation and decreased total thiol content. Moreover, ketamine treatment reduced the activity of the antioxidant enzymes superoxide dismutase and catalase in the HP. Pretreatment of rats with curcumin (20 and 50 mg/kg, for 14 days) or with lithium chloride (45 mg/kg, positive control) prevented behavioral and pro-oxidant effects induced by ketamine. These findings suggest that curcumin might be a good compound for preventive intervention in BD, reducing the episode relapse and the oxidative damage associated with the manic phase of this disorder.

  15. Resveratrol is neuroprotective and improves cognition in pentylenetetrazole-kindling model of epilepsy in rats

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    X J Meng

    2014-01-01

    Full Text Available S100B protein in serum and cerebral spinal fluid is increasingly used as a biochemical marker in early examinations after seizure to assess brain damage. Resveratrol, a nonflavonoid polyphenol, has been identified as a potent antiepileptic agent. However, a potential association between epilepsy with S100B protein in the cerebral spinal fluid and the sera of animal models lacks investigation. In this study, we evaluated the effects of resveratrol on behaviour and S100B protein levels in cerebral spinal fluid and serum in a rat model of chronic epilepsy induced via pentylenetetrazole kindling. By Morris water maze experiment analysis, we found that recovery of cognitive function in the resveratrol group (15 mg/kg/day, was significantly better than that of either the untreated or the vehicle groups. Further Nissl staining revealed that resveratrol significantly reduced pentylenetetrazole-induced death of neurons in the CA1 and CA3 regions of the hippocampus. Moreover, S100B protein levels in the cerebral spinal fluid and serum of rats treated with resveratrol were significantly reduced compared with the untreated and vehicle groups. These novel findings suggest an important mechanism of resveratrol and contribute to the treatment of epilepsy.

  16. PI3 kinase/Akt activation mediates estrogen and IGF-1 nigral DA neuronal neuroprotection against a unilateral rat model of Parkinson's disease.

    Science.gov (United States)

    Quesada, Arnulfo; Lee, Becky Y; Micevych, Paul E

    2008-04-01

    Recently, using the medial forebrain bundle (MFB) 6-hydroxydopmaine (6-OHDA) lesion rat model of Parkinson's disease (PD), we have demonstrated that blockade of central IGF-1 receptors (IGF-1R) attenuated estrogen neuroprotection of substantia nigra pars compacta (SNpc) DA neurons, but exacerbated 6-OHDA lesions in IGF-1 only treated rats (Quesada and Micevych [2004]: J Neurosci Res 75:107-116). This suggested that the IGF-1 system is a central mechanism through which estrogen acts to protect the nigrostriatal DA system. Moreover, these results also suggest that IGF-1R-induced intracellular signaling pathways are involved in the estrogen mechanism that promotes neuronal survival. In vitro, two convergent intracellular signaling pathways used by estrogen and IGF-1, the mitogen-activated protein kinase (MAPK/ERK), and phosphatidyl-inositol-3-kinase/Akt (PI3K/Akt), have been demonstrated to be neuroprotective. Continuous central infusions of MAPK/ERK and PI3K/Akt inhibitors were used to test the hypothesis that one or both of these signal transduction pathways mediates estrogen and/or IGF-1 neuroprotection of SNpc DA neurons after a unilateral administration of 6-OHDA into the MFB of rats. Motor behavior tests and tyrosine hydroxylase immunoreactivity revealed that the inhibitor of the PI3K/Akt pathway (LY294002) blocked the survival effects of both estrogen and IGF-1, while an inhibitor of the MAPK/ERK signaling (PD98059) was ineffective. Western blot analyses showed that estrogen and IGF-1 treatments increased PI3K/Akt activation in the SN; however, MAPK/ERK activation was decreased in the SN. Indeed, continuous infusions of inhibitors blocked phosphorylation of PI3K/Akt and MAPK/ERK. These findings indicate that estrogen and IGF-1-mediated SNpc DA neuronal protection is dependent on PI3K/Akt signaling, but not on the MAPK/ERK pathway.

  17. A diphenyl diselenide-supplemented diet and swimming exercise promote neuroprotection, reduced cell apoptosis and glial cell activation in the hypothalamus of old rats.

    Science.gov (United States)

    Leite, Marlon R; Cechella, José L; Pinton, Simone; Nogueira, Cristina W; Zeni, Gilson

    2016-09-01

    Aging is a process characterized by deterioration of the homeostasis of various physiological systems; although being a process under influence of multiple factors, the mechanisms involved in aging are not well understood. Here we investigated the effect of a (PhSe)2-supplemented diet (1ppm, 4weeks) and swimming exercise (1% of body weight, 20min per day, 4weeks) on proteins related to glial cells activation, apoptosis and neuroprotection in the hypothalamus of old male Wistar rats (27month-old). Old rats had activation of astrocytes and microglia which was demonstrated by the increase in the levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1) in hypothalamus. A decrease of B-cell lymphoma 2 (Bcl-2) and procaspase-3 levels as well as an increase of the cleaved PARP/full length PARP ratio (poly (ADP-ribose) polymerase, PARP) and the pJNK/JNK ratio (c-Jun N-terminal kinase, JNK) were observed. The levels of mature brain-derived neurotrophic factor (mBDNF), the pAkt/Akt ratio (also known as protein kinase B) and NeuN (neuronal nuclei), a neuron marker, were decreased in the hypothalamus of old rats. Old rats that received a (PhSe)2-supplemented diet and performed swimming exercise had the hypothalamic levels of Iba-1 and GFAP decreased. The combined treatment also increased the levels of Bcl-2 and procaspase-3 and decreased the ratios of cleaved PARP/full length PARP and pJNK/JNK in old rats. The levels of mBDNF and NeuN, but not the pAkt/Akt ratio, were increased by combined treatment. In conclusion, a (PhSe)2-supplemented diet and swimming exercise promoted neuroprotection in the hypothalamus of old rats, reducing apoptosis and glial cell activation.

  18. Neuroprotective effect of sodium ferulate and signal transduction mechanisms in the aged rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Ying JIN; En-zhi YAN; Xiao-ming LI; Ying FAN; Yan-jie ZHAO; Zhuo LIU; Wan-zhu LIU

    2008-01-01

    Aim: To investigate whether the age-related increase in interleukin-1β (IL-1β) and c-Jun N-terminal kinases (JNK) pathway was coupled with a decrease in cell survival signaling pathways and whether sodium ferulate (SF) treatment was ef-fective in preventing these age-associated changes. Methods: Groups of young and aged rats were fed for 4 weeks on a diet enriched in SF (100 mg/kg and 200 mg/kg per day). At the end of the period of dietary manipulation, Western blot-ting analysis was used to determine the expressions of IL-1β, phosphorylated mitogen-activated protein kinase kinase (MKK)4, phospho-JNK, phospho-c-Jun, phosphorylated extracellular signal-regulated kinase (ERK 1/2), phospho-MEK, phospho-Akt, phosphorylated ribosomal protein S6 protein kinase (p70S6K), and activated caspase-3 and caspase-7. Nissl staining was used to observe the morphological change in hippocampal CAI regions. Immunohistochemical techniques for glial fibrillary acidic protein (GFAP) and integrin αM (OX-42) were used to determine the astrocyte and microglia activation. Results: IL-1β protein levels, and phospho-MKK4, phospho-JNK1/2, and phospho-c-Jun were significantly enhanced in hippocampus prepared from age-matched control rats. Increased IL-1β production and JNKI/2 activation was accompanied by down-regulation of MEK/ERK1/2 pathway and Akt/p7OS6K pathway, leading to cell apoptosis assessed by activation of caspase-3. Significantly, treatment of aged rats with SF (100 mg/kg and 200 mg/kg per day) for 4 weeks prevented the age-related increase in IL-1β and IL-1β-induced JNK signaling pathway and also the age-related changes in ERK and Akt kinase. Conclusion: SF plays neuroprotec-tire roles through suppression of IL-1β and IL-1β-induced JNK signaling and upregulation of MEK/ERK1/2 and Akt/p70S6K survival pathways.

  19. Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

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    Castellano Bernardo

    2006-04-01

    Full Text Available Abstract Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn SOD or the control GFP transgenes 2 hours after intracortical N-methyl-D-aspartate (NMDA administration, and daily functional evaluation was performed. Moreover, 3 days after, lesion volume, neuronal degeneration and nitrotyrosine immunoreactivity were evaluated. Results Overexpression of Cu/Zn SOD transgene after NMDA administration showed improved functional outcome and a reduced lesion volume at 3 days post lesion. In secondary degenerative areas, increased neuronal survival as well as decreased numbers of degenerating neurons and nitrotyrosine immunoreactivity was seen. Interestingly, injection of the NLSCt vector carrying the control GFP transgene also displayed a significant neuroprotective effect but less pronounced. Conclusion When the appropriate levels of Cu/Zn SOD are expressed transiently after injury using the non-viral modular protein vector NLSCt a neuroprotective effect is seen. Thus recombinant modular protein vectors may be suitable for in vivo gene therapy, and Cu/Zn SOD should be considered as an interesting therapeutic transgene.

  20. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus.

    Science.gov (United States)

    Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

    2014-08-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions.

  1. Neuroprotective effect of a new DJ-1-binding compound against neurodegeneration in Parkinson's disease and stroke model rats

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    Yasui Hiroyuki

    2011-07-01

    Full Text Available Abstract Background Parkinson's disease (PD and cerebral ischemia are chronic and acute neurodegenerative diseases, respectively, and onsets of these diseases are thought to be induced at least by oxidative stress. PD is caused by decreased dopamine levels in the substantia nigra and striatum, and cerebral ischemia occurs as a result of local reduction or arrest of blood supply. Although a precursor of dopamine and inhibitors of dopamine degradation have been used for PD therapy and an anti-oxidant have been used for cerebral ischemia therapy, cell death progresses during treatment. Reagents that prevent oxidative stress-induced cell death are therefore necessary for fundamental therapies for PD and cerebral ischemia. DJ-1, a causative gene product of a familial form of PD, PARK7, plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in the onset of PD. Superfluous oxidation of cysteine at amino acid 106 (C106 of DJ-1 renders DJ-1 inactive, and such oxidized DJ-1 has been observed in patients with the sporadic form of PD. Results In this study, a compound, comp-23, that binds to DJ-1 was isolated by virtual screening. Comp-23 prevented oxidative stress-induced death of SH-SY5Y cells and primary neuronal cells of the ventral mesencephalon but not that of DJ-1-knockdown SH-SY5Y cells, indicating that the effect of the compound is specific to DJ-1. Comp-23 inhibited the production of reactive oxygen species (ROS induced by oxidative stress and prevented excess oxidation of DJ-1. Furthermore, comp-23 prevented dopaminergic cell death in the substantia nigra and restored movement abnormality in 6-hydroxyldopamine-injected and rotenone-treated PD model rats and mice. Comp-23 also reduced infarct size of cerebral ischemia in rats that had been induced by middle cerebral artery occlusion. Protective activity of comp-23 seemed to be stronger than that of previously identified compound B

  2. Neuroprotective Effects of Aged Garlic Extract on Cognitive Dysfunction and Neuroinflammation Induced by β-Amyloid in Rats

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    Nutchareeporn Nillert

    2017-01-01

    Full Text Available Neuroinflammation is pathological evidence of Alzheimer’s disease (AD that likely starts as a host defense response to the damaging effects of the β-amyloid (Aβ deposits in the brain. The activation of microglia may promote the neurodegenerative process through the release of proinflammatory cytokines, such as interleukin-1β (IL-1β and tumor necrosis factor-α (TNFα, which may lead to neuronal damage and eventual death. Aged garlic extract (AGE has been reported to have multiple biological activities, including anti-inflammatory effects. Therefore, the objective of this study was to investigate the effect of AGE on Aβ (1-42-induced cognitive dysfunction and neuroinflammation. Adult male Wistar rats were given AGE (125, 250, and 500 mg/kg BW, body weight, orally administered, daily for 56 days. They were then injected with 1 μL of aggregated Aβ (1-42 into the lateral ventricles; bilaterally. Seven days later, their recognition memory was evaluated using a novel object recognition (NOR test. Then the rats were sacrificed to investigate the alteration of microglia cells, IL-1β and TNFα in the cerebral cortex and hippocampus. The results indicated that AGE at doses of 250 and 500 mg/kg BW significantly improved short-term recognition memory in cognitively impaired rats. In addition, AGE significantly minimized the inflammatory response by reducing the activation of microglia and IL-1β to the levels found in the control, which is similar to the results found in Celebrex-treated rats. In conclusion, AGE may be useful for improving the short-term recognition memory and relieve the neuroinflammation in Aβ-induced rats.

  3. Neuroprotective Effects of Aged Garlic Extract on Cognitive Dysfunction and Neuroinflammation Induced by β-Amyloid in Rats

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    Nillert, Nutchareeporn; Pannangrong, Wanassanun; Welbat, Jariya Umka; Chaijaroonkhanarak, Wunnee; Sripanidkulchai, Kittisak; Sripanidkulchai, Bungorn

    2017-01-01

    Neuroinflammation is pathological evidence of Alzheimer’s disease (AD) that likely starts as a host defense response to the damaging effects of the β-amyloid (Aβ) deposits in the brain. The activation of microglia may promote the neurodegenerative process through the release of proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), which may lead to neuronal damage and eventual death. Aged garlic extract (AGE) has been reported to have multiple biological activities, including anti-inflammatory effects. Therefore, the objective of this study was to investigate the effect of AGE on Aβ (1-42)-induced cognitive dysfunction and neuroinflammation. Adult male Wistar rats were given AGE (125, 250, and 500 mg/kg BW, body weight), orally administered, daily for 56 days. They were then injected with 1 μL of aggregated Aβ (1-42) into the lateral ventricles; bilaterally. Seven days later, their recognition memory was evaluated using a novel object recognition (NOR) test. Then the rats were sacrificed to investigate the alteration of microglia cells, IL-1β and TNFα in the cerebral cortex and hippocampus. The results indicated that AGE at doses of 250 and 500 mg/kg BW significantly improved short-term recognition memory in cognitively impaired rats. In addition, AGE significantly minimized the inflammatory response by reducing the activation of microglia and IL-1β to the levels found in the control, which is similar to the results found in Celebrex-treated rats. In conclusion, AGE may be useful for improving the short-term recognition memory and relieve the neuroinflammation in Aβ-induced rats. PMID:28054940

  4. Reactive oxygen species scavenging activities in a chemiluminescence model and neuroprotection in rat pheochromocytoma cells by astaxanthin, beta-carotene, and canthaxanthin.

    Science.gov (United States)

    Chang, Chi-Sen; Chang, Chia-Lin; Lai, Guia-Hung

    2013-08-01

    The objective of this study was to determine chemiluminescence (CL) antioxidant activities and neuroprotective effects of astaxanthin, beta-carotene (β-carotene), and canthaxanthin on undifferentiated rat pheochromocytoma (PC12) cells. We performed three CL antioxidant assays, and the three carotenoids showed varying degrees of antioxidant activity, with astaxanthin exhibiting the highest antioxidant activity than the other two samples. Results of a pyrogallol-luminol assay revealed β-carotene to have higher antioxidant activity than canthaxanthin, whereas cupric sulfate-Phen-Vc-hydrogen peroxide (H₂O₂) assay showed canthaxanthin to have higher antioxidant activity than β-carotene. Luminol-H₂O₂ assay showed the antioxidant activity series as canthaxanthin > β-carotene at 62.5-1000 μg/mL and β-carotene > canthaxanthin at 1000-4000 μg/mL. Astaxanthin exhibited partial neuroprotective activity against H₂O₂ and the strongest neuroprotective activity against amyloid beta-peptide(25-35) [(Aβ)(25-35)]-induced undifferentiated PC12 cell deaths at 0.5-5.0 μM. Canthaxanthin showed partial neuroprotective activity in Aβ(25-35)-induced undifferentiated PC12 cell deaths at 1.0-5.0 μM. Astaxanthin protected undifferentiated PC12 cells from the damaging effects of H₂O₂ and Aβ(25-35) by the following ways: (1) scavenging superoxide anion radicals, hydroxyl radicals, and H₂O₂; (2) securing cell viability; (3) suppressing the production of reactive oxygen species; and (4) eliminating calcium ion influx. Our results conclusively show that astaxanthin has the merit as a potential neuron protectant.

  5. Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic rats.

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    El-Akabawy, Gehan; El-Kholy, Wael

    2014-05-01

    Diabetes mellitus results in neuronal damage caused by increased intracellular glucose leading to oxidative stress. Recent evidence revealed the potential of ginger for reducing diabetes-induced oxidative stress markers. The aim of this study is to investigate, for the first time, whether the antioxidant properties of ginger has beneficial effects on the structural brain damage associated with diabetes. We investigated the observable neurodegenerative changes in the frontal cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of ginger (500 mg/kg/day). Sections of frontal cortex, dentate gyrus, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, caspase-3, glial fibrillary acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our results revealed a protective role of ginger on the diabetic brain via reducing oxidative stress, apoptosis, and inflammation. In addition, this study revealed that the beneficial effect of ginger was also mediated by modulating the astroglial response to the injury, reducing AChE expression, and improving neurogenesis. These results represent a new insight into the beneficial effects of ginger on the structural alterations of diabetic brain and suggest that ginger might be a potential therapeutic strategy for the treatment of diabetic-induced damage in brain.

  6. The Neuroprotective Effect of Cornus mas on Brain Tissue of Wistar Rats

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    Renata Francik

    2014-01-01

    Full Text Available Cornelian cherry (Cornus mas is a valuable source of phenolic antioxidants. Flavonoid derivatives as nonenzymatic antioxidants are important in the pathophysiology of many diseases including neurological disorders (e.g., Alzheimer’s disease or heart disease. In this study, we examined the effect of an addition of freeze-dried fruit of cornelian cherry on three types of diets: control diet, fructose diet, and diet enriched in fats (high-fat diet. This effect was studied by determining the following antioxidant parameters in both brain tissue and plasma in rats: catalase, ferric reducing ability of plasma, paraoxonase, protein carbonyl groups, and free thiol groups. Results indicate that both fructose diet and high-fat diet affect the antioxidant capacity of the organism. Furthermore, an addition of cornelian cherry resulted in increased activity of catalase in brain tissue, while in plasma it caused the opposite effect. In turn, with regard to paraoxonase activity in both brain tissue and plasma, it had a stimulating effect. Adding cornelian cherry to the tested diets increased the activity of PON in both tested tissues. Moreover, protective effect of fruits of this plant was observed in the process of oxidation of proteins by decreasing levels of protein carbonyl groups and thiol groups in brain tissue as well as in plasma.

  7. Neuroprotective effect of epigallocatechin-3-gallate on hemisection-induced spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    Fengjun Deng; Rubing Li; Yingbao Yang; Dan Zhou; Qian Wang; Jiangping Xu

    2011-01-01

    Epigallocatechin-3-gallate (EGCG), a naturally occurring compound in green tea, has been widely used as an antioxidant agent. In the present study, model rats with acute spinal cord injury were intraperitoneally injected with 25, 50, and 100 mg/kg EGCG, and spinal cord ultrastructure, oxidative stress reaction, inflammatory factors, and apoptosis-associated gene expression were observed. Results showed that EGCG attenuated neuronal and axonal injury 24 hours post injury. It also decreased serum interleukin-1β, tumor necrosis factor-α, and intercellular adhesion molecule-1 release, and decreased apoptosis-associated gene expression. Furthermore, it increased the level of the superoxide anion (O2-), superoxide dismutase, and B-cell lymphoma/leukemia-2, and reduced malondialdehyde levels. Furthermore, it reduced the expression of the pro-apoptotic protein Bax. Noticeably, EGCG at the 100 mg/kg dosage exhibited similar effects as methylprednisolone sodium succinate, which has been frequently used for clinical acute spinal cord injury. The results demonstrated that EGCG can significantly inhibit inflammation, suppress oxidation, and reduce apoptosis in acute spinal cord injury.

  8. Neuroprotective effect of chondroitinase ABC on primary and secondary brain injury after stroke in hypertensive rats.

    Science.gov (United States)

    Chen, Xin-ran; Liao, Song-jie; Ye, Lan-xiang; Gong, Qiong; Ding, Qiao; Zeng, Jin-sheng; Yu, Jian

    2014-01-16

    Focal cerebral infarction causes secondary damage in the ipsilateral ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs) are a family of putative inhibitory components, and its degradation by chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study investigated the role of ChABC in the primary and secondary injury post stroke in hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), and were subjected to continuous intra-infarct infusion of ChABC (0.12 U/d for 7 days) 24 h later. Neurological function was evaluated by a modified neurologic severity score. Neurons were counted in the peri-infarct region and the ipsilateral VPN 8 and 14 days after MCAO by Nissl staining and NeuN labeling. The expressions of CSPGs, growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function. The study demonstrated that intra-infarct ChABC infusion could salvage the brain from both primary and secondary injury by the intervention on the neuroinhibitory environment post focal cerebral infarction.

  9. Neuroprotective Effects of Carnosic Acid in an Experimental Model of Alzheimer’s Disease in Rats

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    Mohammad Taghi Joghataie

    2011-01-01

    Full Text Available Objective: Alzheimer’s disease is the most common type of neurodegenerative disorder.It has been suggested that oxidative stress can be one of the pathological mechanisms ofthis disease. Carnosic acid (CA is an effective antioxidant substance and recent studieshave shown that its electrophilic compounds play a role in reversing oxidative stress. Thuswe tried to find out whether CA administration protects hippocampal neurons, preventingneurodegeneration in rats.Materials and Methods: Animals were divided into four groups: Sham-operated (sham,CA-pretreated sham-operated (sham+CA, untreated lesion (lesion and CA-pretreatedlesion (lesion+CA. Animals in all groups received vehicle or vehicle plus CA (CA: 10mg/kg intra-peritoneally one hour before surgery, again the same solution injected 3-4hours after surgery (CA: 3 mg/kg and repeated each afternoon for 12 days. A lesionwas made by bilateral intra-hippocampal injection of 4 μl of beta amyloid protein (1.5nmol/μl or vehicle in each side. 14 days after surgery, the brains were extracted forhistochemical studies. Data was expressed as mean ± SEM and analyzed using SPSSstatistical software.Results: Results showed that pretreatment with carnosic acid can reduce cellular deathin the cornu ammonis 1 (CA1 region of the hippocampus in the lesion+CA group, as comparedwith the lesion group.Conclusion: Carnosic acid may be useful in protecting against beta amyloid-induced neurodegenerationin the hippocampus.

  10. Spinal cord stimulation exerts neuroprotective effects against experimental Parkinson's disease.

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    Aiko Shinko

    Full Text Available In clinical practice, deep brain stimulation (DBS is effective for treatment of motor symptoms in Parkinson's disease (PD. However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS. We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz with an epidural electrode at C1-2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the

  11. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

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    Tayra Judith

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL staining. Results Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups. Conclusions Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

  12. Neuroprotective Effect of Total and Sequential Extract of Scrophularia striata Boiss. in Rat Cerebellar Granule Neurons Following Glutamate- Induced Neurotoxicity: An In-vitro Study

    Science.gov (United States)

    Salavati, Parvin; Ramezani, Mina; Monsef-Esfahani, Hamid R; Hajiagha, Reza; Parsa, Maliheh; Tavajohi, Shoreh; Ostad, Seyed Nasser

    2013-01-01

    Neuroprotective effect of the extract from aerial parts of Scrophularia striata Boiss (Scrophulariaceae) was investigated against glutamate-induced neurotoxicity on cultured rat pups Cerebellar Granule Neurons (CGNs). CGNs from 8 days old Sprague-Dawley rat were prepared and cultured. The experiments were performed after 8 days in culture. The plant was collected from the northeastern part (Ruin region) of Iran and air-dried at room temperature. The total extract was prepared with maceration of prepared powder in ethanol 80% for three times. Sequential extracts were obtained using dried and powdered aerial parts with increasingly polar solvents: petroleum ether, chloroform, ethyl acetate and methanol 80% solution. Cultured cells were exposed to 125 μM of glutamate for 12 h following a 24 h of incubation with test fractions at concentration of 10 mcg/mL. Morphological assay was performed using invert light microscope after fixation and staining with haematoxylin. Neuronal viability was measured using MTT assay. Statistical analysis was done using SPSS software. One way analysis of variance (ANOVA) was performed by Tukey post-hoc test. Values were considered statistically significant when p-value ≤ 0.05. Results of this study showed a significant neuroprotective activity of high polarity methanolic fraction of aerial parts of Scrophularia striata against glutamate-induced neurotoxicity in a dosedependent manner. Treatment with 10 mcg/mL of the fractions showed the best result. PMID:24250613

  13. Adolescent social isolation influences cognitive function in adult rats

    Institute of Scientific and Technical Information of China (English)

    Feng Shao; Xiao Han; Shuang Shao; Weiwen Wang

    2013-01-01

    Adolescence is a critical period for neurodevelopment. Evidence from animal studies suggests that isolated rearing can exert negative effects on behavioral and brain development. The present study aimed to investigate the effects of adolescent social isolation on latent inhibition and brain-derived neurotrophic factor levels in the forebrain of adult rats. Male Wistar rats were randomly divided into adolescent isolation (isolated housing, 38–51 days of age) and social groups. Latent inhibition was tested at adulthood. Brain-derived neurotrophic factor levels were measured in the medial prefrontal cortex and nucleus accumbens by an enzyme-linked immunosorbent assay. Adolescent social isolation impaired latent inhibition and increased brain-derived neurotrophic factor levels in the medial prefrontal cortex of young adult rats. These data suggest that adolescent social isolation has a profound effect on cognitive function and neurotrophin levels in adult rats and may be used as an animal model of neurodevelopmental disorders.

  14. Effect of 8 weeks Resistance Training on BDNF and TrkB in the Hippocampus of Adult Male Rats

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    S Mojtahedi

    2014-08-01

    Full Text Available Background & aim: Exercise enhances the synaptic plasticity and neuroprotective effects in the adult brain. However, it remains unknown that how plasticity molecules change following types of training. The purpose of this study was to determine the effect of eight weeks resistance training on protein levels of Brain Derived Neurotrophic Factor(BDNF and receptor of TrkB, in the hippocampus of adult male rats. Methods: In this experimental study, twelve adult male rats, 8 weeks of age, with an average weight of 200 to 225 grams were randomly divided into two groups, control and exercise respectively. The exercise was to increase the weight on the ladder. 24 hours after their last training session. The animals were killed and the hippocampus was removed for further testing. ELISA determined changes in protein levels. Data were analyzed by independent t test. Results: There was a significant difference between train and control groups In protein level of variables statically (p≤0.05. In addition, protein levels of BDNF and TrkB in the hippocampus of rats increased. Conclusion: Resistance training is beneficial for promoting hippocampal plasticity associated with BDNF signaling and consequently functional and cognitive benefits.

  15. Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson's disease: importance of antioxidant and cannabinoid receptor-independent properties.

    Science.gov (United States)

    García-Arencibia, Moisés; González, Sara; de Lago, Eva; Ramos, José A; Mechoulam, Raphael; Fernández-Ruiz, Javier

    2007-02-23

    We have recently demonstrated that two plant-derived cannabinoids, Delta9-tetrahydrocannabinol and cannabidiol (CBD), are neuroprotective in an animal model of Parkinson's disease (PD), presumably because of their antioxidant properties. To further explore this issue, we examined the neuroprotective effects of a series of cannabinoid-based compounds, with more selectivity for different elements of the cannabinoid signalling system, in rats with unilateral lesions of nigrostriatal dopaminergic neurons caused by local application of 6-hydroxydopamine. We used the CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA), the CB2 receptor agonist HU-308, the non-selective agonist WIN55,212-2, and the inhibitors of the endocannabinoid inactivation AM404 and UCM707, all of them administered i.p. Daily administration of ACEA or WIN55,212-2 did not reverse 6-hydroxydopamine-induced dopamine (DA) depletion in the lesioned side, whereas HU-308 produced a small recovery that supports a possible involvement of CB2 but not CB1 receptors. AM404 produced a marked recovery of 6-hydroxydopamine-induced DA depletion and tyrosine hydroxylase deficit in the lesioned side. Possibly, this is caused by the antioxidant properties of AM404, which are derived from the presence of a phenolic group in its structure, rather than by the capability of AM404 to block the endocannabinoid transporter, because UCM707, another transporter inhibitor devoid of antioxidant properties, did not produce the same effect. None of these effects were observed in non-lesioned contralateral structures. We also examined the timing for the effect of CBD to provide neuroprotection in this rat model of PD. We found that CBD, as expected, was able to recover 6-hydroxydopamine-induced DA depletion when it was administered immediately after the lesion, but it failed to do that when the treatment started 1 week later. In addition, the effect of CBD implied an upregulation of mRNA levels for Cu,Zn-superoxide dismutase

  16. Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice.

    Science.gov (United States)

    Ahmad, Ashfaq; Ali, Tahir; Park, Hyun Young; Badshah, Haroon; Rehman, Shafiq Ur; Kim, Myeong Ok

    2017-04-01

    Alzheimer's disease (AD) is a devastating and progressive neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau proteins in the brain. The deposition of Aβ aggregates triggers synaptic dysfunction, hyperphosphorylation of tau, and neurodegeneration, which lead to cognitive disorders. Here, we investigated the neuroprotective effect of fisetin in the Aβ1-42 mouse model of AD. Single intracerebroventricular injections of Aβ1-42 (3 μl/5 min/mouse) markedly induced memory/synaptic deficits, neuroinflammation, and neurodegeneration. Intraperitoneal injections of fisetin at a dose of 20 mg/kg/day for 2 weeks starting 24 h after Aβ1-42 injection significantly decreased the Aβ1-42-induced accumulation of Aβ, BACE-1 expression, and hyperphosphorylation of tau protein at serine 413. Fisetin treatment also markedly reversed Aβ1-42-induced synaptic dysfunction by increasing the levels of both presynaptic (SYN and SNAP-25) and postsynaptic proteins (PSD-95, SNAP-23, p-GluR1 (Ser 845), p-CREB (Ser 133) and p-CAMKII (Thr 286) and ultimately improved mouse memory, as observed in the Morris water maze test. Fisetin significantly activated p-PI3K, p-Akt (Ser 473), and p-GSK3β (Ser 9) expression in Aβ1-42-treated mice. Moreover, fisetin prevented neuroinflammation by suppressing various activated neuroinflammatory mediators and gliosis; it also suppressed the apoptotic neurodegeneration triggered by Aβ1-42 injections in the mouse hippocampus. Fluorojade-B and immunohistochemical staining for caspase-3 revealed that fisetin prevented neurodegeneration in Aβ1-42-treated mice. Our results suggest that fisetin has a potent neuroprotective effect against Aβ1-42-induced neurotoxicity. These results demonstrate that polyphenolic flavonoids such as fisetin could be a beneficial, effective and safe neuroprotective agent for preventing neurological disorders such as AD.

  17. In vivo evidence against clomethiazole being neuroprotective against MDMA ('ecstasy')-induced degeneration of rat brain 5-HT nerve terminals by a free radical scavenging mechanism.

    Science.gov (United States)

    Colado, M I; O'Shea, E; Esteban, B; Granados, R; Green, A R

    1999-02-01

    Clomethiazole is an effective neuroprotective agent against the degeneration of 5-HT neurones that follows administration of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy'). Since there is good evidence that free radical formation resulting from auto-oxidation of MDMA metabolites is responsible for the degeneration we have examined whether clomethiazole is a free radical scavenger. MDMA (15 mg/kg i.p.) increased the formation of 2,3- and 2,5-dihydroxybenzoic acids (2,3-DHBA and 2,5-DHBA) from salicylic acid perfused through a microdialysis tube implanted in the hippocampus, indicating increased free radical formation. Clomethiazole (50 mg/kg i.p.) administered 5 min prior and 55 min post MDMA prevented both the acute MDMA-induced hyperthermia and the rise in 2,3- and 2,5-DHBA. However, when the temperature of the MDMA + clomethiazole treated rats was kept elevated to that of the MDMA treated rats with a homeothermic blanket there was no inhibition of the MDMA-induced increase in 2,3-DHBA or 2,5-DHBA. These data suggest firstly that free radical formation is inhibited when the acute MDMA-induced hyperthermia is prevented. Secondly the data further indicate that clomethiazole has no free radical scavenging activity since the drug produces substantial neuroprotection when MDMA + clomethiazole treated rats are kept hyperthermic. This conclusion was strengthened by our observation that clomethiazole is a weak inhibitor (IC50 > 1 mM) of lipid peroxidation in synaptosomes when it had been induced by addition of FeCl2 + ascorbic acid.

  18. Approaches in methodology for population-based longitudinal study on neuroprotective model for healthy longevity (TUA) among Malaysian Older Adults.

    Science.gov (United States)

    Shahar, Suzana; Omar, Azahadi; Vanoh, Divya; Hamid, Tengku Aizan; Mukari, Siti Zamratol Mai-Sarah; Din, Normah Che; Rajab, Nor Fadilah; Mohammed, Zainora; Ibrahim, Rahimah; Loo, Won Hui; Meramat, Asheila; Kamaruddin, Mohd Zul Amin; Bagat, Mohamad Fazdillah; Razali, Rosdinom

    2016-12-01

    A number of longitudinal studies on aging have been designed to determine the predictors of healthy longevity, including the neuroprotective factors, however, relatively few studies included a wide range of factors and highlighted the challenges faced during data collection. Thus, the longitudinal study on neuroprotective model for healthy longevity (LRGS TUA) has been designed to prospectively investigate the magnitude of cognitive decline and its risk factors through a comprehensive multidimensional assessment comprising of biophysical health, auditory and visual function, nutrition and dietary pattern and psychosocial aspects. At baseline, subjects were interviewed for their status on sociodemographic, health, neuropsychological test, psychosocial and dietary intake. Subjects were also measured for anthropometric and physical function and fitness. Biospecimens including blood, buccal swap, hair and toenail were collected, processed and stored. A subsample was assessed for sensory function, i.e., vision and auditory. During follow-up, at 18 and 36 months, most of the measurements, along with morbidity and mortality outcomes will be collected. The description of mild cognitive impairment, successful aging and usual aging process is presented here. A total 2322 respondents were recruited in the data analysis at baseline. Most of the respondents were categorized as experiencing usual aging (73 %), followed by successful aging (11 %) and mild cognitive impairment (16 %). The LRGS TUA study is the most comprehensive longitudinal study on aging in Malaysia, and will contribute to the understanding of the aging process and factors associated with healthy aging and mental well-being of a multiethnic population in Malaysia.

  19. Hyperprolactinemia affects spermiogenesis in adult male rats.

    Science.gov (United States)

    Aleem, M; Choudhari, J; Padwal, V; Balasinor, N; Parte, P; Gill-Sharma, M K

    2005-01-01

    The mechanisms underlying the antifertility effects of hyperprolactinemia have yet to be established in an appropriate experimental model. Hyperprolactinemia is a known side effect of fluphenazine, a broad spectrum, long-acting phenothiazine known to be dopamine type-D2 receptor antagonist. In our earlier study in adult male rats, we reported that fluphenazine at a dose of 3 mg/kg/day suppressed serum FSH but not testosterone (T) through increasing dopamine (DA) metabolism in the pituitary gland, within 60 days. Fluphenazine treatment affected sperm quality and male rats treated with fluphenazine sired fewer litters. The effects of fluphenazine-induced hyperprolactinemia on sperm quality appeared to be related to reduced FSH. We now report that FSH suppression enhanced the uptake of acridine orange (AO), a DNA intercalating, fluorescent dye by the fluphenazine-treated caput epididymal sperms with concomitant reduction in the uptake of thiol-specific monobromobimane (mBBr) fluorescent dye in vitro, suggesting greater accessibility of DNA intercalating dye to sperm chromatin and reduction in free sperm protein thiols. The concomitant increase in AO and decrease in mBBr fluorescence was suggestive of loose chromatin packaging in caput epididymal sperms after treatment with fluphenazine at 3 mg/kg/day for 60 days. The suppression in levels of protamine (P1) in caput epididymal sperms suggested that chromatin hypocompaction was due to reduced deposition of protamines in sperm chromatin. Reduction in testicular levels of cyclic adenosyl 3', 5' monophosphate response element modulator (CREMtau) and P1 further suggested that reduced deposition was indeed due to reduced synthesis. The concomitant reduction in testicular levels of transition protein 1 (TP1) and transition protein 2 (TP2) also suggested that hypoprotamination was due to reduced synthesis of these proteins crucial for facilitating P1 deposition. The effect appeared to have occurred at the level of translation

  20. Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model.

    Science.gov (United States)

    Gao, Jingquan; Wang, Xuelai; Sun, Hongli; Cao, Yonggang; Liang, Shuang; Wang, Han; Wang, Yanming; Yang, Feng; Zhang, Fengyu; Wu, Lijie

    2016-04-01

    Prenatal exposure to valproic acid (VPA) in rat offspring is capable of inducing experimental autism with neurobehavioral aberrations. This study investigated the effect of docosahexaenoic acid (DHA) on hippocampal cell death, learning and memory alteration in an experimental rat autism model. We found that DHA supplementation (75, 150 or 300 mg/kg/day, 21 days) rescued the VPA (600 mg/kg) induced DHA reduction in plasma and hippocampus in a dose-dependent manner, increased the levels of hippocampal p-CaMKII and p-CREB without affecting total protein level, and altered BDNF-AKT-Bcl-2 signaling pathway, as well as inhibited the activity of caspase-3. DHA also influenced the content of malondialdehyde (MDA) and the activities of antioxidant enzymes in the VPA-treated offspring. Consistent with the previous results, we also observed that 300 mg/kg DHA supplementation markedly increased the cell survival, decreased the cell apoptosis, and increased mature neuronal cell in the hippocampus in VPA-treated offspring. Utilizing the Morris water maze test, we found that DHA prevented cognitive impairment in offspring of VPA-treated rats. The data suggested that DHA may play a neuroprotective role in hippocampal neuronal cell and ameliorates dysfunctions in learning and memory in this rat autism model. Thus, DHA could be used as treatment intervention for mitigating behavioral dysfunctions in autism spectrum disorder (ASD).

  1. Neuroprotective profile of enoxaparin, a low molecular weight heparin, in in vivo models of cerebral ischemia or traumatic brain injury in rats: a review.

    Science.gov (United States)

    Stutzmann, Jean-Marie; Mary, Veronique; Wahl, Florence; Grosjean-Piot, Odile; Uzan, André; Pratt, Jeremy

    2002-01-01

    The development of treatments for acute neurodegenerative diseases (stroke and brain trauma) has focused on (i) reestablishing blood flow to ischemic areas as quickly as possible (i.e. mainly antithrombotics or thrombolytics for stroke therapy) and (ii) on protecting neurons from cytotoxic events (i.e. neuroprotective therapies such as anti-excitotoxic or anti-inflammatory agents for stroke and neurotrauma therapies). This paper reviews the preclinical data for enoxaparin in in vivo models of ischemia and brain trauma in rats. Following a photothrombotic lesion in the rat, enoxaparin significantly reduced edema at 24 h after lesion when the treatment was started up to 18 h after insult. Enoxaparin was also tested after an ischemic insult using the transient middle cerebral artery occlusion (tMCAO) model in the rat. Enoxaparin, 2 x 1.5 mg/kg i.v., significantly reduced the lesion size and improved the neuroscore when the treatment was started up to 5 h after ischemia. Enoxaparin, administered at 5 h after insult, reduced cortical lesion size in a dose-dependent manner. In permanent MCAO, enoxaparin (5 and 24 h after insult) significantly reduced lesion size and improved neuroscore. A slight and reversible elevation of activated partial thromboplastin time (APTT) suggests that enoxaparin is neuroprotective at a non-hemorrhagic dose. Traumatic brain injury (TBI) is often accompanied by secondary ischemia due in part to edema-induced compression of blood vessels. When enoxaparin, at 0.5 mg/kg i.v. + 4 x 1 mg/kg s.c., was administered later than 30 h after TBI, it significantly reduced edema in hippocampus and parietal cortex. At one week after TBI the lesion size was significantly reduced and the neurological deficit significantly improved in enoxaparin treated animals. Finally, the cognitive impairment was significantly improved by enoxaparin at 48 h to 2 weeks after TBI. The anticoagulant properties of unfractionated heparin and specifically enoxaparin can explain

  2. Involvement of AMPA/kainate and GABAA receptors in topiramate neuroprotective effects against methylphenidate abuse sequels involving oxidative stress and inflammation in rat isolated hippocampus.

    Science.gov (United States)

    Motaghinejad, Majid; Motevalian, Manijeh

    2016-08-01

    Abuses of methylphenidate (MPH) as psychostimulant cause neural damage of brain cells. Neuroprotective properties of topiramate (TPM) have been indicated in several studies but its exact mechanism of action remains unclear. The current study evaluates protective role of various doses of TPM and its mechanism of action in MPH induced oxidative stress and inflammation. The neuroprotective effects of various doses of TPM against MPH induced oxidative stress and inflammation were evaluated and then the action of TPM was studied in presence of domoic acid (DOM), as AMPA/kainate receptor agonist and bicuculline (BIC) as GABAA receptor antagonist, in isolated rat hippocampus. Open Field Test (OFT) was used to investigate motor activity changes. Oxidative, antioxidant and inflammatory factors were measured in isolated hippocampus. TPM (70 and 100mg/kg) decreased MPH induced motor activity disturbances and inhibit MPH induced oxidative stress and inflammation. On the other hand pretreatment of animals with DOM or BIC, inhibit this effect of TPM and potentiate MPH induced motor activity disturbances and increased lipid peroxidation, mitochondrial oxidized form of glutathione (GSSG) level, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in isolated hippocampal cells and decreased reduced form of glutathione (GSH) level, superoxide dismutase, glutathione peroxidase and glutathione reductase activity. It seems that TPM can protect cells of hippocampus from oxidative stress and neuroinflammation and it could be partly by activation of GABAA receptor and inhibition of AMPA/kainite receptor.

  3. Neuroprotective Properties of a Standardized Extract from Myracrodruon urundeuva Fr. All. (Aroeira-Do-Sertão, as Evaluated by a Parkinson’s Disease Model in Rats

    Directory of Open Access Journals (Sweden)

    Iana Calou

    2014-01-01

    Full Text Available Myracrodruon urundeuva Fr. All. (Anacardiaceae is a Brazilian medicinal species, which is common to the Northeastern Brazilian semiarid region, whose stem-bark is widely used in folk medicine. It is an endangered species, presenting as main bioactive components tannins and chalcones. In this work, we studied the neuroprotective effects of a standardized extract from cultivated M. urundeuva (SEMU, in a model of Parkinson’s disease. Thus, a unilateral injection of 6-OHDA was done into the rat right stratum. The animals were submitted to stereotaxic surgery, then treated with SEMU (5, 10, 20, or 40 mg/kg, p.o. for 2 weeks, subjected to behavioral tests, and euthanized for striata dissections and neurochemical, histological, and immunohistochemical analyses. We showed, for the first time, that SEMU reverted behavioral alterations seen in the 6-OHDA-lesioned group and partially blocked the decrease in DA and DOPAC contents. The numbers of viable neurons and TH immunopositive cells were increased by SEMU. In addition, the SEMU-treated 6-OHDA groups showed lower numbers of GFAP and OX-42 immunopositive cells. The neuroprotective action of SEMU is possibly related to the antioxidant and anti-inflammatory properties of M. urundeuva, pointing out to its potential use in the prevention or treatment of neurodegenerative conditions, such as Parkinson’s disease.

  4. Dobutamine stress echocardiography in healthy adult male rats

    OpenAIRE

    Couet Jacques; Roussel Élise; Drolet Marie-Claude; Lachance Dominic; Plante Eric; Arsenault Marie

    2005-01-01

    Abstract Background Dobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response. Methods 15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intra...

  5. Hypertension after bilateral kidney irradiation in young and adult rats

    Energy Technology Data Exchange (ETDEWEB)

    Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

    1987-09-01

    The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension.

  6. OS 32-03 ANGIOTENSIN II TYPE 2 RECEPTOR AGONIST EXERTS SUSTAINED NEUROPROTECTIVE EFFECTS IN AGED RATS

    DEFF Research Database (Denmark)

    Sumners, Colin; Isenberg, Jacob; Harmel, Allison;

    2016-01-01

    OBJECTIVE: The renin angiotensin system is a promising target for stroke neuroprotection and therapy through activation of angiotensin type II receptors (AT2R). The selective non-peptide AT2R agonist, Compound 21 (C21), has been shown to exhibit neuroprotection and improve stroke outcomes...... min), 24 h, and 48 h after stroke. Infarct size was assessed by magnetic resonance imaging at 21 days post MCAO. Animals received blinded neurological exams at 4 h, 24 h, 72 h, 7d, 14d, and 21d post-MCAO. RESULTS: Systemic treatment with C21 after stroke significantly improved neurological function...

  7. Relationship with spatial memory in diabetic rats and protein kinase Cγ,caveolin-1 in the hippocampus and neuroprotective effect of catalpol

    Institute of Scientific and Technical Information of China (English)

    Zhou Haicheng; Liu Jing; Ren Liyuan; Liu Wei; Xing Qian; Men Lili; Song Guirong

    2014-01-01

    Background The mechanisms underlying diabetic encephalopathy are largely unknown,and no effective treatments are available.Catalpol has received much attention due to its numerous biological effects,especially in neuroprotective studies.The aim of this study was to investigate the effects of catalpol on cognitive functions in diabetic rats and the underlying mechanisms.Methods A rat model of diabetes was established by streptozotocin injection,followed by intraperitoneal infusion of catalpol after 10 weeks.Two weeks later,the Morris water maze was used to test the spatial learning performance.Nissl staining was performed to evaluate the morphological changes in the hippocampus.Expression of protein kinase Cy (PKCy) and caveolin-1 (Cav-1) in the hippocampus were assessed by reverse transcription PCR and Western blotting.Activities of anti-oxidative enzymes such as glutathione (GSH),superoxide dismutase (SOD) and catalase (CAT) and levels of malonaldehyde (MDA) were measured using commercial kits.Results Significant hippocampal neuronal injury was observed in rats with streptozotocin-induced diabetes.Moreover,cognitive dysfunction was associated with markedly increased oxidative stress in the brain.Catalpol treatment significantly attenuated cognitive deficits,neuronal damage,and oxidative stress in the brain of diabetic rats.Biochemical analyses showed that catalpol reversed the down-regulation of PKCγ and Cav-1 expression in the diabetic rats.Conclusions Spatial memory in diabetic rats is associated with the expression of PKCy and Cav-1.Catalpol treatment markedly attenuated oxidative stress,reversed the alteration of PKCy,Cav-1 and spatial memory deficits.

  8. Downstream signaling of reactive oxygen species, protein kinase C epsilon translocation and delayed neuroprotection in sevoflurane preconditioned rats following cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Zhi Ye; Qulian Guo; E Wang; Yundan Pan; Qing Li; Honghao Zhou

    2009-01-01

    BACKGROUND: Brief exposure to the anesthetic sevoflurane results in delayed neuroprotection.However, few studies have addressed delayed neuroprotection after preconditioning with a single administration of sevoflurane.OBJECTIVE: To explore the relationship between a single preconditioning administration of sevoflurane and reactive oxygen species production and protein kinase C-epsilon (PKC- ε ) translocation.DESIGN, TIME, AND SETTING: The randomized, controlled, animal experiment was conducted at the Central Laboratory, Xiangya Hospital, Central South University, China from November 2007 to April 2008.MATERIALS: A total of 120 healthy, male, Sprague Dawley rats were equally and randomly assigned into five groups: sham operation, ischemia/reperfusion, sevoflurane, 2-mercaptopropionylglycine (2-MPG, a selective reactive oxygen species scavenger) + sevoflurane (MPG + sevoflurane), and MPG. Sevoflurane (Baxter, USA) and MPG (Sigma, USA) were used in this study.METHODS: Intervention consisted of three procedures. (1) MPG injection: a selective reactive oxygen species scavenger, MPG (20 mg/kg), was infused into the rat caudal vein in the MPG and MPG + sevoflurane groups. (2) Sevoflurane preconditioning: 30 minutes following MPG injection,rats in the sevoflurane and MPG + sevoflurane groups breathed a mixed gas of 2.4% sevoflurane and 97.6% oxygen for 60 minutes. Rats in the sham operation, ischemia/reperfusion, and MPG groups breathed 100% pure oxygen for 60 minutes. (3) Ischemia/reperfusion: 24 hours after sevoflurane or pure oxygen preconditioning, middle cerebral artery occlusion models were established in the ischemia/reperfusion, sevoflurane, MPG + sevoflurane, and MPG groups.Following 2 hours ischemia/6 hours and 24 hours reperfusion, the carotid artery was separated, but the middle cerebral artery was not occluded, in the sham operation group.MAIN OUTCOME MEASURES: In the ischemic hemisphere, PKC-ε translocation in the rat parietal cortex was measured by Western

  9. L-PGDS Mediates Vagus Nerve Stimulation-Induced Neuroprotection in a Rat Model of Ischemic Stroke by Suppressing the Apoptotic Response.

    Science.gov (United States)

    Zhang, Lina; Ma, Jingxi; Jin, Xinhao; Jia, Gongwei; Jiang, Ying; Li, Changqing

    2017-02-01

    The role of lipocalin prostaglandin D2 synthase (L-PGDS) in brain ischemia has not been fully clarified to date. Vagus nerve stimulation (VNS) protects against cerebral ischemia/reperfusion (I/R) injury, but the mechanisms involved need further exploration. This study investigated the role of L-PGDS in cerebral I/R and whether this process was involved in the mechanism of VNS-mediated neuroprotection. Male Sprague-Dawley rats were pretreated with a lentiviral vector (LV) through intracerebroventricular injection, followed by middle cerebral artery occlusion (MCAO) and VNS treatment. The expression of L-PGDS in the peri-infarct cortex was examined. The localization of L-PGDS was determined using double immunofluorescence staining. Neurologic scores, infarct volume and neuronal apoptosis were evaluated at 24 h after reperfusion. The expression of apoptosis-related molecules was measured by western blot analysis. The expression of L-PGDS in the peri-infarct cortex increased at 12 h, reached a peak at 24 h after reperfusion, and lasted up to 3 days. VNS treatment further enhanced the expression of L-PGDS following ischemic stroke. L-PGDS was mainly expressed in neurons in the peri-infarct cortex. I/R rats treated with VNS showed better neurological deficit scores, reduced infarct volume, and decreased neuronal apoptosis as indicated by the decreased levels of Bax and cleaved caspase-3 as well as increased levels of Bcl-2. Strikingly, the beneficial effects of VNS were weakened after L-PGDS down-regulation. In general, our results suggest that L-PGDS is a potential mediator of VNS-induced neuroprotection against I/R injury.

  10. Neuro-protective potential of a vesicular system of a standardized extract of a new chemotype of Withania somnifera Dunal (NMITLI118RT+) against cerebral stroke in rats().

    Science.gov (United States)

    Ahmad, Hafsa; Khandelwal, Kiran; Samuel, Sheeba Saji; Tripathi, Shivangi; Mitra, Kalyan; Sangwan, Rajender Singh; Shukla, Rakesh; Dwivedi, Anil Kumar

    2016-09-01

    Withania somnifera Dunal is an Indian medicinal plant with significant pharmacological properties, such as adaptogenic, anti-inflammatory, anti-oxidant, anti-platelet, anti-hypertensive, hypoglycemic and hypolipidemic effects. Several chemotypes of W. somnifera include NMITLI-101, NMITLI-118 and NMITLI-128. The present work elaborates the optimization and development of a liposomal delivery system for efficient delivery of NMITLI118RT+ [a standardized ethanolic extract of a new chemotype of W. somnifera Dunal (NMITLI-118) roots] against cerebral stroke in rats. Liposomal systems were prepared using thin-film hydration method and characterized on the basis of size, zeta potential, physical stability, FT-IR, DSC-TGA analysis and surface morphological studies by TEM. NMITLI118RT+ and its formulations (NMITLI118RT+LF) were evaluated for biological activity utilizing middle cerebral artery occlusion model in rats. The Z average of the developed liposomal formulation was about 142.6 ± 0.09 nm with a zeta potential of -31.20 ± 1.0 mV. Results of TEM revealed spherical particles in the range of 200 nm. The entrapment efficiency was found to be 94.603 ± 2%. The formulation was found to be physically stable over a 3-week period. Results were suggestive of the fact that both NMITLI118RT+ and its delivery system possess significant neuroprotective activity in cerebral ischemia. The liposomal system largely exhibits better performance over NMITLI118RT+ precisely in the post-treatment group. The present studies could elucidate the successful development of a delivery system for NMITLI118RT+ and demonstrate their beneficial neuro-protective potential in overcoming and reversing the consequences of I/R injury following stroke.

  11. Repeated febrile convulsions impair hippocampal neurons and cause synaptic damage in immature rats:neuroprotective effect of fructose-1,6-diphosphate

    Institute of Scientific and Technical Information of China (English)

    Jianping Zhou; Fan Wang; Jun Zhang; Hui Gao; Yufeng Yang; Rongguo Fu

    2014-01-01

    Fructose-1,6-diphosphate is a metabolic intermediate that promotes cell metabolism. We hy-pothesize that fructose-1,6-diphosphate can protect against neuronal damage induced by febrile convulsions. Hot-water bathing was used to establish a repetitive febrile convulsion model in rats aged 21 days, equivalent to 3-5 years in humans. Ninety minutes before each seizure induc-tion, rats received an intraperitoneal injection of low- or high-dose fructose-1,6-diphosphate (500 or 1,000 mg/kg, respectively). Low- and high-dose fructose-1,6-diphosphate prolonged the latency and shortened the duration of seizures. Furthermore, high-dose fructose-1,6-di-phosphate effectively reduced seizure severity. Transmission electron microscopy revealed that 24 hours after the last seizure, high-dose fructose-1,6-diphosphate reduced mitochondrial swelling, rough endoplasmic reticulum degranulation, Golgi dilation and synaptic cleft size, and increased synaptic active zone length, postsynaptic density thickness, and synaptic interface cur-vature in the hippocampal CA1 area. The present findings suggest that fructose-1,6-diphosphate is a neuroprotectant against hippocampal neuron and synapse damage induced by repeated fe-brile convulsion in immature rats.

  12. Neuroprotective antioxidants from marijuana.

    Science.gov (United States)

    Hampson, A J; Grimaldi, M; Lolic, M; Wink, D; Rosenthal, R; Axelrod, J

    2000-01-01

    Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron cultures exposed to toxic levels of the neurotransmitter, glutamate. The psychotropic cannabinoid receptor agonist delta 9-tetrahydrocannabinol (THC) and cannabidiol, (a non-psychoactive constituent of marijuana), both reduced NMDA, AMPA and kainate receptor mediated neurotoxicities. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a (cannabinoid) receptor-independent mechanism of action. Glutamate toxicity can be reduced by antioxidants. Using cyclic voltametry and a fenton reaction based system, it was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants. As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons. In a head to head trial of the abilities of various antioxidants to prevent glutamate toxicity, cannabidiol was superior to both alpha-tocopherol and ascorbate in protective capacity. Recent preliminary studies in a rat model of focal cerebral ischemia suggest that cannabidiol may be at least as effective in vivo as seen in these in vitro studies.

  13. Influx mechanisms in the embryonic and adult rat choroid plexus

    DEFF Research Database (Denmark)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and a...

  14. Neuroprotective effects of stearic acid against toxicity of oxygen/glucose deprivation or glutamate on rat cortical or hippocampal slices

    Institute of Scientific and Technical Information of China (English)

    Ze-jian WANG; Guang-mei LI; Wen-lu TANG; Ming YIN

    2006-01-01

    Aim: To observe the effects of stearic acid, a long-chain saturated fatty acid consisting of 18 carbon atoms, on brain (cortical or hippocampal) slices insulted by oxygen-glucose deprivation (OGD), glutamate or sodium azide (NaN3) in vitro.Methods: The activities of hippocampal slices were monitored by population spikes recorded in the CA1 region. In vitro injury models of brain slice were induced by 10 min of OGD, 1 mmol/L glutamate or 10 mmol/L NaN3. After 30 min of preincubation with stearic acid (3-30 μmol/L), brain slices (cortical or hippocampal)were subjected to OGD, glutamate or NaN3, and the tissue activities were evaluated by using the 2,3,5-triphenyltetrazolium chloride method. MK886 [5 mmol/L;a noncompetitive inhibitor of proliferator-activated receptor (PPAR-α)] or BADGE (bisphenol A diglycidyl ether; 100 μmol/L; an antagonist of PPAR-γ) were tested for their effects on the neuroprotection afforded by stearic acid. Results: Viability of brain slices was not changed significantly after direct incubation with stearic acid. OGD, glutamate and NaN3 injury significantly decreased the viability of brain slices. Stearic acid (3-30 μmol/L) dose-dependently protected brain slices from OGD and glutamate injury but not from NaN3 injury, and its neuroprotective effect was completely abolished by BADGE. Conclusion: Stearic acid can protect brain slices (cortical or hippocampal) against injury induced by OGD or glutamate.Its neuroprotective effect may be mainly mediated by the activation of PPAR-γ.

  15. Fractalkine and CX3CR1 regulate hippocampal neurogenesis in adult and aged rats

    Science.gov (United States)

    Bachstetter, Adam D.; Morganti, Josh M.; Jernberg, Jennifer; Schlunk, Andrea; Mitchell, Staten H.; Brewster, Kaelin W.; Hudson, Charles E.; Cole, Michael J; Harrison, Jeffrey K.; Bickford, Paula C.; Gemma, Carmelina

    2010-01-01

    Microglia have neuroprotective capacities, yet chronic activation can promote neurotoxic inflammation. Neuronal fractalkine (FKN), acting on CX3CR1, has been shown to suppress excessive microglia activation. We found that disruption in FKN/ CX3CR1 signaling in young adult rodents decreased survival and proliferation of neural progenitor cells through IL-1β. Aged rats were found to have decreased levels of hippocampal FKN protein; moreover, interruption of CX3CR1 function in these animals did not affect neurogenesis. The age-related loss of FKN could be restored by exogenous FKN reversing the age-related decrease in hippocampal neurogenesis. There were no measureable changes in young animals by the addition of exogenous FKN. The results suggest that FKN/ CX3CR1 signaling has a regulatory role in modulating hippocampal neurogenesis via mechanisms that involve indirect modification of the niche environment. As elevated neuroinflammation is associated with many age-related neurodegenerative diseases, enhancing FKN/ CX3CR1 interactions could provide an alternative therapeutic approach to slow age-related neurodegeneration. PMID:20018408

  16. Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke.

    Science.gov (United States)

    Duricki, Denise A; Hutson, Thomas H; Kathe, Claudia; Soleman, Sara; Gonzalez-Carter, Daniel; Petruska, Jeffrey C; Shine, H David; Chen, Qin; Wood, Tobias C; Bernanos, Michel; Cash, Diana; Williams, Steven C R; Gage, Fred H; Moon, Lawrence D F

    2016-01-01

    There is an urgent need for a therapy that reverses disability after stroke when initiated in a time frame suitable for the majority of new victims. We show here that intramuscular delivery of neurotrophin-3 (NT3, encoded by NTF3) can induce sensorimotor recovery when treatment is initiated 24 h after stroke. Specifically, in two randomized, blinded preclinical trials, we show improved sensory and locomotor function in adult (6 months) and elderly (18 months) rats treated 24 h following cortical ischaemic stroke with human NT3 delivered using a clinically approved serotype of adeno-associated viral vector (AAV1). Importantly, AAV1-hNT3 was given in a clinically-feasible timeframe using a straightforward, targeted route (injections into disabled forelimb muscles). Magnetic resonance imaging and histology showed that recovery was not due to neuroprotection, as expected given the delayed treatment. Rather, treatment caused corticospinal axons from the less affected hemisphere to sprout in the spinal cord. This treatment is the first gene therapy that reverses disability after stroke when administered intramuscularly in an elderly body. Importantly, phase I and II clinical trials by others show that repeated, peripherally administered high doses of recombinant NT3 are safe and well tolerated in humans with other conditions. This paves the way for NT3 as a therapy for stroke.

  17. Ultrasonic Vocalizations by Adult Rats (Rattus norvegicus)

    Science.gov (United States)

    1991-12-01

    begun. Diazepam , chlordiazepoxide , morphine, or naloxone was administered I.P. prior to placing the rat in the tailshock apparatus. Four different...by chlordiazepoxide and diazepam . Drug Dev. Res., 5, 185-193 (1985). Gardner, C.R., and Budhram, P. Effects of agents which interact with central... diazepam , and chlorpromazine, attenuate these vocalizations. Recent work by Kaltwasser (1990) examined the occurrence of vocalizations in response to

  18. Implantable porous gelatin microspheres sustained release of bFGF and improved its neuroprotective effect on rats after spinal cord injury

    Science.gov (United States)

    ZhuGe, Qi-Chuan; Shen, Bi-Xin; Jin, Bing-Hui; Huang, Jian-Ping; Wu, Ming-Ze; Fan, Lu-Xin; Zhao, Ying-Zheng; Xu, He-Lin

    2017-01-01

    In this study, porous gelatin microspheres (GMSs) were constructed to improve the neuroprotective effect of basic fibroblast growth factor (bFGF) on spinal cord injury. GMSs were prepared by a W/O emulsion template, followed by cross-linking, washing and drying. The particle sizes and surface porosity of the blank GMSs were carefully characterized by scan electronic microscopy. The blank GMSs have a mean particle size of 35μm and theirs surface was coarse and porous. bFGF was easily encapsulated inside the bulk GMSs through diffusion along the porous channel. 200μg of bFGF was completely encapsulated in 100mg of GMSs. The bFGF-loaded GMSs displayed a continuous drug release pattern without an obvious burst release over two weeks in vitro. Moreover, the therapeutic effects of bFGF-loaded GMSs were also evaluated in spinal cord injury rat model. After implantation of bFGF-loaded GMSs, the recovery of the motor function of SCI rats were evaluated by behavioral score and foot print experiment. The motor function of SCI rats treated with bFGF-loaded GMSs was more obvious than that treated with free bFGF solution (P<0.05). At the 28th days after treatment, rats were sacrificed and the injured spinal were removed for histopathological and apoptosis examination. Compared with treatment with free bFGF solution, treatment with bFGF-loaded GMSs resulted in a less necrosis, less infiltration of leukocytes, and a reduced the cavity ratio and less apoptotic cells in injured spinal(P<0.01), indicating its better therapeutic effect. Implantable porous GMSs may be a potential carrier to deliver bFGF for therapy of spinal cord injury. PMID:28291798

  19. Neuroprotective effect of WIN55,212-2 against 3-nitropropionic acid-induced toxicity in the rat brain: involvement of CB1 and NMDA receptors

    Science.gov (United States)

    Maya-López, Marisol; Colín-González, Ana Laura; Aguilera, Gabriela; de Lima, María Eduarda; Colpo-Ceolin, Ana; Rangel-López, Edgar; Villeda-Hernández, Juana; Rembao-Bojórquez, Daniel; Túnez, Isaac; Luna-López, Armando; Lazzarini-Lechuga, Roberto; González-Puertos, Viridiana Yazmín; Posadas-Rodríguez, Pedro; Silva-Palacios, Alejandro; Königsberg, Mina; Santamaría, Abel

    2017-01-01

    The endocannabinoid system (ECS), and agonists acting on cannabinoid receptors (CBr), are known to regulate several physiological events in the brain, including modulatory actions on excitatory events probably through N-methyl-D-aspartate receptor (NMDAr) activity. Actually, CBr agonists can be neuroprotective. The synthetic CBr agonist WIN55,212-2 acts mainly on CB1 receptor. In turn, the mitochondrial toxin 3-nitropropionic acid (3-NP) produces striatal alterations in rats similar to those observed in the brain of Huntington’s disease patients. Herein, the effects of WIN55,212-2 were tested on different endpoints of the 3-NP-induced toxicity in rat brain synaptosomes and striatal tissue. Motor activity was also evaluated. The 3-NP (1 mM)-induced mitochondrial dysfunction and lipid peroxidation was attenuated by WIN55,212-2 (1 µM) in synaptosomal fractions. The intrastriatal bilateral injection of 3-NP (500 nmol/µL) to rats increased lipid peroxidation and locomotor activity, augmented the rate of cell damage, and decreased the striatal density of neuronal cells. These alterations were accompanied by transcriptional changes in the NMDA (NR1 subunit) content. The administration of WIN55212-2 (1 mg/kg, i.p.) to rats for six consecutive days, before the 3-NP injection, exerted preventive effects on all alterations elicited by the toxin. The prevention of the 3-NP-induced NR1 transcriptional alterations by the CBr agonist together with the increase of CB1 content suggest an early reduction of the excitotoxic process via CBr activation. Our results demonstrate a protective role of WIN55,212-2 on the 3-NP-induced striatal neurotoxicity that could be partially related to the ECS stimulation and induction of NMDAr hypofunction, representing an effective therapeutic strategy at the experimental level for further studies.

  20. Neuroprotective effects of nimodipine and MK-801 on acute infectious brain edema induced by injection of pertussis bacilli to neocortex of rats

    Institute of Scientific and Technical Information of China (English)

    陈立华; 刘丽旭; 杨于嘉; 刘运生; 曹美鸿

    2003-01-01

    Objective: To explore the mechanism and type of acute infectious brain edema induced by injection of pertussis bacilli (PB) in rat neocortex, to study the neuroprotective effect of non-competitive antagonist of N-methl-D-aspartate ( NMDA ) receptor ( MK-801 ) and antagonist of Ca2+ channels ( nimodipine )on brain edema, and to investigate the relationship between percentage of water content and cytosolic free calcium concentration ([Ca2+]i) in synaptosomes or content of Evans Blue (EB).Methods: 95 SD rats were randomly divided into five groups, ie, normal control group, sham-operated control group, PB group, nimodipine treatment group and MK-801 pretreatment group. The acute infectious brain edema was induced by injection of PB into the rats. Quantitative measurements of water content and the concentration of EB were performed. [Ca2+]i was determined in calcium fluorescent indication Fura-2/AM loaded neuronal synaptosome with a spectrofluorophotometer. To observe the effect of MK-801 and nimodipine, we administered MK-801 48 hours and 24 hours before the injection of PB in MK-801 pretreatment group, and nimodipine after the injection of PB in nimodipine treatment group. The specific binding of NMDA receptor was measured with [3H]-MK-801 in the neuronal membrane of cerebral cortex. Results: The levels of water content and EB content of brain tissues, and [Ca2+]i in the neuronal synaptosomes increased more significantly in the PB-injected cerebral hemisphere in the PB group than those of normal control group and sham-operated control group (P0.05). Conclusions: The changes in the permeability of blood-brain barrier (BBB) and Ca2+-overload may participate in the pathogenesis of infectious brain edema. Treatment with nimodipine can dramatically reduce the damage of brain edema and demonstrate neuroprotective effect on brain edema by inhibiting the excess of Ca2+ influx and reducing the permeability of BBB. MK-801 pretreatment may inhibit the delayed Ca2+ influx into

  1. Distribution of radiolabeled L-glutamate and D-aspartate from blood into peripheral tissues in naive rats: Significance for brain neuroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Klin, Yael [Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100 (Israel); Zlotnik, Alexander; Boyko, Matthew; Ohayon, Sharon; Shapira, Yoram [The Division of Anesthesiology, Soroka Medical Center and Ben Gurion University of the Negev, Beer-Sheva (Israel); Teichberg, Vivian I., E-mail: Vivian.teichberg@weizmann.ac.il [Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100 (Israel)

    2010-09-03

    Research highlights: {yields} Blood glutamate has a half-life time of 2-3 min. {yields} Blood glutamate is submitted to rapid decarboxylation. {yields} Blood glutamate and its metabolites are mainly absorbed in skeletal muscle and liver. {yields} The skeletal muscle and liver are now targets for potential drugs affording brain neuroprotection. -- Abstract: Excess L-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either L-[1-{sup 14}C] Glutamic acid (L-[1-{sup 14}C] Glu), L-[G-{sup 3}H] Glutamic acid (L-[G-{sup 3}H] Glu) or D-[2,3-{sup 3}H] Aspartic acid (D-[2,3-{sup 3}H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with L-[1-{sup 14}C] Glu and L-[G-{sup 3}H] Glu was faster than that associated with glutamate non-metabolized analog, D-[2,3-{sup 3}H] Asp. L-[1-{sup 14}C] Glu was subjected in blood to a rapid decarboxylation with the loss of {sup 14}CO{sub 2}. The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total L-[U-{sup 14}C] Glu or D-[2,3-{sup 3}H] Asp radioactivity capture. L-[U-{sup 14}C] Glu and D-[2,3-{sup 3}H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues

  2. Dietary supplementation with tBHQ, an Nrf2 stabilizer molecule, confers neuroprotection against apoptosis in amyloid β-injected rat.

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    Nouhi, Fatemeh; Tusi, Solaleh Khoramian; Abdi, Azadeh; Khodagholi, Fariba

    2011-05-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates the up-regulation of cytoprotective genes via the antioxidant response element (ARE). There is significant evidence that oxidative stress is a critical event in the pathogenesis of AD. Considering the protective role of Nrf2 against oxidative injury, we studied to determine whether in vivo toxicity of amyloid β (Aβ) can be attenuated by tBHQ, an Nrf2 stabilizer, Using an Aβ injection model. We demonstrated that pre-activation of endogenous Nrf2 by tBHQ attenuated Aβ-induced caspase-3 expression. tBHQ enhanced GSH, decreased MDA level, and inhibited NF-κB. This investigation provides the first documentation of tBHQ's neuroprotective effect through decrease of Aβ accumulation in rat brain. Our results show the involvement of Hsp-70 in this protective effect. In summary tBHQ treatment for 1 week prior to Aβ injection protected against the oxidative damage, apoptosis and Aβ accumulation in rats.

  3. A novel dual-glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor agonist is neuroprotective in transient focal cerebral ischemia in the rat.

    Science.gov (United States)

    Han, Ling; Hölscher, Christian; Xue, Guo-Fang; Li, Guanglai; Li, Dongfang

    2016-01-06

    Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have been shown to be neuroprotective in previous studies in animal models of Alzheimer's or Parkinson's disease. Recently, novel dual-GLP-1/GIP receptor agonists that activate both receptors (DA) were developed to treat diabetes. We tested the protective effects of a novel potent DA against middle cerebral artery occlusion injury in rats and compared it with a potent GLP-1 analog, Val(8)-GLP-1(glu-PAL). Animals were evaluated for neurologic deficit score, infarct volume, and immunohistochemical analyses of the brain at several time points after ischemia. The Val(8)-GLP-1(glu-PAL)-treated and DA-treated groups showed significantly reduced scores of neurological dysfunction, cerebral infarction size, and percentage of TUNEL-positive apoptotic neurons. Furthermore, the expression of the apoptosis marker Bax, the inflammation marker iNOS, and the survival marker Bcl-2 was significantly increased. The DA-treated group was better protected against neurodegeneration than the Val(8)-GLP-1(glu-PAL) group, and the scores of neurological dysfunction, cerebral infarction size, and expression of Bcl-2 were higher, whereas the percentage of TUNEL-positive neurons and the levels of Bax and iNOS were lower in the DA group. DA treatment reduced the infarct volume and improved the functional deficit. It also suppressed the inflammatory response and cell apoptosis after reperfusion. In conclusion, the novel GIP and GLP-1 dual-receptor agonist is more neuroprotective than a GLP-1 receptor agonist in key biomarkers of neuronal degeneration.

  4. The Neuroprotective Effect of Alcoholic Extract of Cannabis Sativa on Neuronal Density of Spinal Cord Alpha Motoneurons after Sciatic Nerve Injury in Rats

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    M Tehranipour

    2011-07-01

    Full Text Available Introduction: Injuries of the peripheral nerve system affect the neurons cell body leading to axon injury. Cannabis sativa plant has anti oxidant and anti apoptotic effects. Therefore the aim of present study was to study the neuroprotective effect of alcoholic extract of cannabis sativa leaves on neuronal density of alpha motoneurons in spinal cord after sciatic nerve injury in rats. Methods: In this experimental research, animals were divided into four groups; A: control, B: compression, C: compression+ treatment with 25 mg/kg alcoholic extract, D: compression + treatment with 50 mg/kg extract (n=8. At first, sciatic nerve compression in B, C and D groups was achieved for 60 seconds using locker pincers. Alcoholic extract was injected intra peritoneally in the first and second weeks after compression. Then 28 days after compression, under profusion method, the lumbar spinal cord was sampled and the numerical density in each group was compared with the compression group. The data was analyzed with the use of Minitab 14 software and ANOVA statistical test. Results: Neuronal density showed a meaningful difference in the compression and control groups(P<0.001. Neuronal density in treatment groups(25, 50 mg/kg also had a meaningful increase(P<0.001 as compared to the compression group. Conclusion: Alcoholic extract of cannabis sativa leaves has a neuroprotective effect on spinal cord alpha motoneurons after injury. This could be due to growth and regeneration factors present in the alcoholic extract of cannabis sativa leaves that induce regeneration process in injured neurons or prevent degeneration.

  5. Neuroprotective effects of prostaglandin A1 and its effect on IKK/IkB/NF-kB/c-myc signaling pathway in rat models of permanent focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Hui-lingZHANG; Zhen-lunGU; Zheng-hongQIN

    2005-01-01

    AIM Prostaglandin A1(PGA1) is a cyclopentenone prostaglandin. Recently, we reported that PGA1 can inhibit excitotoxin-induced apoptosis of striatal neurons in vivo and rotenone-induced apoptosis ofcultured SH-SY5Y cells, suggesting that PGA1 may have neuroprotective efficacy, possibly mediated by inhibition of NF-kB activation. The present study evaluated the neuroprotective potential of PGA1 and its effect on IKK/I( B/NF-kB/c-myc signaling pathway in rat models of permanent focal cerebral ischemia. METHODS Permanent middle cerebral artery occlusion (pMCAO) model was constructed by intraluminal suture cannulation through the internal carotid artery in Wistar rats.

  6. Gender-Dependent Effects of Enriched Environment and Social Isolation in Ischemic Retinal Lesion in Adult Rats

    Science.gov (United States)

    Kiss, Peter; Szabadfi, Krisztina; Horvath, Gabor; Tamas, Andrea; Farkas, Jozsef; Gabriel, Robert; Reglodi, Dora

    2013-01-01

    Exposure to an enriched environment has been shown to have many positive effects on brain structure and function. Numerous studies have proven that enriched environment can reduce the lesion induced by toxic and traumatic injuries. Impoverished environment, on the other hand, can have deleterious effects on the outcome of neuronal injuries. We have previously shown that enriched conditions have protective effects in retinal injury in newborn rats. It is well-known that the efficacy of neuroprotective strategies can depend on age and gender. The aim of the present study, therefore, was to examine the effects of environmental enrichment and social isolation in retinal ischemia. We used bilateral common carotid artery occlusion to induce retinal hypoperfusion in adult Wistar rats of both genders. Groups were housed in standard, enriched or impoverished conditions. Impoverished environment was induced by social isolation. Retinas were processed for histological analysis after two weeks of survival. In the present study, we show that (1) enriched environment has protective effects in adult ischemic retinal lesion, while (2) impoverished environment further increases the degree of ischemic injury, and (3) that these environmental effects are gender-dependent: females are less responsive to the positive effects of environmental enrichment and more vulnerable to retinal ischemia in social isolation. In summary, our present study shows that the effects of both positive and negative environmental stimuli are gender-dependent in ischemic retinal lesions. PMID:23921682

  7. Combining neuroprotectants in a model of retinal degeneration: no additive benefit.

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    Fabiana Di Marco

    Full Text Available The central nervous system undergoing degeneration can be stabilized, and in some models can be restored to function, by neuroprotective treatments. Photobiomodulation (PBM and dietary saffron are distinctive as neuroprotectants in that they upregulate protective mechanisms, without causing measurable tissue damage. This study reports a first attempt to combine the actions of PBM and saffron. Our working hypothesis was that the actions of PBM and saffron in protecting retinal photoreceptors, in a rat light damage model, would be additive. Results confirmed the neuroprotective potential of each used separately, but gave no evidence that their effects are additive. Detailed analysis suggests that there is actually a negative interaction between PBM and saffron when given simultaneously, with a consequent reduction of the neuroprotection. Specific testing will be required to understand the mechanisms involved and to establish whether there is clinical potential in combining neuroprotectants, to improve the quality of life of people affected by retinal pathology, such as age-related macular degeneration, the major cause of blindness and visual impairment in older adults.

  8. Investigation of the neuroprotective action of saffron (Crocus sativus L.) in aluminum-exposed adult mice through behavioral and neurobiochemical assessment.

    Science.gov (United States)

    Linardaki, Zacharoula I; Orkoula, Malvina G; Kokkosis, Alexandros G; Lamari, Fotini N; Margarity, Marigoula

    2013-02-01

    In the present study, the possible reversal effects of saffron against established aluminum (Al)-toxicity in adult mice, were investigated. Control, Al-treated (50 mg AlCl(3)/kg/day diluted in the drinking water for 5 weeks) and Al+saffron (Al-treatment as previously plus 60 mg saffron extract/kg/day intraperitoneally for the last 6 days), groups of male Balb-c mice were used. We assessed learning/memory, the activity of acetylcholinesterase [AChE, salt-(SS)/detergent-soluble(DS) isoforms], butyrylcholinesterase (BuChE, SS/DS isoforms), monoamine oxidase (MAO-A, MAO-B), the levels of lipid peroxidation (MDA) and reduced glutathione (GSH), in whole brain and cerebellum. Brain Al was determined by atomic absorption spectrometry, while, for the first time, crocetin, the main active metabolite of saffron, was determined in brain after intraperitoneal saffron administration by HPLC. Al intake caused memory impairment, significant decrease of AChE and BuChE activity, activation of brain MAO isoforms but inhibition of cerebellar MAO-B, significant elevation of brain MDA and significant reduction of GSH content. Although saffron extract co-administration had no effect on cognitive performance of mice, it reversed significantly the Al-induced changes in MAO activity and the levels of MDA and GSH. AChE activity was further significantly decreased in cerebral tissues of Al+saffron group. The biochemical changes support the neuroprotective potential of saffron under toxicity.

  9. (-)-Epigallocatechin-3-gallate (EGCG) modulates neurological function when intravenously infused in acute and, chronically injured spinal cord of adult rats.

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    Renno, Waleed M; Al-Khaledi, Ghanim; Mousa, Alyaa; Karam, Shaima M; Abul, Habib; Asfar, Sami

    2014-02-01

    Spinal cord injury (SCI) causes severe and long lasting motor and sensory deficits, chronic pain, and autonomic dysreflexia. (-)-epigallocatechin-3-gallate (EGCG) has shown to produce neuroprotective effect in a broad range of neurodegenerative disease animal models. This study designed to test the efficacy of intravenous infusion of EGCG for 36 h, in acutely injured rats' spinal cord: within first 4 h post-injury and, in chronically SC injured rats: after one year of injury. Functional outcomes measured using standard BBB scale, The Louisville Swim Scale (LSS) and, pain behavior assessment tests. 72 Female adult rats subjected to moderate thoracic SCI using MASCIS Impactor, blindly randomized as the following: (I) Acute SCI + EGCG (II) Acute SCI + saline. (III) Chronic SCI + EGCG. (IV) Chronic SCI + saline and, sham SCI animals. EGCG i.v. treatment of acute and, chronic SCI animals resulted in significantly better recovery of motor and sensory functions, BBB and LSS (P spinal cord increased (P < 0.001). Percent areas of GAP-43 and GFAP immunohistochemistry showed significant (P < 0.05) increase. We conclude that the therapeutic window of opportunity for EGCG to depict neurological recovery in SCI animals, is viable up to one year post SCI when intravenously infused for 36 h.

  10. Melatonin pretreatment protects against focal cerebral ischemia in the rat

    OpenAIRE

    Ho, HTS; Pei, Z; Pang, SF; Cheung, RTF

    2000-01-01

    Melatonin (MT) possesses many properties of an ideal neuroprotectant. In this study, the neuroprotective effects of exogenous MT were tested in a middle cerebral artery occlusion (MCAO) stroke model. Adult male Sprague-Dawley rats (280 to 360 g) were anesthetized with sodium pentobarbital (60 mg/kg, I.P.) to undergo reversible right-sided endovascular MCAO for 3 hours. Arterial blood pressure, heart rate and cerebral blood flow (CBF) were monitored, and rectal temperature was kept between 36....

  11. Effects of Fluoxetine and Visual Experience on Glutamatergic and GABAergic Synaptic Proteins in Adult Rat Visual Cortex.

    Science.gov (United States)

    Beshara, Simon; Beston, Brett R; Pinto, Joshua G A; Murphy, Kathryn M

    2015-01-01

    Fluoxetine has emerged as a novel treatment for persistent amblyopia because in adult animals it reinstates critical period-like ocular dominance plasticity and promotes recovery of visual acuity. Translation of these results from animal models to the clinic, however, has been challenging because of the lack of understanding of how this selective serotonin reuptake inhibitor affects glutamatergic and GABAergic synaptic mechanisms that are essential for experience-dependent plasticity. An appealing hypothesis is that fluoxetine recreates a critical period (CP)-like state by shifting synaptic mechanisms to be more juvenile. To test this we studied the effect of fluoxetine treatment in adult rats, alone or in combination with visual deprivation [monocular deprivation (MD)], on a set of highly conserved presynaptic and postsynaptic proteins (synapsin, synaptophysin, VGLUT1, VGAT, PSD-95, gephyrin, GluN1, GluA2, GluN2B, GluN2A, GABAAα1, GABAAα3). We did not find evidence that fluoxetine shifted the protein amounts or balances to a CP-like state. Instead, it drove the balances in favor of the more mature subunits (GluN2A, GABAAα1). In addition, when fluoxetine was paired with MD it created a neuroprotective-like environment by normalizing the glutamatergic gain found in adult MDs. Together, our results suggest that fluoxetine treatment creates a novel synaptic environment dominated by GluN2A- and GABAAα1-dependent plasticity.

  12. Contextual fear conditioning differs for infant, adolescent, and adult rats.

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    Esmorís-Arranz, Francisco J; Méndez, Cástor; Spear, Norman E

    2008-07-01

    Contextual fear conditioning was tested in infant, adolescent, and adult rats in terms of Pavlovian-conditioned suppression. When a discrete auditory-conditioned stimulus (CS) was paired with footshock (unconditioned stimulus, US) within the largely olfactory context, infants and adolescents conditioned to the context with substantial effectiveness, but adult rats did not. When unpaired presentations of the CS and US occurred within the context, contextual fear conditioning was strong for adults, weak for infants, but about as strong for adolescents as when pairings of CS and US occurred in the context. Nonreinforced presentations of either the CS or context markedly reduced contextual fear conditioning in infants, but, in adolescents, CS extinction had no effect on contextual fear conditioning, although context extinction significantly reduced it. Neither CS extinction nor context extinction affected responding to the CS-context compound in infants, suggesting striking discrimination between the compound and its components. Female adolescents showed the same lack of effect of component extinction on response to the compound as infants, but CS extinction reduced responding to the compound in adolescent males, a sex difference seen also in adults. Theoretical implications are discussed for the development of perceptual-cognitive processing and hippocampus role.

  13. Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

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    Sanchez-Criado Jose E

    2004-09-01

    Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

  14. Aspects of Growth Hormone and Insulin-Like Growth Factor-I Related to Neuroprotection, Regeneration, and Functional Plasticity in the Adult Brain

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    N. David Åberg

    2006-01-01

    Full Text Available Apart from regulating somatic growth and metabolic processes, accumulating evidence suggests that the growth hormone (GH/insulin-like growth factor-I (IGF-I axis is involved in the regulation of brain growth, development, and myelination. In addition, both GH and IGF-I affect cognition and biochemistry in the adult brain. Some of the effects of GH are attributable to circulating IGF-I, while others may be due to IGF-I produced locally within the brain. Some of the shared effects in common to GH and IGF-I may also be explained by cross-talk between the GH and IGF-I transduction pathways, as indicated by recent data from other cell systems. Otherwise, it also seems that GH may act directly without involving IGF-I (either circulating or locally. Plasticity in the central nervous system (CNS may be viewed as changes in the functional interplay between the major cell types, neurons, astrocytes, and oligodendrocytes. GH and IGF-I affect all three of these cell types in several ways. Apart from the neuroprotective effects of GH and IGF-I posited in different experimental models of CNS injury, IGF-I has been found to increase progenitor cell proliferation and new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. It appears that the MAPK signaling pathway is required for IGF-I–stimulated proliferation in vitro, whereas the PI3K/Akt or MAPK/Erk signaling pathway appears to mediate antiapoptotic effects. The increase of IGF-I on endothelial cell phenotype may explain the increase in cerebral arteriole density observed after GH treatment. The functional role of GH and IGF-I in the adult brain will be reviewed with reference to neurotransmitters, glucose metabolism, cerebral blood flow, gap junctional communication, dendritic arborization, exercise, enriched environment, depression, learning, memory, and aging.Briefly, these findings suggest that IGF-I functions as a putative regenerative agent in the adult CNS. Hitherto

  15. Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition

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    D.Y. Xia

    2013-08-01

    Full Text Available Sublethal ischemic preconditioning (IPC is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration, 5×5 min (5 min duration, 2 episodes, 15-min interval, 5×5×5 min (5 min duration, 3 episodes, 15-min intervals, and 15 min (15 min duration, and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis.

  16. Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Xia, D.Y. [Department of Neurology, Navy General Hospital of PLA, Beijing (China); Li, W. [General Hospital of Shenyang Military Command, Department of Neurology, Shenyang, China, Department of Neurology, General Hospital of Shenyang Military Command, Shenyang (China); Qian, H.R.; Yao, S.; Liu, J.G.; Qi, X.K. [Department of Neurology, Navy General Hospital of PLA, Beijing (China)

    2013-08-10

    Sublethal ischemic preconditioning (IPC) is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration), 5×5 min (5 min duration, 2 episodes, 15-min interval), 5×5×5 min (5 min duration, 3 episodes, 15-min intervals), and 15 min (15 min duration), and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1)-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R) injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis.

  17. Transplanted Neural Stem Cells: Playing a Neuroprotective Role by Ceruloplasmin in the Substantia Nigra of PD Model Rats?

    Science.gov (United States)

    Xiao, Jia-Jia; Yin, Ming; Wang, Ze-Jian; Wang, Xiao-Ping

    2015-01-01

    Although mounting evidence suggests that ceruloplasmin (CP) deficiency and iron deposition are pivotal factors responsible for exacerbating demise of dopaminergic neurons in the substantia nigra (SN) of the Parkinsonism and neural stem cells (NSCs) are believed to be excellent candidates for compensating the lost dopaminergic neurons, there are few researches to explore the change of CP expression and of iron deposition in the pathological microenvironment of SN after NSCs transplantation and the ability of grafted NSCs to differentiate directionally into dopaminergic neurons under the changed homeostasis. With substantia nigral stereotaxic technique and NSCs transplantation, we found that tyrosine hydroxylase and CP expression decreased and iron deposition increased in the lesioned SN after 6-OHDA administration compared with control, while tyrosine hydroxylase and CP expression increased and iron deposition decreased after NSCs transplantation compared to 6-OHDA administration alone. Only a small number of embedding NSCs are able to differentiate into dopaminergic neurons. These results suggest that grafted NSCs have an influence on improving the content of CP expression, which may play a neuroprotective role by decreasing iron deposition and ameliorating damage of dopaminergic neurons and possibly underline the iron-related common mechanism of Parkinson's disease and Wilson's disease.

  18. Transplantation of Neural Stem Cells Cotreated with Thyroid Hormone and GDNF Gene Induces Neuroprotection in Rats of Chronic Experimental Allergic Encephalomyelitis

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    Xiaoqing Gao

    2016-01-01

    Full Text Available The present study investigates whether transplantation of NSCs treated with T3 alone (T3/NSCs, or in conjunction with GDNF gene (GDNF-T3/NSCs, provides a better therapeutic effect than NSCs for chronic EAE. EAE rats were, respectively, injected with NSCs, T3/NSCs, GDNF-T3/NSCs, and saline at 10 days and sacrificed at 60 days after EAE immunization. The three cell grafted groups showed a significant reduction in clinical scores, inflammatory infiltration, and demyelination compared with the saline-injected group, and among the cell grafted groups, the reduction in GDNF-T3/NSCs group was the most notable, followed by T3/NSCs group. Grafted T3/NSCs and GDNF-T3/NSCs acquired more MAP2, GalC, and less GFAP in brain compared with grafted NSCs, and grafted GDNF-T3/NSCs acquired most MAP2 and least GalC among the cell grafted groups. Furthermore, T3/NSCs and GDNF-T3/NSCs grafting increased the expression of mRNA for PDGFαR, GalC, and MBP in lesion areas of brain compared with NSCs grafting, and the expression of mRNA for GalC and MBP in GDNF-T3/NSCs group was higher than that in T3/NSCs group. In conclusion, T3/NSCs grafting, especially GDNF-T3/NSCs grafting, provides a better neuroprotective effect for EAE than NSCs transplantation.

  19. [Effect of the novel nootropic and neuroprotective dipeptide noopept on the streptozotocin-induced model of sporadic Alzheimer disease in rats].

    Science.gov (United States)

    Ostrovskaia, R U; Tsaplina, A P; Vakhitova, Iu V; Salimgareeva, M Kh; Iamidanov, R S

    2010-01-01

    Streptozotocin-intracerebroventricularly treated rats are proposed as an experimental model of sporadic Alzheimer disease (AD). Diabetogenic toxin streptozotocin (STZ) administered in both cerebral ventricles in a dose of 3 mg/kg decreases the expression of NGF and BDNF mainly in the hippocampus and increases the content of malonic dialdehyde (MDA)--a product of lipid peroxidation--in the brain tissues. These metabolic changes are accompanied by a pronounced cognitive deficiency, which is manifested by long-term memory deterioration in the passive avoidance test. These manifestations of pathology are not accompanied by hyperglycemia in the case of intraventricular STZ administration, in contrast to the systemic (in particular, intraperitoneal) route of introduction that causes a pronounced increase in the blood glucose level. These results are consistent with the existing notions that (i) STZ administered intraventricularly provokes a complex of changes imitating the sporadic AD and (ii) this disease can be considered as a manifestation of type-III diabetes. The new original cognition enhancing and neuroprotective dipeptide noopept decreases the aforementioned metabolic changes and the accompanying long-term deterioration of the memory. Previously, this systemically active dipeptide was shown to be capable of increasing expression of NGF and BDNF in the hippocampus, stimulating the antibody production to beta-amyloid, inhibiting the lipid peroxidation, activating the endogenous antioxidant systems, and decreasing the rate of glutamate release (cholinopositive effect). Taken together, these data indicate that noopept can be considered as a multipotent substance acting upon several important pathogenic chainsof the sporadic AD.

  20. Bcl-2, Bcl-xL, and p-AKT are involved in neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma

    Science.gov (United States)

    Phatak, Nitasha R.; Stankowska, Dorota L.

    2016-01-01

    Purpose Brn3b is a class IV POU domain transcription factor that plays an important role in the development of retinal ganglion cells (RGCs), RGC survival, and particularly axon growth and pathfinding. Our previous study demonstrated that recombinant adenoassociated virus serotype 2 (rAAV-2)–mediated overexpression of Brn3b in RGCs promoted neuroprotection in a rodent model of glaucoma. However, the mechanisms underlying neuroprotection of RGCs in rats overexpressing Brn3b in animal models of glaucoma remain largely unknown. The goal of this study was to understand some of the mechanisms underlying the neuroprotection of RGCs overexpressing Brn3b during intraocular pressure (IOP) elevation in Brown Norway rats. Methods One eye of Brown Norway rats (Rattus norvegicus) was injected with an AAV construct encoding either green fluorescent protein (GFP; recombinant adenoassociated virus–green fluorescent protein, rAAV-hSyn-GFP) or Brn3b (rAAV-hSyn-Brn3b). Expression of antiapoptotic proteins, including B cell lymphoma/leukemia-2 (Bcl-2) family proteins (Bcl-2 and Bcl-xL), and p-AKT, was observed following immunostaining of rat retinas that overexpress Brn3b. In a different set of experiments, intraocular pressure was elevated in one eye of Brown Norway rats, which was followed by intravitreal injection with AAV constructs encoding either GFP (rAAV-CMV-GFP) or Brn3b (rAAV-CMV-Brn3b). Retinal sections were stained for prosurvival factors, including Bcl-2, Bcl-XL, and p-AKT. Results AAV-mediated expression of transcription factor Brn3b promoted statistically significant upregulation of the Bcl-2 protein and increased expression of p-AKT in RGCs of Brown Norway rats. In addition, following IOP elevation, AAV-mediated Brn3b expression also statistically significantly increased levels of Bcl-2 in the RGC layer in Brown Norway rats. Conclusions Adenoassociated virus–mediated Brn3b protein overexpression may promote neuroprotection by upregulating key antiapoptotic

  1. Comparative study on influence of fetal bovine serum and serum of adult rat on cultivation of newborn rat neural cells

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    Sukach A. N.

    2014-09-01

    Full Text Available Aim. To study the influence of fetal bovine serum and serum of adult rats on behavior of newborn rat isolated neural cells during their cultivation in vitro. Methods. The isolation of neural cells from neonatal rat brain. The determination of the dynamics of cellular monolayer formation. Immunocytochemical staining of cells for β-tubulin III, nestin and vimentin. Results. It has been determined that the addition of serum of adult rats to the cultivation medium creates more favorable conditions for survival, attachment and spread of differentiated, and proliferation of the stem/progenitor neural cells of newborn rats during cultivation in vitro compared with the fetal bovine serum. Conclusions. Using the serum of adult rats is preferable for the cultivation of isolated neural cells of newborn rats compared with the fetal bovine serum.

  2. Opposing needling promotes behavior recovery and exerts neuroprotection via the cAMP/PKA/CREB signal transduction pathway in transient MCAO rats

    Science.gov (United States)

    JIANG, YIJING; YANG, SHANLI; TAO, JING; LIN, ZHICHENG; YE, XIAOQIAN; YOU, YONGMEI; PENG, JUN; HONG, ZHENFENG; CHEN, LIDIAN

    2016-01-01

    The aim of the present study was to investigate whether the cyclic adenosine 3′,5′-monophosphate (cAMP)/protein kinase A(PKA)/cAMP-responsive element binding protein (CREB) signal transduction pathway triggered by γ-aminobutyric acid class B (GABAB) receptor activation is involved in neuroprotection against ischemia and behavioral recovery induced by opposing needling (ON). A total of 80 rats were randomly divided into four groups: A sham operation group, an ischemia group, an ON group and an ON group effectively inhibited by the GABAB receptor antagonist, CGP35384 (n=20/group). The behavior of the rats was assessed by their neurological deficit score, whereas the impairment of gait was examined using the CatWalk system. The volume of cerebral infarction was examined upon treatment with 2,3,5-triphenyltetrazolium chloride. The expression levels of CREB, GABAB1 and GABAB2 were examined by western blotting and reverse transcription-quantitative polymerase chain reaction, and the activity of adenylyl cyclase (AC), cAMP and PKA in the serum was detected using an enzyme-linked immunosorbent assay. In the present study, in comparison with other groups, the ON group exhibited a reduced score for the neurological deficit, the stride length and swing speed were improved, and the volume of infarction was reduced. However, these effects were reversed upon administration of CGP35384. Additionally, the expression levels of CREB, GABAB1 and GABAB2 were increased in the ON group. The levels of AC, cAMP and PKA in the serum were also increased in the ON group, whereas the addition of CGP35384 reversed these effects. The results of the present study demonstrated that ON markedly protected the brain against transient cerebral ischemic injury, and this effect was possibly mediated by the activation of the GABAB/cAMP/PKA/CREB signal transduction pathway. These findings implied that ON may be a potential therapeutic method for treating stroke. PMID:26780954

  3. Involvement of brain-derived neurotrophic factor and neurogenesis in oestradiol neuroprotection of the hippocampus of hypertensive rats.

    Science.gov (United States)

    Pietranera, L; Lima, A; Roig, P; De Nicola, A F

    2010-10-01

    The hippocampus of spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)-salt hypertensive rats shows decreased cell proliferation and astrogliosis as well as a reduced number of hilar cells. These defects are corrected after administration of 17β-oestradiol (E(2) ) for 2 weeks. The present work investigated whether E(2) treatment of SHR and of hypertensive DOCA-salt male rats modulated the expression of brain-derived neurotrophic factor (BDNF), a neurotrophin involved in hippocampal neurogenesis. The neurogenic response to E(2) was simultaneously determined by counting the number of doublecortin-immunopositive immature neurones in the subgranular zone of the dentate gyrus. Both hypertensive models showed decreased expression of BDNF mRNA in the granular zone of the dentate gyrus, without changes in CA1 or CA3 pyramidal cell layers, decreased BDNF protein levels in whole hippocampal tissue, low density of doublecortin (DCX)-positive immature neurones in the subgranule zone and decreased length of DCX+ neurites in the dentate gyrus. After s.c. implantation of a single E(2) pellet for 2 weeks, BDNF mRNA in the dentate gyrus, BDNF protein in whole hippocampus, DCX immunopositive cells and the length of DCX+ neurites were significantly raised in both SHR and DOCA-salt-treated rats. These results indicate that: (i) low BDNF expression and deficient neurogenesis distinguished the hippocampus of SHR and DOCA-salt hypertensive rats and (ii) E(2) was able to normalise these biologically important functions in the hippocampus of hypertensive animals.

  4. Effect of piperine on the epididymis of adult male rats

    Institute of Scientific and Technical Information of China (English)

    S. C. D'cruz; P. P. Mathur

    2005-01-01

    Aim: To study the effect of piperine on the epididymal antioxidant system of adult male rats. Methods: Adult male rats were orally administered piperine at doses of 1 mg/kg, 10 mg/kg and 100 mg/kg body weight each day for 30consecutive days. Twenty-four hours after the last treatment, the rats were weighed and killed with ether and the epididymis was dissected from the bodies. Sperm collected from the cauda region of the epididymis was used for the assessment of its count, motility and viability. Caput, corpus and cauda regions of the epididymis were separated and homogenized separately to obtain 10 % homogenates. The supernatants were used for the assays of sialic acid,superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, lipid peroxidation and hydrogen peroxide generation. Results: Body weight of the piperine-treated rats remained unchanged. The weights of the caput,corpus and cauda regions of the epididymis significantly decreased at dose of 100 mg/kg. Epididymal sperm count and motility decreased at 10 mg/kg and 100 mg/kg, and sperm viability decreased significantly at 100 mg/kg. Sialic acid levels in the epididymis decreased significantly at 100 mg/kg while significant decrease in the cauda region alone was observed at 10 mg/kg. A significant decline in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, along with an increase in hydrogen peroxide generation and lipid peroxidation were observed at 10 mg/kg and 100 mg/kg. Conclusion: Piperine caused a decrease in the activity of antioxidant enzymes and sialic acid levels in the epididymis and thereby increased reactive oxygen species levels that could damage the epididymal environment and sperm function.

  5. Basement membrane chondroitin sulfate proteoglycans: localization in adult rat tissues

    DEFF Research Database (Denmark)

    McCarthy, K J; Couchman, J R

    1990-01-01

    Heparan sulfate proteoglycans have been described as the major proteoglycan component of basement membranes. However, previous investigators have also provided evidence for the presence of chondroitin sulfate glycosaminoglycan in these structures. Recently we described the production...... and characterization of core protein-specific monoclonal antibodies (MAb) against a chondroitin sulfate proteoglycan (CSPG) present in Reichert's membrane, a transient extra-embryonic structure of rodents. This CSPG was also demonstrated to be present in adult rat kidney. We report here the tissue distribution...... sulfate proteoglycans previously described....

  6. Neuroprotective Effect of Isoflurane in Rats with Traumatic Brain Injury and Its Mechanism%异氟烷对创伤性脑损伤大鼠的神经保护作用及作用机制研究

    Institute of Scientific and Technical Information of China (English)

    张睿; 杨祖悌; 张同寅; 宋海军; 王斌

    2015-01-01

    Objective To investigate the neuroprotective effect of isoflurane in rats with traumatic brain injury and its mechanism. Methods A total of 80 healthy male adult S-D rats were selected and divided into groups A,B,C,D,each of 20 rats. Modified Feeney freely falling body method was used to prepare rat model of traumatic brain injury,rats of A group were given open-window operation,rats of B group were given continue anesthesia of isoflurane before prepartion,rats of C group and D group were given CPR after preparation,and rats of D group were given extra continue anesthesia of isoflurane after CPR. NSS was used to evaluate the neurologic deficits after 12 hours and 24 hours of traumatic brain injury,immunoblotting was used to detect the protein expression of P-Akt,P-GSK3β,Bcl-2 and cleaved-caspase-3 in brain tissues around nidus after 24 hours of traumatic brain injury,and TUNEL was used to detect the apoptotic nerve cell amount in brain tissues around nidus after 24 hours of traumatic brain injury. Results NSS score after 12 hours and 24 hours of traumatic brain injury of C group was statistically significantly higher than that of A group,B group and D group,respectively,and that of B group and D group was statistically significantly higher than that of A group ( P<0. 05 ). Protein expression of P-Akt and P-GSK3β in brain tissues around nidus after 24 hours of traumatic brain injury of B group,C group and D group were statistically significantly higher than those of A group,those of B group and D group were statistically significantly higher than those of C group( P<0. 05). Protein expression of Bcl -2 in brain tissues around nidus after 24 hours of traumatic brain injury of C group was statistically significantly lower than that of A group,B group and D group,respectively,while protein expression of cleaved-caspase-3 and apoptotic nerve cell amount of C group were statistically significantly higher than those of A group,B group and D group,protein expression of

  7. Neuroprotective role of antioxidant and pyranocarboxylic acid derivative against AlCl3 induced Alzheimer’s disease in rats

    Institute of Scientific and Technical Information of China (English)

    Sarabjeet Singh; Ramandeep Singh; Ajay S Kushwah; Gaurav Gupta

    2014-01-01

    Objective: To assess potential of quercetin and etodolac to treat oxidative stress in neuronal death and inflammation in Alzheimer’s disease of AlCl3 induced rat models. All results of this AlCl3 model are compared with those obtained in controls.Methods:Wistar rats, housed in a controlled environment were treated with aluminum chloride (4.2 mg/kg of body weight, i.p.) for 28 d rather than oral to ensure neurotoxic concentration in hippocampus and hypothalamic region, part highly active in memory control and cognition, while control group was injected with saline. Estimation of thiobarbituric acid reactive substance, superoxide dismutase, reduced glutathione and acetylcholine levels gave estimation of neuronal damage. Low (20 mg/kg and 25 mg/kg) and high (40 mg/kg and 50 mg/kg) doses of quercetin and etodolac were administered to the test groups respectively. Histopathology study was conducted to perform relative study.Results:Co-administration of quercetin and etodolac either alone or in combination prevented the changes in biochemical markers of Alzheimer’s disease, but significant results (P<0.05) were seen when a combination of two was administered at low dose levels. Good correlation was developed between chemical estimations and histopathology study.Conclusions:Our findings suggest a combined role of anti-oxidant and cyclooxygenase inhibitor in protection of neural degeneration and inflammation due to oxidative stress.

  8. Synergistical neuroprotection of rofecoxib and statins against malonic acid induced Huntington's disease like symptoms and related cognitive dysfunction in rats.

    Science.gov (United States)

    Kumar, Anil; Sharma, Neha; Mishra, Jitendriya; Kalonia, Harikesh

    2013-06-05

    Malonic acid (MA) is a reversible inhibitor of succinate dehydrogenase (SDH) which induces mitochondrial dysfunction followed by secondary excitotoxicity and apoptosis due to generation of reactive oxygen species. Therapeutic potential of rofecoxib and statins have been well documented in several experimental models of neurodegenerative disorders, however, its exact mechanism of action is not known properly. Therefore, the present study is an attempt to investigate the effect of rofecoxib along with the statins against MA induced behavioural and biochemical alterations in rats. Single intrastriatal MA (6 µmol) significantly caused motor incordination, memory dysfunction and alteration in the antioxidant enzyme levels, mitochondrial enzyme complex (I, II, IV) activities, mitochondrial redox ratio and pro-inflammatory cytokine [tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] levels in the striatum as compared to the naive group. Fourteen days treatment with rofecoxib, atorvastatin, simvastatin significantly attenuated these behavioural, biochemical, and cellular alterations as compared to control (MA treated group). However, the treatment of rofecoxib along with atorvastatin or simvastatin significantly attenuated these behavioural, biochemical, and cellular alterations as compared to their individual effects. The results of the present study demonstrated that rofecoxib modulates the protective effects of statins against MA-induced neurobehavioral and related biochemical and cellular alterations in rats. This further provides evidence toward the involvement of neuroinflammatory cascade in the pathogenesis of Huntington's disease.

  9. Neuroprotective potential of Bacopa monnieri and Bacoside A against dopamine receptor dysfunction in the cerebral cortex of neonatal hypoglycaemic rats.

    Science.gov (United States)

    Thomas, Roshni Baby; Joy, Shilpa; Ajayan, M S; Paulose, C S

    2013-11-01

    Neonatal hypoglycaemia initiates a series of events leading to neuronal death, even if glucose and glycogen stores return to normal. Disturbances in the cortical dopaminergic function affect memory and cognition. We recommend Bacopa monnieri extract or Bacoside A to treat neonatal hypoglycaemia. We investigated the alterations in dopaminergic functions by studying the Dopamine D1 and D2 receptor subtypes. Receptor-binding studies revealed a significant decrease (p Bacoside A ameliorated the dopaminergic and cAMP imbalance as effectively as the glucose therapy. The upregulated Bax expression in the present study indicates the high cell death in hypoglycaemic neonatal rats. Enzyme assay of SOD confirmed cortical cell death due to free radical accumulation. The gene expression of SOD in the cortex was significantly downregulated (p < 0.001). Bacopa treatment showed a significant reversal in the altered gene expression parameters (p < 0.001) of Bax and SOD. Our results suggest that in the rat experimental model of neonatal hypoglycaemia, Bacopa extract improved alterations in D1, D2 receptor expression, cAMP signalling and cell death resulting from oxidative stress. This is an important area of study given the significant motor and cognitive impairment that may arise from neonatal hypoglycaemia if proper treatment is not implemented.

  10. Kongsheng Zhenzhong pill's effect on the learning and memory ability and its neuroprotective effects in vascular dementia rats

    Institute of Scientific and Technical Information of China (English)

    Xuming Ji; Huayun Yu; Bin Ouyang; Guowei Liu; Zhichun Wu; Heng Liu; Fang Du

    2011-01-01

    Clinical reports have demonstrated that the Kongsheng Zhenzhong pill (KSZZP), a classical prescriptionderiving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However, the mechanisms that mediate its effects remain unclear. In this study,the expression of N-methyl-D-aspartate receptor 1 mRNA, the content of nitric oxide, and the concentrationof calcium in neurons was determined with in situ hybridization, spectrophotometry and flow cytometry, respectively. In addition, the expressions of N-methyl-D-aspartate receptor 1, nervegrowth factor protein, and glial cell line-derived neurotrophic factor protein w ere detected with immunohis tochemistry.We found that KSZZP could significantly decrease the expression of N-methyl-D-aspartate receptor 1 mRNA and protein, the content of nitric oxide, and the concentration of calcium in neurons. KSZZP also increased the expression of nerve growth factor and glialcell line-derived neurotrophic factor protein in the hippocampus CA1 region and in the cerebralcortex. Morris water maze and passive avoidance tests verified that KSZZP ameliorated the cognitiveimpairments of vascular dementia rats. Moreover, the KSZZP-induced improvements in thecognitive functions of vascular dementia rats were correlated with both inhibition of N-methyl-D-aspartate-induced excitable neurotoxicity and elevation of neurotrophic factor expression.

  11. 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

  12. Dobutamine stress echocardiography in healthy adult male rats

    Directory of Open Access Journals (Sweden)

    Couet Jacques

    2005-10-01

    Full Text Available Abstract Background Dobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response. Methods 15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intravenously under continuous imaging of the heart by a 12 MHz ultrasound probe. Results Dobutamine stress echocardiography reduced gradually LV diastolic and systolic dimensions. Ejection fraction increased by a mean of +24% vs. baseline. Heart rate increased progressively without reaching a plateau. Changes in LV dimensions and ejection fraction reached a plateau after a mean of 4 minutes at a constant infusion rate. Conclusion DSE can be easily performed in rats. The normal response is an increase in heart rate and ejection fraction and a decrease in LV dimensions. A plateau in echocardiographic measurements is obtained after 4 minutes of a constant infusion rate in most animals.

  13. Lipoic acid attenuates Aroclor 1260-induced hepatotoxicity in adult rats.

    Science.gov (United States)

    Aly, Hamdy A A; Mansour, Ahmed M; Hassan, Memy H; Abd-Ellah, Mohamed F

    2016-08-01

    The present study was aimed to investigate the mechanistic aspect of Aroclor 1260-induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high-density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase-3 & -9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260-induced liver injury. Lipoic acid could protect rats against Aroclor 1260-induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913-922, 2016.

  14. Acute behavioral toxicity of carbaryl and propoxur in adult rats.

    Science.gov (United States)

    Ruppert, P H; Cook, L L; Dean, K F; Reiter, L W

    1983-04-01

    Motor activity and neuromotor function were examined in adult CD rats exposed to either carbaryl or propoxur, and behavioral effects were compared with the time course of cholinesterase inhibition. Rats received an IP injection of either 0, 2, 4, 6 or 8 mg/kg propoxur or 0, 4, 8, 16 or 28 mg/kg carbaryl in corn oil 20 min before testing. All doses of propoxur reduced 2 hr activity in a figure-eight maze, and crossovers and rears in an open field. For carbaryl, dosages of 8, 16 and 28 mg/kg decreased maze activity whereas 16 and 28 mg/kg reduced open field activity. In order to determine the time course of effects, rats received a single IP injection of either corn oil, 2 mg/kg propoxur or 16 mg/kg carbaryl, and were tested for 5 min in a figure-eight maze either 15, 30, 60, 120 or 240 min post-injection. Immediately after testing, animals were sacrificed and total cholinesterase was measured. Maximum effects of propoxur and carbaryl on blood and brain cholinesterase and motor activity were seen within 15 min. Maze activity had returned to control levels within 30 and 60 min whereas cholinesterase levels remained depressed for 120 and 240 min for propoxur and carbaryl, respectively. These results indicate that both carbamates decrease motor activity, but behavioral recovery occurs prior to that of cholinesterase following acute exposure.

  15. Fast, potent pharmacological expansion of endogenous hes3+/sox2+ cells in the adult mouse and rat hippocampus.

    Directory of Open Access Journals (Sweden)

    Simone Pacioni

    Full Text Available The adult hippocampus is involved in learning and memory. As a consequence, it is a brain region of remarkable plasticity. This plasticity exhibits itself both as cellular changes and neurogenesis. For neurogenesis to occur, a population of local stem cells and progenitor cells is maintained in the adult brain and these are able to proliferate and differentiate into neurons which contribute to the hippocampal circuitry. There is much interest in understanding the role of immature cells in the hippocampus, in relation to learning and memory. Methods and mechanisms that increase the numbers of these cells will be valuable in this research field. We show here that single injections of soluble factors into the lateral ventricle of adult rats and mice induces the rapid (within one week increase in the number of putative stem cells/progenitor cells in the hippocampus. The established progenitor marker Sox2 together with the more recently established marker Hes3, were used to quantify the manipulation of the Sox2/Hes3 double-positive cell population. We report that in both adult rodent species, Sox2+/Hes3+ cell numbers can be increased within one week. The most prominent increase was observed in the hilus of the dentate gyrus. This study presents a fast, pharmacological method to manipulate the numbers of endogenous putative stem cells/progenitor cells. This method may be easily modified to alter the degree of activation (e.g. by the use of osmotic pumps for delivery, or by repeat injections through implanted cannulas, in order to be best adapted to different paradigms of research (neurodegenerative disease, neuroprotection, learning, memory, plasticity, etc.

  16. A comparison of neuroprotective efficacy of two novel reactivators of acetylcholinesterase called K920 and K923 with the oxime K203 and trimedoxime in tabun-poisoned rats.

    Science.gov (United States)

    Kassa, Jiri; Misik, Jan; Hatlapatkova, Jana; Zdarova Karasova, Jana

    2017-01-22

    The ability of two newly developed bispyridinium oximes (K920, K923) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with the oxime K203 and trimedoxime using a functional observational battery (FOB). The neuroprotective effects of the oximes studied combined with atropine on rats poisoned with tabun at a sublethal dose (130 μg/kg i.m.; 80% of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by FOB at 2 h after tabun administration. The results indicate that all tested oximes combined with atropine enable tabun-poisoned rats to survive till the end of experiment while one non-treated tabun-poisoned rat died within 2 h. Both newly developed oximes (K920, K923) combined with atropine were able to markedly decrease tabun-induced neurotoxicity in the case of sublethal poisoning although they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. Their ability to decrease tabun-induced acute neurotoxicity did not prevail the neuroprotective efficacy of trimedoxime and the oxime K203. Therefore, the newly developed oximes are not suitable for the replacement of currently available oximes (especially trimedoxime) in the treatment of acute tabun poisonings.

  17. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injur y in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Wangxin Zhang; Qiuling Zhang; Wen Deng; Yalu Li; Guoqing Xing; Xianjun Shi; Yifeng Du

    2014-01-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both an-ti-oxidative and anti-inlfammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoder-ma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis fac-tor-αand interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. hTese results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and an-ti-inlfammatory actions.

  18. Neuroprotective effects of pretreatment with quercetin as assessed by acetylcholinesterase assay and behavioral testing in poloxamer-407 induced hyperlipidemic rats.

    Science.gov (United States)

    Braun, Josiane B S; Ruchel, Jader B; Adefegha, Stephen A; Coelho, Ana Paula V; Trelles, Kelly B; Signor, Cristiane; Rubin, Maribel A; Oliveira, Juliana S; Dornelles, Guilherme L; de Andrade, Cinthia M; Castilhos, Lívia G; Leal, Daniela B R

    2017-04-01

    Hyperlipidemia is a group of disorders characterized by excessive lipids in the bloodstream. It is associated with the incidence of cardiovascular diseases and recognized as the most important factor underlying the occurrence of atherosclerosis. This study was conducted to investigate whether pretreatment with quercetin can protect against possible memory impairment and deterioration of the cholinergic system in hyperlipidemic rats. Animals were divided into ten groups (n=7): saline/control, saline/quercetin 5mg/kg, saline/quercetin 25mg/kg, saline/quercetin 50mg/kg, saline/simvastatin (0.04mg/kg), hyperlipidemia, hyperlipidemia/quercetin 5mg/kg, hyperlipidemia/quercetin 25mg/kg, hyperlipidemia/quercetin 50mg/kg and hyperlipidemia/simvastatin. The animals were pretreated with quercetin by oral gavage for a period of 30days and hyperlipidemia was subsequently induced by intraperitoneal administration of a single dose of 500mg/kg of poloxamer-407. Simvastatin was administered after the induction of hyperlipidemia. The results demonstrated that hyperlipidemic rats had memory impairment compared with the saline control group (P<0.001). However, pretreatment with quercetin and simvastatin treatment attenuated the damage caused by hyperlipidemia compared with the hyperlipidemic group (P<0.05). Acetylcholinesterase (AChE) activity in the cerebral hippocampus was significantly (P<0.001) reduced in the hyperlipidemic group compared with the control saline group. Pretreatment with quercetin and simvastatin treatment in the hyperlipidemic groups significantly (P<0.05) increased AChE activity compared with the hyperlipidemic group. Our results thus suggest that quercetin may prevent memory impairment, alter lipid metabolism, and modulate AChE activity in an experimental model of hyperlipidemia.

  19. Effects of neonatal peripheral tissue injury on pain-related behaviors in adult rats

    Directory of Open Access Journals (Sweden)

    Meng-meng LI

    2013-09-01

    Full Text Available Objective To observe the effects of peripheraltissueinjury in the developmental stage of newborn rats on pain-related behaviors in adult rats. Methods SD rats 1,4,7,14,21 and 28days after birth were selected in thepresent study(4litters at each time point and 10 rats per litter.Each litter of rats was randomly divided intoinjury group(receiving subcutaneous injection of 20μl bee venomand control group(receiving subcutaneous injection of 20μl normal saline, with20 in each group, and then raised for 2 months to adulthood. The baseline pain threshold was observed by measuring spontaneous paw flinching reflex,paw withdrawal thermal latency(PWTLand paw withdrawal mechanical threshold(PWMT, then 50μl 0.4% bee venom was subcutaneously injected to each rat, and the changesinpa in reaction and pain threshold were determined. Results The baseline thermal pain threshold in adult rats receiving bee venom or normal saline at different time points after birth was similar,but baseline mechanical pain threshold in adult rats receiving bee venom at1,4,7and14 days after birth was decreased significantly compared with the adult rats receiving normal saline at corresponding time points(P0.05.Mechanical hyperalgesia was not induced in rats injected with bee venom but induced in adult ratsinjected with normal saline4-21days after birth.Injection of bee venom 21 and 28 days after birth could obviously enhance the bee venom-induced hyperalgesiain adult rats compared with control group(P<0.01. Conclusions Bee venom stimuli at different time points after birth could affect the baseline PWMT and mechanical pain hypersensitivityin adult rats but not the baseline PWTL and thermal pain hypersensitivity. The 21st day maybe a key time point of nervous system development in rats.

  20. Neonatal caffeine exposure and seizure susceptibility in adult rats.

    Science.gov (United States)

    Guillet, R; Dunham, L

    1995-08-01

    Early developmental exposure to caffeine in rats results in changes in brain excitability that persist to adulthood. The mechanism of these alterations is unknown. To identify potential neurotransmitter systems involved, we exposed neonatal rats to caffeine and determined seizure thresholds for chemoconvulsants active at different CNS receptors in the adult animal. Rats were unhandled (NH) or received by gavage (0.05 ml/10 g) either vehicle (water) or caffeine (15-20 mg/kg/day) for postnatal days 2-6. At age 70-90 days, each rat was infused intravenously (i.v.) with picrotoxin (PIC), bicuculline (BIC) [convulsants acting at the gamma-aminobutyric acid/benzodiazepine (GABA/BDZ) receptor], pentylenetetrazol [PTZ, possibly acting at both GABA/BDZ and N-methyl-D-aspartate (NMDA) receptors], caffeine (acting at adenosine receptors), strychnine (STR, acting at glycine receptors), or kainic acid (KA, acting at the NMDA receptor). Seizure thresholds were analyzed as a function of neonatal treatment and sex. Thresholds for caffeine, PTZ, PIC, and KA were increased as a function of neonatal caffeine exposure (p = 0.01, 0.02, 0.02, and 0.005, respectively). The thresholds for BIC and STR were not altered. There were also gender differences in seizure susceptibility. Thresholds for seizures produced by BIC, caffeine, PIC, and STR were higher in females (p = 0.005, 0.005, 0.001, and 0.0001, respectively), but were not different for seizures caused by PTZ. These results suggest that early developmental exposure to caffeine affects later seizure susceptibility. Moreover, some of these effects are gender specific.

  1. Contractile force measured in unskinned isolated adult rat heart fibres.

    Science.gov (United States)

    Brady, A J; Tan, S T; Ricchiuti, N V

    1979-12-13

    A number of investigators have succeeded in preparing isolated cardiac cells by enzymatic digestion which tolerate external [Ca2+] in the millimolar range. However, a persistent problem with these preparations is that, unlike in situ adult ventricular fibres, the isolated fibres usually beat spontaneously. This spontaneity suggests persistent ionic leakage not present in situ. A preferable preparation for mechanical and electrical studies would be one which is quiescent but excitable in response to electrical stimulation and which does not undergo contracture with repeated stimulation. We report here a modified method of cardiac fibre isolation and perfusion which leaves the fibre membrane electrically excitable and moderately resistant to mechanical stress so that the attachment of suction micropipettes to the fibre is possible for force measurement and length control. Force generation in single isolated adult rat heart fibres is consistent with in situ contractile force. The negative staircase effect (treppe) characteristic of adult not heart tissue is present with increased frequency of stimulation. Isometric developed tension increases with fibre length as in in situ ventricular tissue.

  2. 胞磷胆碱对大鼠脊髓损伤的神经保护性作用%Evaluation of the Neuroprotective Effects of Citicoline on Spinal Cord Injury of Rats

    Institute of Scientific and Technical Information of China (English)

    王威; 郭风劲; 廖苏平; 危蕾; 吴波; 刘俊; 徐卫国

    2012-01-01

    目的:观察胞磷胆碱对大鼠脊髓损伤(SCI)的神经保护作用.方法:成年SD大鼠72只随机分为对照组、甲基强的松龙(MP)组、胞磷胆碱组及联合组,各组18只;造模后即刻腹腔注射给药1次,对照组给予等量生理盐水,MP组给予30 mg/kg MP,胞磷胆碱组给予40 mg/kg胞磷胆碱,联合组给予30 mg/kg MP及40 mg/kg胞磷胆碱;伤后8、24及72 h每组各处死6只大鼠取材;HE染色观察脊髓组织的病理学变化,免疫组织化学方法观察半胱天冬氨酸酶(Caspase)-3和环氧化酶(COX)-2表达变化情况,DNA原位末端缺口标记法(TUNEL)检测神经细胞凋亡.结果:与对照组相比,MP组、胞磷胆碱组及联合组脊髓组织病理学改变明显减轻,Caspase-3和COX-2表达降低(P<0.05),凋亡细胞减少(P<0.05),MP组、胞磷胆碱组及联合组各组之间差异无统计学意义.结论:胞磷胆碱对大鼠SCI有神经保护性作用,与MP疗效相似,两者的联合应用与单独用药相比未见明显优势.%Objective: To investigate the neuroprotective effects of citicoline on spinal cord injury (SCI) of rats. Methods: Seventy-two adult SD rats were randomly divided into four groups (71=18 respectively): the control group (intraperitoneal injection of equal volume of normal sa line), the methylprednisolone (MP) group (intraperitoneal injection of 30 mg/kg MP) , the citi coline group (intraperitoneal injection of 40 mg/kg citicoline) and the combined treatment group (intraperitoneal injection of 30 mg/kg MP and 40 mg/kg citicoline). The rats were harvested at 8 h, 24 h, and 72 h (n=6 every time point) after SCI surgery. The tissue sections of the injured spinal cord were stained with hematoxylin and eosin (HE) to evaluate the histopathological chan ges. Immunohistochemistry was applied to detect the expressions of Caspase-3 and COX-2 while TUNEL staining was performed to evaluate the apoptosis of cells. Results: When compared with that in the control group, the

  3. The neuroprotective benefit from pioglitazone (PIO) addition on the alpha lipoic acid (ALA)-based treatment in experimental diabetic rats.

    Science.gov (United States)

    Jin, Heung Yong; Lee, Kyung Ae; Wu, Jin Zu; Baek, Hong Sun; Park, Tae Sun

    2014-12-01

    In this study, we investigated the combined effect of pioglitazone (PIO) with alpha lipoic acid (ALA) on the peripheral nerves of diabetic rats. Animals were divided into 8 groups (N = 6-8) and designated according to ALA (100 mg/kg/day) and PIO (10 mg/kg/day) treatment: Normal, Normal + ALA, Normal + PIO, Normal + ALA + PIO, DM, DM + ALA, DM + PIO, and DM + ALA + PIO. After 24 weeks, current perception threshold, mechanical allodynia, oxidative stresses, intraepidermal nerve fiber density (IENFD), and axonal morphology in the sciatic nerve were compared among groups. IENFD in the DM + ALA + PIO group was significantly less reduced than in other DM groups (7.61 ± 0.52 vs. 5.62 ± 0.96, 5.56 ± 0.60, and 7.10 ± 0.70 for DM, DM + ALA, and DM + PIO, respectively P diabetes. Moreover, PIO can be preferentially considered when additional glucose-lowering agent is required in DPN patients treated with ALA.

  4. Hypericum Perforatum Hydroalcoholic Extract Mitigates Motor Dysfunction and is Neuroprotective in Intrastriatal 6-Hydroxydopamine Rat Model of Parkinson's Disease.

    Science.gov (United States)

    Kiasalari, Zahra; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

    2016-05-01

    Parkinson's disease is the second most common neurodegenerative disorder with selective and progressive decline of nigral dopaminergic neurons. Hypericum perforatum L. (H. perforatum, St. John's wort) has been traditionally used for management of different disorders, especially mild-to-moderate depression. This study was conducted to evaluate the effect of H. perforatum extract against unilateral striatal 6-hydroxydopamine (6-OHDA) toxicity and to unmask some involved mechanisms. Intrastriatal 6-OHDA-lesioned rats were treated with H. perforatum hydroalcoholic extract at a dose of 200 mg/kg/day started 1 week pre-surgery for 1 week post-surgery. The extract attenuated apomorphine-induced rotational behavior, decreased the latency to initiate and the total time on the narrow beam task, lowered striatal level of malondialdehyde and enhanced striatal catalase activity and reduced glutathione content, normalized striatal expression of glial fibrillary acidic protein, tumor necrosis factor α with no significant effect on mitogen-activated protein kinase, lowered nigral DNA fragmentation, and prevented damage of nigral dopaminergic neurons with a higher striatal tyrosine hydroxylase immunoreactivity. These findings reveal the beneficial effect of H. perforatum via attenuation of DNA fragmentation, astrogliosis, inflammation, and oxidative stress.

  5. [Neuroprotective effects of the effective components group of xiaoshuantongluo against oxygen-glucose deprivation in primary cultured rat cortical neurons].

    Science.gov (United States)

    Xie, Xin-Mei; Pang, Xiao-Bin; Zhao, Yan; Wang, Bao-Quan; Chen, Ruo-Yun; Du, Guan-Hua

    2014-08-01

    This study is to investigate the effect of the effective components group of Xiaoshuantongluo (XECG) on neuronal injury induced by oxygen-glucose deprivation (OGD) in primary cortical cultures isolated from SD rat cortex at day 3 and the possible mechanism. Cells were divided into control group, OGD model group and XECG group (1, 3 and 10 mg x L(-1)). The cell viability was assessed with MTT assay and the LDH release rate was measured by enzyme label kit. The cell apoptosis was analyzed using Hoechst staining. RT-PCR was applied to detect the mRNA levels of JAK2 and STAT3. Western blotting was used to detect the expressions of Bcl-2, Bax, p-JAK2 and p-STAT3 proteins. Results showed that XECG resulted in an obvious resistance to oxygen-glucose deprivation-induced cell apoptosis and decrement of cell viability, decrease the cell LDH release rate. XECG could adjust the expression of Bcl-2 and Bax proteins and increase Bcl-2/Bax ratio, up-regulate the expression of p-JAK2 and p-STAT3. In conclusion, XECG could protect against the neuronal injury cells exposed to OGD, which may be relevant to the promotion of JAK2/STAT3 signaling pathway, and impact the expression of Bax and Bcl-2.

  6. Neuroprotective effects of quercetin on memory and anxiogenic-like behavior in diabetic rats: Role of ectonucleotidases and acetylcholinesterase activities.

    Science.gov (United States)

    Maciel, Roberto M; Carvalho, Fabiano B; Olabiyi, Ayodeji A; Schmatz, Roberta; Gutierres, Jessié M; Stefanello, Naiara; Zanini, Daniela; Rosa, Michelle M; Andrade, Cinthia M; Rubin, Maribel A; Schetinger, Maria Rosa; Morsch, Vera Maria; Danesi, Cristiane C; Lopes, Sonia T A

    2016-12-01

    The present study investigated the protective effect of quercetin (Querc) on memory, anxiety-like behavior and impairment of ectonucleotidases and acetylcholinesterase (AChE) activities in brain of streptozotocin-induced diabetic rats (STZ-diabetes). The type 1 diabetes mellitus was induced by an intraperitoneal injection of 70mg/kg of streptozotocin (STZ), diluted in 0.1M sodium-citrate buffer (pH 4.5). Querc was dissolved in 25% ethanol and administered by gavage at the doses of 5, 25 and 50mg/kg once a day during 40days. The animals were distributed in eight groups of ten animals as follows: vehicle, Querc 5mg/kg, Querc 25mg/kg, Querc 50mg/kg, diabetes, diabetes plus Querc 5mg/kg, diabetes plus Querc 25mg/kg and diabetes plus Querc 50mg/kg. Querc was able to prevent the impairment of memory and the anxiogenic-like behavior induced by STZ-diabetes. In addition, Querc prevents the decrease in the NTPDase and increase in the adenosine deaminase (ADA) activities in SN from cerebral cortex of STZ-diabetes. STZ-diabetes increased the AChE activity in SN from cerebral cortex and hippocampus. Querc 50mg/kg was more effective to prevent the increase in AChE activity in the brain of STZ-diabetes. Querc also prevented an increase in the malondialdehyde levels in all the brain structures. In conclusion, the present findings showed that Querc could prevent the impairment of the enzymes that regulate the purinergic and cholinergic extracellular signaling and improve the memory and anxiety-like behavior induced by STZ-diabetes.

  7. Behavioral effects of subchronic inhalation of toluene in adult rats.

    Science.gov (United States)

    Beasley, Tracey E; Evansky, Paul A; Gilbert, Mary E; Bushnell, Philip J

    2010-01-01

    Whereas the acute neurobehavioral effects of toluene are robust and well characterized, evidence for persistent effects of repeated exposure to this industrial solvent is less compelling. The present experiment sought to determine whether subchronic inhalation of toluene caused persistent behavioral changes in rats. Adult male Long-Evans rats inhaled toluene vapor (0, 10, 100, or 1000 ppm) for 6h/day, 5 days/week for 13 weeks and were evaluated on a series of behavioral tests beginning 3 days after the end of exposure. Toluene delayed appetitively-motivated acquisition of a lever-press response, but did not affect motor activity, anxiety-related behavior in the elevated plus maze, trace fear conditioning, acquisition of an appetitively-motivated visual discrimination, or performance of a visual signal detection task. Challenges with acute inhalation of toluene vapor (1200-2400 ppm for 1 h) and injections of quinpirole (0.01-0.03 mg/kg) and raclopride (0.03-0.10 mg/kg) revealed no toluene-induced latent impairments in visual signal detection. These results are consistent with a pattern of subtle and inconsistent long-term effects of daily exposure to toluene vapor, in contrast to robust and reliable effects of acute inhalation of the solvent.

  8. Neuroprotective effects of Wnt/β-catenin signaling pathway on intracra-nial hemorrhage in rats%Wnt/β-catenin通路对大鼠脑出血的保护作用

    Institute of Scientific and Technical Information of China (English)

    李治华; 陈曦; 臧卫东; 郭付有

    2015-01-01

    Aim:To investigate the neuroprotective effect of Wnt/β-catenin signaling pathway on intracranial hemor-rhage(ICH) in rats.Methods:A total of 96 adult SD rats were allocated into sham-operation group,ICH group,ICH+ve-hicle-treated group,and ICH+siDkk-1 group.The mRNA expressions of Wnt-1 and GSK-3βwere assessed by Real-time PCR at 24 and 72 h after ICH respectively .The expression of β-catenin was evaluated by Western blot analysis .Behavioral test was performed by the vibrissae-elicited forelimb-placing test in different groups .Results:There were remarkably down-regulated expression of Wnt-1 mRNA following ICH at 24 and 72 h, and the mRNA level of Wnt-1 was elevated after siDkk-1 administration(F=9.040 and 26.400, P<0.05).Increased GSK-3βmRNA expression was observed at 24 and 72 h af-ter ICH, and the mRNA level of GSK-3βwere reversed after siDkk-1 administration ( F =41.100 and 17.800, P <0.001).Western blot analysis showed that β-catenin protein was increased at 24 h and 72 h after ICH respectively, and the level of β-catenin was further up-regulated after being treated by siDkk-1 compared with ICH +vehicle-treated group (F=15.100 and 14.000, P<0.05).Meanwhile, decreased behavior scores regarding forelimb use asymmetry was found in the ICH group .However , the behavior scores regarding forelimb use asymmetry was improved after siDkk-1 administra-tion than those in the ICH+vehicle-treated group at 24 and 72 h after ICH(F=2 450.000 and 2 230.000, P<0.001). Conclusion:Wnt/β-catenin signaling pathway has neuroprotective effects against secondary brain injury following ICH , which may be associated with activation of Wnt-1, inhibition of GSK-3βresulting in β-catenin aggregation in the cyto-plasm,subsequent nuclear translocation and the downstream neuroprotective gene transcription .%目的:探讨Wnt/β-连环蛋白(β-catenin )通路对大鼠脑出血的保护作用机制。方法:96只成年SD雄性大鼠随机分为假手术组、脑出血组、

  9. Rubia cordifolia, Fagonia cretica linn and Tinospora cordifolia exert neuroprotection by modulating the antioxidant system in rat hippocampal slices subjected to oxygen glucose deprivation

    Directory of Open Access Journals (Sweden)

    Biswas Saibal K

    2004-08-01

    Full Text Available Abstract Background The major damaging factor during and after the ischemic/hypoxic insult is the generation of free radicals, which leads to apoptosis, necrosis and ultimately cell death. Rubia cordifolia (RC, Fagonia cretica linn (FC and Tinospora cordifolia (TC have been reported to contain a wide variety of antioxidants and have been in use in the eastern system of medicine for various disorders. However, their mechanism of action was largely unknown. We therefore selected these herbs for the present study to test their neuroprotective ability and the associated mechanism in rat hippocampal slices subjected to oxygen-glucose deprivation (OGD. Methods Hippocampal Slices were subjected to OGD (oxygen glucose deprivation and divided into 3 groups: control, OGD and OGD + drug treated. Cytosolic Cu-Zn superoxide dismutase (Cu-Zn SOD, reduced glutathione (GSH, glutathione peroxidase (GPx, nitric oxide (NO was measured as nitrite (NO2 in the supernatant and protein assays were performed in the respective groups at various time intervals. EPR was used to establish the antioxidant effect of RC, FC and TC with respect to superoxide anion (O2.-, hydroxyl radicals (. OH, nitric oxide (NO radical and peroxynitrite anion (ONOO generated from pyrogallol, menadione, DETA-NO and Sin-1 respectively. RT-PCR was performed for the three groups for GCLC, iNOS, Cu-Zn SOD and GAPDH gene expression. Results All the three herbs were effective in elevating the GSH levels, expression of the gamma-glutamylcysteine ligase and Cu-Zn SOD genes. The herbs also exhibited strong free radical scavenging properties against reactive oxygen and nitrogen species as studied by electron paramagnetic resonance spectroscopy. In addition all the three herbs significantly diminished the expression of iNOS gene after 48 hours which plays a major role in neuronal injury during hypoxia/ischemia. Conclusions RC, FC and TC therefore attenuate oxidative stress mediated cell injury during OGD

  10. Neonatal injections of methoxychlor decrease adult rat female reproductive behavior.

    Science.gov (United States)

    Bertolasio, Jennifer; Fyfe, Susanne; Snyder, Ben W; Davis, Aline M

    2011-12-01

    Methoxychlor (MXC), a commonly used pesticide, has been labeled as an endocrine disruptor. To evaluate the impact of neonatal exposure to MXC on female reproduction, female Sprague-Dawley rats were given subcutaneous injections on postnatal days 1, 3, and 5. The injections contained 1.0mg MXC, 2.0mg MXC, 10 μg 17β-estradiol benzoate (positive control), or sesame oil (vehicle). The injections of MXC had no effect on anogenital distance or day of vaginal opening. Treatment with either 2.0mg MXC or estradiol significantly increased the total number of days with vaginal keratinization. Treatment with MXC had no effect on ability to exhibit a mating response as an adult female, although the high dose MXC (2.0) and the positive control (estradiol) animals demonstrated a decrease in degree of receptivity, a decrease in proceptive behavior and an increase in rejection behavior. These data suggest that higher doses of MXC given directly to pups during the neonatal period can act as an estrogen and alter aspects of the nervous system, impacting adult reproductive characteristics.

  11. The proteome of neural stem cells from adult rat hippocampus

    Directory of Open Access Journals (Sweden)

    Fütterer Carsten D

    2003-06-01

    Full Text Available Abstract Background Hippocampal neural stem cells (HNSC play an important role in cerebral plasticity in the adult brain and may contribute to tissue repair in neurological disease. To describe their biological potential with regard to plasticity, proliferation, or differentiation, it is important to know the cellular composition of their proteins, subsumed by the term proteome. Results Here, we present for the first time a proteomic database for HNSC isolated from the brains of adult rats and cultured for 10 weeks. Cytosolic proteins were extracted and subjected to two-dimensional gel electrophoresis followed by protein identification through mass spectrometry, database search, and gel matching. We could map about 1141 ± 209 (N = 5 protein spots for each gel, of which 266 could be identified. We could group the identified proteins into several functional categories including metabolism, protein folding, energy metabolism and cellular respiration, as well as cytoskeleton, Ca2+ signaling pathways, cell cycle regulation, proteasome and protein degradation. We also found proteins belonging to detoxification, neurotransmitter metabolism, intracellular signaling pathways, and regulation of DNA transcription and RNA processing. Conclusions The HNSC proteome database is a useful inventory which will allow to specify changes in the cellular protein expression pattern due to specific activated or suppressed pathways during differentiation or proliferation of neural stem cells. Several proteins could be identified in the HNSC proteome which are related to differentiation and plasticity, indicating activated functional pathways. Moreover, we found a protein for which no expression has been described in brain cells before.

  12. Primary culture of adult rat liver cells. I. Preparation of isolated cells from trypsin-perfused liver of adult rat

    Directory of Open Access Journals (Sweden)

    Miyazaki,Masahiro

    1977-12-01

    Full Text Available Isolated hepatic cells from adult rats were prepared by perfusing the livers with trypsin. The highest yield of viable cells was obtained by perfusing the liver with 0.1% trypsin, pH 7.0, at 37 degrees C for 30 min. Following this treatment about 70% of cells excluded trypan blue. The isolated cells contained many binucleate cells. Between 60 and 70% of DNA present originally in the liver was recovered from the isolated hepatic cells, which had higher glucose 6-phosphatase activity than the liver. Thus the resulting cell population seems to be rich in hepatocytes. The isolated hepatic cells, however, lost some of their cellular proteins such as alanine and tyrosine amino-transferases. It was suggested that the membranes of isolated hepatic cells might be damaged by both enzymatic digestion and mechanical destruction.

  13. Neuroprotective efficacy of a proneurogenic compound after traumatic brain injury.

    Science.gov (United States)

    Blaya, Meghan O; Bramlett, Helen M; Naidoo, Jacinth; Pieper, Andrew A; Dietrich, W Dalton

    2014-03-01

    Traumatic brain injury (TBI) is characterized by histopathological damage and long-term sensorimotor and cognitive dysfunction. Recent studies have reported the discovery of the P7C3 class of aminopropyl carbazole agents with potent neuroprotective properties for both newborn neural precursor cells in the adult hippocampus and mature neurons in other regions of the central nervous system. This study tested, for the first time, whether the highly active P7C3-A20 compound would be neuroprotective, promote hippocampal neurogenesis, and improve functional outcomes after experimental TBI. Sprague-Dawley rats subjected to moderate fluid percussion brain injury were evaluated for quantitative immunohistochemical and behavioral changes after trauma. P7C3-A20 (10 mg/kg) or vehicle was initiated intraperitoneally 30 min postsurgery and twice per day every day thereafter for 7 days. Administration of P7C3-A20 significantly reduced overall contusion volume, preserved vulnerable anti-neuronal nuclei (NeuN)-positive pericontusional cortical neurons, and improved sensorimotor function 1 week after trauma. P7C3-A20 treatment also significantly increased both bromodeoxyuridine (BrdU)- and doublecortin (DCX)-positive cells within the subgranular zone of the ipsilateral dentate gyrus 1 week after TBI. Five weeks after TBI, animals treated with P7C3-A20 showed significantly increased BrdU/NeuN double-labeled neurons and improved cognitive function in the Morris water maze, compared to TBI-control animals. These results suggest that P7C3-A20 is neuroprotective and promotes endogenous reparative strategies after TBI. We propose that the chemical scaffold represented by P7C3-A20 provides a basis for optimizing and advancing new pharmacological agents for protecting patients against the early and chronic consequences of TBI.

  14. Passive immunization with LINGO-1 polyclonal antiserum afforded neuroprotection and promoted functional recovery in a rat model of spinal cord injury.

    Science.gov (United States)

    Lv, Jun; Xu, Ru-xiang; Jiang, Xiao-dan; Lu, Xin; Ke, Yi-quan; Cai, Ying-qian; Du, Mou-xuan; Hu, Changchen; Zou, Yu-xi; Qin, Ling-sha; Zeng, Yan-jun

    2010-01-01

    LINGO-1 (leucine-rich repeat and Ig domain-containing, Nogo receptor-interacting protein) is an important component of the NgR receptor complex involved in RhoA activation and axon regeneration. The authors report on passive immunization with LINGO-1 polyclonal antiserum, a therapeutic approach to overcome NgR-mediated growth inhibition after spinal cord injury (SCI). The intrathecally administered high-titer rabbit-derived antiserum can be detected around the injury site within a wide time window; it blocks LINGO-1 in vivo with high molecular specificity. In this animal model, passive immunization with LINGO-1 antiserum significantly decreased RhoA activation and increased neuronal survival. Adult rats immunized in this manner show recovery of certain hindlimb motor functions after dorsal hemisection of the spinal cord. Thus, passive immunotherapy with LINGO-1 polyclonal antiserum may represent a promising repair strategy following acute SCI.

  15. PREPUBERTAL EXPOSURES TO COMPOUNDS THAT INCREASE PROLACTIN SECRETION IN THE MALE RAT: EFFECTS ON ADULT PROSTATE

    Science.gov (United States)

    Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate.Stoker TE, Robinette CL, Britt BH, Laws SC, Cooper RL.Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effec...

  16. Transformation of adult rat cardiac myocytes in primary culture.

    Science.gov (United States)

    Banyasz, Tamas; Lozinskiy, Ilya; Payne, Charles E; Edelmann, Stephanie; Norton, Byron; Chen, Biyi; Chen-Izu, Ye; Izu, Leighton T; Balke, C William

    2008-03-01

    We characterized the morphological, electrical and mechanical alterations of cardiomyocytes in long-term cell culture. Morphometric parameters, sarcomere length, T-tubule density, cell capacitance, L-type calcium current (I(Ca,L)), inward rectifier potassium current (I(K1)), cytosolic calcium transients, action potential and contractile parameters of adult rat ventricular myocytes were determined on each day of 5 days in culture. We also analysed the health of the myocytes using an apoptotic/necrotic viability assay. The data show that myocytes undergo profound morphological and functional changes during culture. We observed a progressive reduction in the cell area (from 2502 +/- 70 microm(2) on day 0 to 1432 +/- 50 microm(2) on day 5), T-tubule density, systolic shortening (from 0.11 +/- 0.02 to 0.05 +/- 0.01 microm) and amplitude of calcium transients (from 1.54 +/- 0.19 to 0.67 +/- 0.19) over 5 days of culture. The negative force-frequency relationship, characteristic of rat myocardium, was maintained during the first 2 days but diminished thereafter. Cell capacitance (from 156 +/- 8 to 105 +/- 11 pF) and membrane currents were also reduced (I(Ca,L), from 3.98 +/- 0.39 to 2.12 +/- 0.37 pA pF; and I(K1), from 34.34p +/- 2.31 to 18.00 +/- 5.97 pA pF(-1)). We observed progressive depolarization of the resting membrane potential during culture (from 77.3 +/- 2.5 to 34.2 +/- 5.9 mV) and, consequently, action potential morphology was profoundly altered as well. The results of the viability assays indicate that these alterations could not be attributed to either apoptosis or necrosis but are rather an adaptation to the culture conditions over time.

  17. Influences of olfactory ensheathing cells transplantation on axonal regeneration in spinal cord of adult rats

    Institute of Scientific and Technical Information of China (English)

    沈慧勇; 唐勇; 吴燕峰; 陈燕涛; 程志安

    2002-01-01

    To observe whether olfactory ensheathing cells could be used to promote axonal regeneration in a spontaneously nonregenerating system. Methods: After laminectomy at the lower thoracic level, the spinal cords of adult rats were exposed and completely transected at T10. A suspension of ensheathing cells was injected into the lesion site in 12 adult rats, and control D/F-12 (1∶1 mixture of DMEM and Hams F-12) was injected in 12 adult rats. Six weeks and ten weeks after cell transplantation, the rats were evaluated by climbing test and motor evoked potentials (MEPs) monitoring. The samples were procured and studied with histologicl and immunohistochemical methods. Results: At the 6th week after cell transplantation, all the rats in both the transplanted and control groups were paraplegic and the MEPs could not be recorded. At the 10th week after cell transplantation, of 7 rats in the control group, 2 rats had muscles contraction of the lower extremities, 2 rats had hips and/or knees active movement; and 5 rats MEPs could be recorded in the hind limbs in the transplanted group (n=7). None of the rats in the control group had functional improvement and no MEPs recorded (n=7). Numerous regenerating axons were observed through the transplantation and continued to regenerate into the denervated host tract. Cell labelling using anti-Myelin Basic Protein (MBP) and anti-Nerve Growth Factor Receptor (anti-NGFR) indicated that the regenerated axons were derived from the appropriate neuronal source and that donor cells migrated into the denervated host tract. But axonal degeneration existed and regenerating axons were not observed within the spinal cords of the adult rats with only D/F-12 injection. Conclusions: The axonal regeneration in the transected adult rat spinal cord is possible after ensheathing cells transplantation.

  18. Tooth movement characteristics in relation to root resorption in young and adult rats

    NARCIS (Netherlands)

    Ren, Yijin; Maltha, Jaap C.; Kuijpers-Jagtman, Anne Marie

    2007-01-01

    The aim of this study was to investigate tooth movement characteristics in relation to root resorption in young and adult rats. Two groups of 30 rats each (aged 6 wk and 9-12 months, respectively) were used. Standardized orthodontic appliances were placed to move the maxillary molars mesially. Anima

  19. Neuregulins, Neuroprotection and Parkinson’s Disease

    Science.gov (United States)

    2006-09-01

    cultures. Journal of Neurochemistry 91: 1358-1368. Yurek, D.M., Zhang, L., Fletcher-Turner, A. and Seroogy, K.B. (2004) Supranigral injection of...speaker, Central Ohio Parkinson Society, Annual Symposium, Columbus, OH, April 24, 2004) 8 “Neuroprotective and Neurotrophic Actions of Neuregulin...growth factor-2 on dopaminergic neurons in rat primary midbrain cultures. Journal of Neurochemistry 91: 1358-1368. Yurek, D.M., Zhang, L., Fletcher

  20. Neuroprotection of rat hippocampal slices exposed to oxygen-glucose deprivation by enrichment with docosahexaenoic acid and by inhibition of hydrolysis of docosahexaenoic acid-containing phospholipids by calcium independent phospholipase A2.

    Science.gov (United States)

    Strokin, M; Chechneva, O; Reymann, K G; Reiser, G

    2006-06-30

    Polyunsaturated fatty acids play an important role in the development of pathological states in brain after hypoxia/ischemia. Here, we investigated the role of docosahexaenoic acid (22:6n-3) in brain phospholipids for neuronal survival. We used organotypic cultures of rat brain hippocampal slices exposed to 40 min of oxygen-glucose deprivation, to study the consequences of experimental ischemia. In [14C]docosahexaenoic acid-labeled cultures, oxygen-glucose deprivation induced significant release of radioactive docosahexaenoic acid. This release could be blocked by the selective inhibitor of the Ca2+-independent phospholipase A2, 4-bromoenol lactone (10 microM), when it was added 30 min prior to oxygen-glucose deprivation. Addition of 4-bromoenol lactone at 30 min prior to oxygen-glucose deprivation markedly decreased the neuronal damage induced by oxygen-glucose deprivation. The protective effect was substantially higher in dentate gyrus than in CA1 and CA3 areas. Enrichment of the hippocampal tissue with docosahexaenoic acid by incubation with 10 microM docosahexaenoic acid for 24 h exerted the same neuroprotective effect, which was observed after treatment with 4-bromoenol lactone. In contrast to the 24 h-preincubation, simultaneous addition of docosahexaenoic acid with the onset of oxygen-glucose deprivation had no protective effect. This suggests that incorporation of docosahexaenoic acid into phospholipids is required for the protective effect observed. Then the possible involvement of arachidonic acid metabolism in docosahexaenoic acid-induced neuroprotection was tested. Inhibition of prostaglandin production by ibuprofen produced no change in neuroprotection after 24-h incubation of the hippocampal slices with docosahexaenoic acid. Simultaneous inhibition of Ca2+-independent and Ca2+-dependent phospholipases A2 by treatment with the general phospholipase A2 inhibitor methyl arachidonyl fluorophosphonate (3 microM, 30 min prior to oxygen-glucose deprivation

  1. Adolescent and adult male spontaneous hyperactive rats (SHR) respond differently to acute and chronic methylphenidate (Ritalin).

    Science.gov (United States)

    Barron, Elyssa; Yang, Pamela B; Swann, Alan C; Dafny, Nachum

    2009-01-01

    Eight groups of male adolescent and adult spontaneous hyperactive rats (SHR) were used in a dose response (saline, 0.6, 2.5, and 10 mg/kg) experiment of methylphenidate (MPD). Four different locomotor indices were recorded for 2 hours postinjection using a computerized monitoring system. Acutely, the 0.6 mg/kg dose of MPD did not elicit an increase in locomotor activity in either the adolescent or in the adult male SHR. The 2.5 and the 10.0 mg/kg doses increased activity in the adolescent and the adult rats. Chronically, MPD treatment when comparing adolescent and adult gave the following results: the 0.6 mg/kg dose of MPD failed to cause sensitization in the adolescent group but caused sensitization in the adult group, while the 2.5 and 10 mg/kg both caused sensitization in the adolescent and adult groups.

  2. Prenatal exposure to ethanol causes partial diabetes insipidus in adult rats.

    Science.gov (United States)

    Knee, Daniel S; Sato, Aileen K; Uyehara, Catherine F T; Claybaugh, John R

    2004-08-01

    Chronic consumption of ethanol in adult rats and humans leads to reduced AVP-producing neurons, and prenatal ethanol (PE) exposure has been reported to cause changes in the morphology of AVP-producing cells in the suprachiasmatic nucleus of young rats. The present studies further characterize the effects of PE exposure on AVP in the young adult rat, its hypothalamic synthesis, pituitary storage, and osmotically stimulated release. Pregnant rats were fed a liquid diet with 35% of the calories from ethanol or a control liquid diet for days 7-22 of pregnancy. Water consumption and urine excretion rate were measured in the offspring at 60-68 days of age. Subsequently, the offspring were infused with 5% NaCl at 0.05 ml.kg(-1).min(-1) with plasma samples taken before and at three 40-min intervals during infusion for measurement of AVP and osmolality. Urine output and water intake were approximately 20% greater in PE-exposed rats than in rats with no PE exposure, and female rats had a greater water intake than males. The relationship between plasma osmolality and AVP in PE-exposed rats was parallel to, but shifted to the right of, the control rats, indicating an increase in osmotic threshold for AVP release. Pituitary AVP was reduced by 13% and hypothalamic AVP mRNA content was reduced by 35% in PE-exposed rats. Our data suggest that PE exposure can cause a permanent condition of a mild partial central diabetes insipidus.

  3. Enhanced neuroprotection and improved motor function in traumatized rat spinal cords by rAAV2-mediated Glial-derived neurotrophic factor combined with early rehabilitation training

    Institute of Scientific and Technical Information of China (English)

    Han Qingquan; Xiang Jingjing; Zhang Yun; Qiao Hujun; Shen Yongwei; Zhang Chun

    2014-01-01

    Background Spinal cord injury (SCI) is a serious neurological injury that often leads to permanent disabilities for the victims.The aim of this study was to determine the effects of glial-derived neurotrophic factor (GDNF) mediated by recombinant adeno-associated virus type 2 (rAAV2) alone or in combination with early rehabilitation training on SCI.Methods SCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats.Then besides the sham operation group,the SCI rats were randomly divided into four groups:natural healing group,gene therapy group,rehabilitation training group,and combination therapy group (gene therapy in combination with rehabilitation training).Motor dysfunction,protein expression of GDNF,edema formation,and cell injury were examined 7,14,and 21 days after trauma.Results The topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF,especially after the 14th day,and could protect the motor neuron ceils.Early rehabilitative treatment resulted in significantly improved motor function,reduced edema formation,and protected the cells from injury,especially after the 7th and 14th days,and increased the GDNF expression in the damaged area,which was most evident after Day 14.The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days.Conclusion These observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.

  4. HAIR CELL-LIKE CELL GENERATION INDUCED BY NATURE CULTURE OF ADULT RAT AUDITORY EPITHELIUM

    Institute of Scientific and Technical Information of China (English)

    Liu Hui; Zhu Hongliang; Li Shengli; Yao Xiaobao; Wang Xiaoxia

    2006-01-01

    Objective To establish adult rat auditory epithelial cell culture and try to find precursor cells of auditory hair cells in vitro. Methods With refinement of culture media and techniques, cochlear sensory epithelial cells of adult rat were cultured. Immunocytochemistry and Bromodeoxyuridine (BrdU)labeling were used to detect properties and mitotic status of cultured cells. Results The cultured auditory epithelial cells showed a large, flat epithelial morphotype and expressed F-actin and cytokeratin, a subset of cells generated from auditory epithelium were labeled by calretinin, a specific marker of early hair cell. Conclusion Adult rat auditory epithelium can be induced to generate hair cell-like cells by nature culture, this phenomenon suggests that progenitor cells may exist in rat cochlea and they may give birth to new hair cells. Whether these progenitor cells are tissue specific stem cells is still need more study.

  5. Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells

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    Hua Wang

    2015-01-01

    Full Text Available Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic nerve. However, it remains unclear regarding the effects of Lycium barbarum polysaccharides, the main component of Lycium barbarum, on in vivo proliferation of adult ciliary body cells. In this study, adult rats were intragastrically administered low- and high-dose Lycium barbarum polysaccharides (1 and 10 mg/kg for 35 days and those intragastrically administered phosphate buffered saline served as controls. The number of Ki-67-positive cells in rat ciliary body in the Lycium barbarum polysaccharides groups, in particular low-dose Lycium barbarum polysaccharides group, was significantly greater than that in the phosphate buffered saline group. Ki-67-positive rat ciliary body cells expressed nestin but they did not express glial fibrillary acidic protein. These findings suggest that Lycium barbarum polysaccharides can promote the proliferation of adult rat retinal progenitor cells and the proliferated cells present with neuronal phenotype.

  6. Effects of acute adult and early-in-life bladder inflammation on bladder neuropeptides in adult female rats

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    Ness Timothy J

    2011-08-01

    Full Text Available Abstract Background The purpose of the present study was to determine how acute adult and/or prior early-in life (EIL; P14-P16 exposure to bladder inflammation affects bladder content of calcitonin gene related peptide (CGRP and substance P (SP. Estrous cycle influences were also studied in the adult-treatment conditions. Methods In Experiment 1, intravesical zymosan or isoflurane anesthesia alone was administered to adult female rats. Bladders and serum were collected 24 hours later during each phase of the estrous cycle. In Experiment 2, zymosan or anesthesia alone was administered EIL and as adults, with bladder tissue collection 24 h later. Results In general, Experiment 1 showed that bladder content of both CGRP and SP was increased by inflammation. This effect was significant when data were collapsed across all phases of the estrous cycle, but was only significant during proestrus when individual comparisons were made during each phase of estrous. Also, adult bladder inflammation significantly reduced estradiol levels. In Experiment 2, bladder content of CGRP and SP was significantly increased in rats receiving EIL and/or adult inflammation. Bladder weights were also significantly increased by inflammation. Conclusions These data indicate that bladder CGRP and SP are maximally increased during the proestrus phase of the estrous cycle in inflamed adult female rats. EIL exposure to bladder inflammation alone can also produce an increase in CGRP and SP lasting into adulthood. Therefore, EIL experience with bladder inflammation may predispose an organism to experience a painful bladder disorder as an adult by increasing primary afferent content of CGRP and/or SP.

  7. Neuroprotection in glaucoma

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    Azadeh Doozandeh

    2016-01-01

    Full Text Available Glaucoma is a degenerative optic neuropathy characterized by retinal ganglion cell (RGC loss and visual field defects. It is known that in some glaucoma patients, death of RGCs continues despite intraocular pressure (IOP reduction. Neuroprotection in the field of glaucoma is defined as any treatment, independent of IOP reduction, which prevents RGC death. Glutamate antagonists, ginkgo biloba extract, neurotrophic factors, antioxidants, calcium channel blockers, brimonidine, glaucoma medications with blood regulatory effect and nitric oxide synthase inhibitors are among compounds with possible neuroprotective activity in preclinical studies. A few agents (such as brimonidine or memantine with neuroprotective effects in experimental studies have advanced to clinical trials; however the results of clinical trials for these agents have not been conclusive. Nevertheless, lack of compelling clinical evidence has not prevented the off-label use of some of these compounds in glaucoma practice. Stem cell transplantation has been reported to halt experimental neurodegenerative disease processes in the absence of cell replacement. It has been hypothesized that transplantation of some types of stem cells activates multiple neuroprotective pathways via secretion of various factors. The advantage of this approach is a prolonged and targeted effect. Important concerns in this field include the secretion of unwanted harmful mediators, graft survival issues and tumorigenesis. Neuroprotection in glaucoma, pharmacologically or by stem cell transplantation, is an interesting subject waiting for broad and multidisciplinary collaborative studies to better clarify its role in clinical practice.

  8. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil. Electrophysiological...

  9. Is longer sevoflurane preconditioning neuroprotective in permanent focal cerebral ischemia?

    Institute of Scientific and Technical Information of China (English)

    Caiwei Qiu; Bo Sheng; Shurong Wang; Jin Liu

    2013-01-01

    Sevoflurane preconditioning has neuroprotective effects in the cerebral ischemia/reperfusion model. However, its influence on permanent cerebral ischemia remains unclear. In the present study, the rats were exposed to sevoflurane for 15, 30, 60, and 120 minutes, fol owed by induction of perma-nent cerebral ischemia. Results demonstrated that 30-and 60-minute sevoflurane preconditioning significantly reduced the infarct volume at 24 hours after cerebral ischemia, and 60-minute lurane preconditioning additional y reduced the number of TUNEL-and caspase-3-positive cel s in the ischemic penumbra. However, 120-minute sevoflurane preconditioning did not show evident neuroprotective effects. Moreover, 60-minute sevoflurane preconditioning significantly attenuated neurological deficits and infarct volume in rats at 4 days after cerebral ischemia. These findings in-dicated that 60-minute sevoflurane preconditioning can induce the best neuroprotective effects in rats with permanent cerebral ischemia through the inhibition of apoptosis.

  10. Taurine provides neuroprotection against retinal ganglion cell degeneration.

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    Nicolas Froger

    Full Text Available Retinal ganglion cell (RGC degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats. After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%, whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases.

  11. Taurine provides neuroprotection against retinal ganglion cell degeneration.

    Science.gov (United States)

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases.

  12. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    Science.gov (United States)

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  13. Influence of rat substrain and growth conditions on the characteristics of primary cultures of adult rat spinal cord astrocytes.

    Science.gov (United States)

    Codeluppi, Simone; Gregory, Ebba Norsted; Kjell, Jacob; Wigerblad, Gustaf; Olson, Lars; Svensson, Camilla I

    2011-04-15

    Primary astrocyte cell cultures have become a valuable tool for studies of signaling pathways that regulate astrocyte physiology, reactivity, and function; however, differences in culture preparation affect data reproducibility. The aim of this work was to define optimal conditions for obtaining primary astrocytes from adult rat spinal cord with an expression profile most similar to adult human spinal cord astrocytes. Hence, we examined whether different Sprague-Dawley substrains and culture conditions affect astrocyte culture quality. Medium supplemented with fetal bovine serum from three sources (Sigma, Gibco, Hyclone) or a medium with defined composition (AM medium) was used to culture astrocytes isolated from spinal cords of adult Harlan and Charles River Spraque-Dawley rats. Purity was significantly different between cultures established in media with different sera. No microglia were detected in AM or Hyclone cultures. Gene expression was also affected, with AM cultures expressing the highest level of glutamine synthetase, connexin-43, and glutamate transporter-1. Interestingly, cell response to starvation was substrain dependent. Charles River-derived cultures responded the least, while astrocytes derived from Harlan rats showed a greater decrease in Gfap and glutamine synthetase, suggesting a more quiescent phenotype. Human and Harlan astrocytes cultured in AM media responded similarly to starvation. Taken together, this study shows that rat substrain and growth medium composition affect purity, expression profile and response to starvation of primary astrocytes suggesting that cultures of Harlan rats in AM media have optimal astrocyte characteristics, purity, and similarity to human astrocytes.

  14. The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

    Science.gov (United States)

    Ornelas, Laura C; Novier, Adelle; Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-03-01

    Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months) male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a separate group of animals, blood ethanol concentrations (BEC) were determined at multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests were conducted with a Latin square repeated-measures design in which all animals received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3 separate sessions via intraperitoneal (i.p.) injection. During testing, motor impairments were assessed on the RR 10 min post-injection and on ARR 20 min post-injection. Aged animals spent significantly less time on the RR when administered 1.0 g/kg alcohol compared to adult rats. In addition, motor performance impairments significantly increased with age after 2.0 g/kg alcohol administration. On the ARR test, aged rats were more sensitive to the effects of 1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days after the last testing session, animals were given 3.0 g/kg alcohol and LORR was examined. During LORR, aged animals slept longer compared to adult and adolescent rats. This effect cannot be explained solely by BEC levels in aged rats. The present study suggests that acute alcohol exposure produces greater motor impairments in older rats when compared to adolescent and adult rats and begins to establish a

  15. Effects of voluntary physical exercise, citicoline, and combined treatment on object recognition memory, neurogenesis, and neuroprotection after traumatic brain injury in rats.

    Science.gov (United States)

    Jacotte-Simancas, Alejandra; Costa-Miserachs, David; Coll-Andreu, Margalida; Torras-Garcia, Meritxell; Borlongan, Cesar V; Portell-Cortés, Isabel

    2015-05-15

    The biochemical and cellular events that lead to secondary neural damage after traumatic brain injury (TBI) contribute to long-term disabilities, including memory deficits. There is a need to search for single and/or combined treatments aimed at reducing these TBI-related disfunctions. The effects of citicoline and of voluntary physical exercise in a running wheel (3 weeks), alone or in combination, on TBI-related short-term (3 h) and long-term (24 h) object recognition memory (ORM) deficits and on neurogenesis and neuroprotection were examined using a rodent model of TBI (controlled cortical impact injury). Citicoline improved memory deficits at the two times tested, while physical exercise only in the long-term test. Physical exercise had a clear neuroprotective effect as indicated by reduced interhemispheric differences in hippocampal formation and lateral ventricle volumes and in density of mature neurons in the hilus of the dentate gyrus and the perirhinal cortex. Physical exercise also increased cell proliferation and neurogenesis in the granular cell layer of the dentate gyrus. Some degree of neuroprotection of citicoline was suggested by reduced interhemispheric differences in the volume of the hippocampal formation. Contrary to what was expected, the effects of citicoline and physical exercise did not sum up. Further, a negative interference between both treatments was found in several behavioral and histological variables. The promising profiles of both treatments as therapeutic tools in TBI when applied singly underscore the need to perform further works looking for other combined treatment regimens that increase the benefit of each treatment alone.

  16. Effects of neonatal overfeeding on juvenile and adult feeding and energy expenditure in the rat.

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    Aneta Stefanidis

    Full Text Available Overfeeding during perinatal life leads to an overweight phenotype that persists throughout the juvenile stage and into adulthood, however, the mechanism(s underlying this effect are poorly understood. We hypothesized that obesity due to neonatal overfeeding is maintained by changes in energy expenditure and that these changes differ between males and females. We investigated feeding, physical activity, hormonal and metabolic alterations that occur in adult rats made obese by having been nursed in small litters (SL compared with those from control litters (CL. There were no differences in absolute food intake between the groups, and juvenile and adult SL rats ate less chow per gram body weight than the CL did in the dark (active phase. Juvenile, but not adult SL rats did have reduced whole body energy expenditure, but there were no differences between the groups by the time they reached adulthood. Adult SL females (but not males had reduced brown adipose tissue (BAT temperatures compared with CL in the first half of the dark phase. Our results indicate a persistent overweight phenotype in rats overfed as neonates is not associated with hyperphagia at any stage, but is reflected in reduced energy expenditure into the juvenile phase. The reduced dark phase BAT activity in adult SL females is not sufficient to reduce total energy expenditure at this stage of life and there is an apparently compensatory effect that prevents SL and CL from continuing to diverge in weight that appears between the juvenile and adult stages.

  17. The neuroprotective mechanism of brain ischemic preconditioning

    Institute of Scientific and Technical Information of China (English)

    Xiao-qian LIU; Rui SHENG; Zheng-hong QIN

    2009-01-01

    Brain ischemia is one of the most common causes of death and the leading cause of adult disability in the world. Brain ischemic pre- conditioning (BIP) refers to a transient, sublethal ischemia which results in tolerance to later, otherwise lethal, cerebral ischemia. Many attempts have been made to understand the molecular and cellular mechanisms underlying the neuroprotection offered by ischemic preconditioning. Many studies have shown that neuroprotective mechanisms may involve a series of molecular regulatory pathways including activation of the N-methyI-D-aspartate (NMDA) and adenosine receptors; activation of intracellular signaling pathways such as mitogen activated protein kinases (MAPK) and other protein kinases; upregulation of Bcl-2 and heat shock proteins (HSPs); and activation of the ubiquitin-proteasome pathway and the autophagic-lysosomal pathway. A better understanding of the processes that lead to cell death after stroke as well as of the endogenous neuroprotective mechanisms by which BIP protects against brain ischemic insults could help to develop new therapeutic strategies for this devastating neurological disease. The purpose of the present review is to summarize the neuroprotective mechanisms of BIP and to discuss the possibility of mimicking ischemic preconditioning as a new strategy for preventive treatment of ischemia.

  18. Differentiation of embryonic versus adult rat neural stem cells into dopaminergic neurons in vitro

    Institute of Scientific and Technical Information of China (English)

    Chunlong Ke; Baili Chen; Shaolei Guo; Chao Yang

    2008-01-01

    BACKGROUND: It has been reported that the conversion of neural stem cells into dopaminergic neurons in vitro can be increased through specific cytokine combinations. Such neural stem cell-derived dopaminergic neurons could be used for the treatment of Parkinson's disease. However, little is known about the differences in dopaminergic differentiation between neural stem cells derived from adult and embryonic rats.OBJECTIVE: To study the ability of rat adult and embryonic-derived neural stem cells to differentiate into dopaminergic neurons in vitro.DESIGN: Randomized grouping design.SETTING: Department of Neurosurgery in the First Affiliated Hospital of Sun Yat-sen University.MATERIALS: This experiment was performed at the Surgical Laboratory in the First Affiliated Hospital of Sun Yat-scn University (Guangzhou, Guangdong, China) from June to December 2007. Eight, adult, male,Sprague Dawley rats and eight, pregnant, Sprague Dawley rats (embryonic day 14 or 15) were provided by the Experimental Animal Center of Sun Yat-sen University.METHODS: Neural stem cells derived from adult and embryonic rats were respectively cultivated in serum-free culture medium containing epidermal growth factor and basic fibroblast growth factor. After passaging, neural stem cells were differentiated in medium containing interleukin-1 ct, interleukin-11, human leukemia inhibition factor, and glial cell line-derived neurotrophic factor. Six days later, cells were analyzed by immunocytochemistry and flow cytometry.MAIN OUTCOME MEASURES: Alterations in cellular morphology after differentiation of neural stem cells derived from adult and embryonic rats; and percentage of tyrosine hydroxylase-positive neurons in the differentiated cells.RESULTS: Neural stem cells derived from adult and embryonic rats were cultivated in differentiation medium. Six days later, differentiated cells were immunoreactive for tyrosine hydroxylasc. The percentage of tyrosine hydroxylase positive neurons was (5.6 ± 2

  19. Statins: Mechanisms of neuroprotection

    NARCIS (Netherlands)

    van der Most, Peter J.; Dolga, Amalia; Nijholt, Ingrid M.; Luiten, Paul G. M.; Eisel, Ulrich L. M.

    2009-01-01

    Clinical trials report that the class of drugs known as statins may be neuroprotective in Alzheimer's and Parkinson's disease, and further trials are currently underway to test whether these drugs are also beneficial in multiple sclerosis and acute stroke treatment. Since statins are well tolerated

  20. Statins : Mechanisms of neuroprotection

    NARCIS (Netherlands)

    van der Most, Peter J; Dolga, Amalia M; Nijholt, Ingrid M; Luiten, Paul G.; Eisel, Ulrich L M

    2009-01-01

    Clinical trials report that the class of drugs known as statins may be neuroprotective in Alzheimer's and Parkinson's disease, and further trials are currently underway to test whether these drugs are also beneficial in multiple sclerosis and acute stroke treatment. Since statins are well tolerated

  1. Neuroprotective effects of Asiaticoside.

    Science.gov (United States)

    Qi, Feng-Yan; Yang, Le; Tian, Zhen; Zhao, Ming-Gao; Liu, Shui-Bing; An, Jia-Ze

    2014-07-01

    In the central nervous system, Asiaticoside has been shown to attenuate in vitro neuronal damage caused by exposure to β-amyloid. In vivo studies demonstrated that Asiaticoside could attenuate neurobehavioral, neurochemical and histological changes in transient focal middle cerebral artery occlusion animals. In addition, Asiaticoside showed anxiolytic effects in acute and chronic stress animals. However, its potential neuroprotective properties in glutamate-induced excitotoxicity have not been fully studied. We investigated the neuroprotective effects of Asiaticoside in primary cultured mouse cortical neurons exposed to glutamate-induced excitotoxicity invoked by N-methyl-D-aspartate. Pretreatment with Asiaticoside decreased neuronal cell loss in a concentration-dependent manner and restored changes in expression of apoptotic-related proteins Bcl-2 and Bax. Asiaticoside pretreatment also attenuated the upregulation of NR2B expression, a subunit of N-methyl-D-aspartate receptors, but did not affect expression of NR2A subunits. Additionally, in cultured neurons, Asiaticoside significantly inhibited Ca(2+) influx induced by N-methyl-D-aspartate. These experimental findings provide preliminary evidence that during excitotoxicity induced by N-methyl-D-aspartate exposure in cultured cortical neurons, the neuroprotective effects of Asiaticoside are mediated through inhibition of calcium influx. Aside from its anti-oxidant activity, down-regulation of NR2B-containing N-methyl-D-aspartate receptors may be one of the underlying mechanisms in Asiaticoside neuroprotection.

  2. Astaxanthin rescues neuron loss and attenuates oxidative stress induced by amygdala kindling in adult rat hippocampus.

    Science.gov (United States)

    Lu, Yan; Xie, Tao; He, Xue-Xin; Mao, Zhuo-Feng; Jia, Li-Jing; Wang, Wei-Ping; Zhen, Jun-Li; Liu, Liang-Min

    2015-06-15

    Oxidative stress plays an important role in the neuronal damage induced by epilepsy. The present study assessed the possible neuroprotective effects of astaxanthin (ATX) on neuronal damage, in hippocampal CA3 neurons following amygdala kindling. Male Sprague-Dawley rats were chronically kindled in the amygdala and ATX or equal volume of vehicle was given by intraperitoneally. Twenty-four hours after the last stimulation, the rats were sacrificed by decapitation. Histopathological changes and the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and reduced glutathione (GSH) were measured, cytosolic cytochrome c (CytC) and caspase-3 activities in the hippocampus were also recorded. We found extensive neuronal damage in the CA3 region in the kindling group, which was preceded by increases of ROS level and MDA concentration and was followed by caspase-3 activation and an increase in cytosolic CytC. Treatment with ATX markedly attenuated the neuronal damage. In addition, ATX significantly decreased ROS and MDA concentrations and increased GSH levels. Moreover, ATX suppressed the translation of CytC release and caspase-3 activation in hippocampus. Together, these results suggest that ATX protects against neuronal loss due to epilepsy in the rat hippocampus by attenuating oxidative damage, lipid peroxidation and inhibiting the mitochondrion-related apoptotic pathway.

  3. A Pilot Study for the Neuroprotective Effect of Gongjin-dan on Transient Middle Cerebral Artery Occlusion-Induced Ischemic Rat Brain

    Directory of Open Access Journals (Sweden)

    Yun-Young Sunwoo

    2012-01-01

    Full Text Available In this study, we investigated whether gongjin-dan improves functional recovery and has neuroprotective effects on reducing the infarct volume after transient middle cerebral artery occlusion (MCAo. Infarct volume was measured using TTC staining and glucose utilization by F-18 FDG PET. Functional improvement was evaluated with the Rota-rod, treadmill, Garcia score test, and adhesive removal test. At 14 days after MCAo, neuronal cell survival, astrocytes expansion, and apoptosis were assessed by immunohistofluorescence staining in the peri-infarct region. Also, the expression of neurotrophic factors and inflammatory cytokines such as VEGF, BDNF, Cox-2, TNF-α, IL-1β, and IL-1α was measured in ischemic hemisphere regions. The gongjin-dan-treated group showed both reduced infarct volume and increased glucose utilization. Behavior tests demonstrated a significant improvement compared to the control. Also in the gongjin-dan treated group, NeuN-positive cells were increased and number of astrocytes, microglia, and apoptotic cells was significantly decreased compared with the control group in the ischemic peri-infarct area. Furthermore, the expression of VEGF and BDNF was increased and level of Cox-2, TNF-α, IL-1β, and IL-1α was decreased. These results suggest that gongjin-dan may improve functional outcome through the rapid restoration of metabolism and can be considered as a potential neuroprotective agent.

  4. Neuroprotective effects of lycopene pretreatment on transient global cerebral ischemia‑reperfusion in rats: The role of the Nrf2/HO‑1 signaling pathway.

    Science.gov (United States)

    Lei, Xiaofeng; Lei, Lijian; Zhang, Zhelin; Cheng, Yan

    2016-01-01

    The present study aimed to investigate the neuroprotective effect of lycopene in a mouse model of bilateral common carotid artery occlusion (BCCAO) and the role of the Nrf2/HO‑1 signaling pathway. A total of 60 male C57BL/6 mice, aged 12 weeks and weighing 20‑24 g, were used in the present study. The mice were randomly assigned to three groups: Control, BCCAO and BCCAO + lycopene. The neurological score was assessed 24, 48 or 72 h following BCCAO. Hematoxylin and eosin staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were performed to detect neuronal death and survival. The production of glutathione (GSH) and reactive oxygen species were detected to investigate the oxidative stress. The expression levels of nuclear factor erythroid 2‑related factor (Nrf2) and Heme oxygenase‑1 (HO‑1) were determined by western blotting. Lycopene significantly improved the neurological score in the BCCAO mice. It attenuated neuronal apoptosis, as indicated by TUNEL staining, and attenuated the oxidative stress induced by global ischemia. Lycopene increased the expression levels of Nrf2 and HO‑1, indicating that the Nrf2/HO‑1 signaling pathway may be involved in the neuroprotective effect of lycopene. The present study revealed that lycopene protects the brain from global ischemic injury, which is associated with its antiapoptotic effect and the activation of the Nrf2/HO‑1 signaling pathway.

  5. Antiepileptic and neuroprotective effects of human umbilical cord blood mononuclear cells in a pilocarpine-induced epilepsy model.

    Science.gov (United States)

    Costa-Ferro, Zaquer Suzana Munhoz; de Borba Cunha, Fernanda; de Freitas Souza, Bruno Solano; Leal, Marcos Maurício Tosta; da Silva, Adelson Alves; de Bellis Kühn, Telma Ingrid Borges; Forte, Andresa; Sekiya, Eliseo Joji; Soares, Milena Botelho Pereira; Dos Santos, Ricardo Ribeiro

    2014-03-01

    Status epilepticus (SE) is a condition of persistent seizure that leads to brain damage and, frequently, to the establishment of chronic epilepsy. Cord blood is an important source of adult stem cells for the treatment of neurological disorders. The present study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (HUCBC) transplanted into rats after induction of SE by the administration of lithium and pilocarpine chloride. Transplantation of HUCBC into epileptic rats protected against neuronal loss in the hippocampal subfields CA1, CA3 and in the hilus of the dentate gyrus, up to 300 days after SE induction. Moreover, transplanted rats had reduced frequency and duration of spontaneous recurrent seizures (SRS) 15, 120 and 300 days after the SE. Our study shows that HUCBC provide prominent antiepileptic and neuroprotective effects in the experimental model of epilepsy and reinforces that early interventions can protect the brain against the establishment of epilepsy.

  6. Novel Neuroprotective Strategies in Ischemic Retinal Lesions

    Science.gov (United States)

    Szabadfi, Krisztina; Mester, Laszlo; Reglodi, Dora; Kiss, Peter; Babai, Norbert; Racz, Boglarka; Kovacs, Krisztina; Szabo, Aliz; Tamas, Andrea; Gabriel, Robert; Atlasz, Tamas

    2010-01-01

    Retinal ischemia can be effectively modeled by permanent bilateral common carotid artery occlusion, which leads to chronic hypoperfusion-induced degeneration in the entire rat retina. The complex pathways leading to retinal cell death offer a complex approach of neuroprotective strategies. In the present review we summarize recent findings with different neuroprotective candidate molecules. We describe the protective effects of intravitreal treatment with: (i) urocortin 2; (ii) a mitochondrial ATP-sensitive K+ channel opener, diazoxide; (iii) a neurotrophic factor, pituitary adenylate cyclase activating polypeptide; and (iv) a novel poly(ADP-ribose) polymerase inhibitor (HO3089). The retinoprotective effects are demonstrated with morphological description and effects on apoptotic pathways using molecular biological techniques. PMID:20386654

  7. Isoflavones prevent bone loss following ovariectomy in young adult rats

    Directory of Open Access Journals (Sweden)

    Chen Li-Ting

    2008-03-01

    Full Text Available Abstract Soy protein, a rich source of phytoestrogens, exhibit estrogen-type bioactivity. The purpose of this study was to determine if ingestion of isoflavones before ovariectomy can prevent bone loss following ovariectomy. Twenty-four nulliparous Wistar rats were randomly divided into four groups. In the normal diet groups, a sham operation was performed on Group A, while ovariectomy was performed on Group B. For Groups C and D, all rats were fed with an isoflavone-rich (25 mg/day diet for one month, then bilateral ovariectomy were performed. In the rats in Group C, a normal diet was begun following the ovariectomy. The rats in Groups D continued to receive the isoflavone-rich diet for two additional months postoperatively. All rats were sacrificed 60 days after surgery. The weight of bone ash of the long bones and whole lumbar spine were determined. A histological study of cancellous bone was done and biochemical indices of skeletal metabolism were performed and analyzed. The markers of bone metabolism exhibited no significant changes. When compared with the sham-operated rats fed a normal diet, the bone mass of ovariectomized rats decreased significantly; pre-ovariectomy ingestion of an isoflavone-rich diet did not prevent bone loss. The bone mass of rats treated with an isoflavone-rich diet for three months was higher than controls two months after ovariectomy. Dietary isoflavones did not prevent the development of post-ovariectomy bone loss, but long-term ingestion of an isoflavone-rich diet increased the bone mineral contents after ovariectomy in young rats.

  8. Morphine treatment during juvenile isolation increases social activity and opioid peptides release in the adult rat.

    Science.gov (United States)

    Van den Berg, C L; Kitchen, I; Gerrits, M A; Spruijt, B M; Van Ree, J M

    1999-05-29

    The consequences of juvenile isolation and morphine treatment on general activity, social activity and endogenous opioid release during a social interaction test were investigated in the adult rat. Rats were either isolated or socially housed during weeks 4 and 5 of age and treated daily during this isolation period subcutaneously with either saline or morphine. Directly after a social interaction test at 10 weeks of age, rats were injected with [3H]-diprenorphine and subsequently prepared for in vivo autoradiography. The autoradiographic technique was used to visualise neuroanatomical changes in opioid receptor occupancy, probably reflecting changes in opioid peptide release, as a result of social activity. Juvenile isolation increased general activity during the social interaction test, an effect which was accompanied by a reduction of opioid receptor occupancy in many brain areas, suggesting an increased opioid peptide release as a consequence of socially-induced general activity. Morphine treatment in isolated rats caused an increase in adult social activity and enhanced opioid peptide release in some cortical regions and the ventral tegmental area as compared to saline treated rats. Both social activity and opioid receptor occupancy were unaffected by morphine treatment in non-isolated rats. The present study underscores the role of opioid systems in adult social behaviors as a consequence of juvenile isolation. The results suggest a relationship between social activity and opioid peptide release during social contact. Increased social activity seems to be accompanied by elevated opioid peptide release in distinct brain areas after morphine treatment during juvenile isolation.

  9. Effect of lindane on antioxidant enzymes in epididymis and epididymal sperm of adult rats

    Institute of Scientific and Technical Information of China (English)

    K.C. Chitra; R. Sujatha; C. Latchoumycandane; P.P. Mathur

    2001-01-01

    Aim: To find out the changes induced by lindane on the antioxidant enzymes in epididymis and epididymal sperm of adult rats, Methods; Adult male rats were orally administered lindane at a dose of 5.0 mg/kg body weight per day for 30 days. At the end of the treatment, the rats were sacrificed. The epididymis was removed and weighed and sperm were collected for sperm count, motility and biochemical studies. A 1% homogenate of epididymis was prepared and used for biochemical estimations. Results: In lindane-treated rats, there were significant reductions in the epididymal weight, epididymal sperm count and motility compared with the controls. Significant decreases in the superoxide dismutase (SOD), catalase, glutathione reductase and glutathione peroxidase activities and significant increases in the H2O2 generation and lipid peroxidation were also observed in the epididymis and epididymal sperm of lindane-treated rats. Conclusion: Lindane decreases the levels of antioxidant enzymes in the epididymis and epididymal sperm of adult rats thereby inducing oxidative stress.

  10. Neuroprotective Effect of Paeonol Mediates Anti-Inflammation via Suppressing Toll-Like Receptor 2 and Toll-Like Receptor 4 Signaling Pathways in Cerebral Ischemia-Reperfusion Injured Rats

    Directory of Open Access Journals (Sweden)

    Wen-Yen Liao

    2016-01-01

    Full Text Available Paeonol is a phenolic compound derived from Paeonia suffruticosa Andrews (MC and P. lactiflora Pall (PL. Paeonol can reduce cerebral infarction volume and improve neurological deficits through antioxidative and anti-inflammatory effects. However, the anti-inflammatory pathway of paeonol remains unclear. This study investigated the relationship between anti-inflammatory responses of paeonol and signaling pathways of TLR2 and TLR4 in cerebral infarct. We established the cerebral ischemia-reperfusion model in Sprague Dawley rats by occluding right middle cerebral artery for 60 min, followed by reperfusion for 24 h. The neurological deficit score was examined, and the brains of the rats were removed for cerebral infarction volume and immunohistochemistry (IHC analysis. The infarction volume and neurological deficits were lower in the paeonol group (pretreatment with paeonol; 20 mg/kg i.p. than in the control group (without paeonol treatment. The IHC analysis revealed that the number of TLR2-, TLR4-, Iba1-, NF-κB- (P50-, and IL-1β-immunoreactive cells and TUNEL-positive cells was significantly lower in the paeonol group; however, the number of TNF-α-immunoreactive cells did not differ between the paeonol and control groups. The paeonol reveals some neuroprotective effects in the model of ischemia, which could be due to the reduction of many proinflammatory receptors/mediators, although the mechanisms are not clear.

  11. Neuroprotective effect of salvianolic acid B against cerebral ischemic injury in rats via the CD40/NF-κB pathway associated with suppression of platelets activation and neuroinflammation.

    Science.gov (United States)

    Xu, Shixin; Zhong, Aiqin; Ma, Huining; Li, Dan; Hu, Yue; Xu, Yingzhi; Zhang, Junping

    2017-04-15

    Neuroinflammation plays a critical role in the pathogenesis of ischemia/reperfusion (I/R) injury. Activated platelets are increasingly regarded as initiators and/or amplifiers of inflammatory processes in cerebral I/R injury. Salvianolic acid B (SAB) is the most abundant bioactive compound of Salviae miltiorrhizae, a well-known Chinese herb used to promote blood circulation and eliminating blood stasis. S. miltiorrhizae has been used clinically in Asia for the treatment of ischemic cerebrovascular diseases. In the present study, a rat model of transient middle cerebral artery occlusion (tMCAO) was established to investigate the neuroprotective effects and mechanisms of SAB treatment against focal cerebral I/R insult. The results showed that SAB treatment (3mg/kg, 6mg/kg and 12mg/kg, i.p.) dose-dependently decreased I/R-induced neurological deficits at 24, 48, and 72h after reperfusion and decreased plasma-soluble P-selectin and soluble CD40 ligand as early as 6h after onset of I/R insult. At 24h after reperfusion, SAB treatment significantly reduced neuronal and DNA damage in the hippocampal CA1 region and decreased neural cell loss in the ischemic core. The I/R-induced pro-inflammatory mediator mRNA and protein overexpression in the penumbra cortex, including ICAM-1, IL-1β, IL-6, IL-8, and MCP-1, were significantly inhibited by SAB in a dose-dependent manner. Further studies suggested SAB treatment attenuated CD40 expression and NF-κB activation, which involved NF-κB/p65 phosphorylation and IκBα phosphorylation and degradation. In conclusion, our findings indicated that the neuroprotective effects of SAB post cerebral I/R injury are associated with the inhibition of both platelets activation and production of pro-inflammatory mediators and the downregulation of the CD40/NF-κB pathway.

  12. Early treatment with metformin induces resistance against tumor growth in adult rats.

    Science.gov (United States)

    Trombini, Amanda B; Franco, Claudinéia Cs; Miranda, Rosiane A; de Oliveira, Júlio C; Barella, Luiz F; Prates, Kelly V; de Souza, Aline A; Pavanello, Audrei; Malta, Ananda; Almeida, Douglas L; Tófolo, Laize P; Rigo, Kesia P; Ribeiro, Tatiane As; Fabricio, Gabriel S; de Sant'Anna, Juliane R; Castro-Prado, Marialba Aa; de Souza, Helenir Medri; de Morais, Hely; Mathias, Paulo Cf

    2015-01-01

    It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells. Adult rats that were treated with metformin during adolescence presented inhibition of tumor growth, and animals that were treated during adult life did not demonstrate any changes in tumor growth. Although we do not have data to disclose a molecular mechanism to the preventive metformin effect, we present, for the first time, results showing that cancer growth in adult life is dependent on early life intervention, thus supporting a new therapeutic prevention for cancer.

  13. [Disruption of latent inhibition in adult rats after prepubertal dopamine terminals lesions in the ventral hippocampus].

    Science.gov (United States)

    Loskutova, L V; Kostiunina, N V; Red'kina, A V

    2010-05-01

    Wistar rats were submitted to bilateral ventral hippocampal injection of 6-hydroxydopamine on 32nd day after birth. Latent inhibition was measured in passive or active avoidance tasks when the rats received 20 and 100 pre-exposures of conditioned stimulus. Prepubertal and adult lesioned rats showed a deficit in the latent inhibition but not in the capacity to avoidance learning in presence of the conditioned stimulus novelty. Possible mechanism of the involvement of hippocampal dopaminergic terminals in attention inhibition to irrelevant information is considered.

  14. Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression

    DEFF Research Database (Denmark)

    Henningsen, Kim; Dyrvig, Mads; Bouzinova, Elena V

    2012-01-01

    In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats...... to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic...... exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant...

  15. HISTOLOGICAL STUDIES OF THE EFFECTS OF RED PEPPER ON THE STOMACH OF ADULT WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Josiah O. Adjene

    2007-01-01

    Full Text Available Histological effects of red pepper commonly used as spice in food on the stomach of adult wistar rats were carefully investigated. The rats of both sexes (n=24, average weight of 200g were randomly assigned into two treatments (n=16 and control (n=6 groups. The rats in the treatments groups received 1g and 2g of red pepper thoroughly mixed with 20g of their feeds for 7 and 14 days, while the control rats received equal amounts of feeds without the red pepper added. The rats were fed with grower's mash purchased from Edo feeds and flour mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day eight and fifteen of the experiment respectively.The stomach was carefully dissected out and quickly fixed in 10% formol saline for routine histological procedure after H & E method.The histological findings after H&E methods indicated that the treated sections of the stomach showed some level of cellular hypertrophy, congestion of blood vessels degenerative changes disruption and distortion of the cytoarchitecture of the stomach.These findings indicate that red pepper may have some deleterious effects on the microanatomy of the stomach of adult wistar rat at higher doses. It is recommended that further studies aimed at corroborating these findings be carried out.

  16. HISTOLOGICAL STUDIES OF THE EFFECTS OF MONOSODIUM GLUTAMATE ON THE INFERIOR COLLICULUS OF ADULT WISTAR RATS.

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    A.O. Eweka.

    2008-01-01

    Full Text Available Histological effects of Monosodium glutamate (MSG commonly used as food additive on the inferior colliculus (IC of adult Wistar rats were carefully studied. The rats of both sexes (n=24, average weight of 185g were randomly assigned into two treatments (n=16 and control (n=8 groups. The rats in the treatment groups received 3g and 6g of MSG thoroughly mixed with their feeds for fourteen days, while the control rats received equal amounts of feeds without MSG added. The rats were fed with growers' mash purchased from Edo Feeds and Flour Mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day fifteen of the experiment. The inferior colliculus was carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H&E method.The histological findings after H&E methods indicated that the treated sections of the inferior colliculus showed some cellular degenerative changes, cellular hypertrophy, and autophagic vacuoles with some intercellular vacuolations appearing in the stroma, and some degree of neuronal hypertrophy when compared to the control sections.These findings indicate that MSG consumption may have a deleterious effect on the neurons of the inferior colliculus (IC. MSG may probably have adverse effects on the auditory sensibilities by its deleterious effects on the nerve cells of the IC of adult Wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out.

  17. Histological effects of chronic consumption of soda pop drinks on kidney of adult Wister rats

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    Josiah Obaghwarhievwo Adjene

    2010-05-01

    Full Text Available Background: Health concerns over soda pop drinks have been severally report. However, histological perspectives are not very common. Aim: The objective of this study is to investigate histological effect of chronic consumption of soda pop drinks on the kidney of adult Wistar rats. Materials and methods: The rats of both sexes (n = 24, with average weight of 200g were randomly assigned into two treatment (A & B (n=16 and Control (c (n=8 groups. The rats in the treatment group (A received a brand of soda pop drink on a daily basis for thirty days. The rats in treatment group (B received another brand of soda drink, while the control group (C received equal amount of water for the same period. The rats were given the drinks as well as feeds liberally for thirty days, and sacrificed by cervical dislocation on the thirty-first day of the experiment. The kidney was carefully dissected out and quickly fixed in 10% formal saline for histological study. Results: The findings indicate that rats in the treated groups (A&B showed some varying degree of distortion and disruption of the renal structure. There are observable diffuse signs of glomerulonephritis with some congestion and tubular necrosis as compared to the control group. Conclusion: Chronic consumption of soda pop drinks may affect the microanatomy of the kidney of adult Wistar rats. Further study aimed at corroborating these observations in humans is warranted.

  18. Histological effects of chronic consumption of soda pop drinks on kidney of adult Wister rats

    Directory of Open Access Journals (Sweden)

    Josiah Obaghwarhievwo Adjene

    2010-01-01

    Full Text Available Background : Health concerns over soda pop drinks have been severally report. However, histological perspectives are not very common. Aim: The objective of this study is to investigate histological effect of chronic consumption of soda pop drinks on the kidney of adult Wistar rats. Materials and methods : The rats of both sexes (n = 24, with average weight of 200g were randomly assigned into two treatment (A & B (n=16 and Control (c (n=8 groups. The rats in the treatment group (A received a brand of soda pop drink on a daily basis for thirty days. The rats in treatment group (B received another brand of soda drink, while the control group (C received equal amount of water for the same period. The rats were given the drinks as well as feeds liberally for thirty days, and sacrificed by cervical dislocation on the thirty-first day of the experiment. The kidney was carefully dissected out and quickly fixed in 10% formal saline for histological study. Results : The findings indicate that rats in the treated groups (A&B showed some varying degree of distortion and disruption of the renal structure. There are observable diffuse signs of glomerulonephritis with some congestion and tubular necrosis as compared to the control group. Conclusion : Chronic consumption of soda pop drinks may affect the microanatomy of the kidney of adult Wistar rats. Further study aimed at corroborating these observations in humans is warranted.

  19. HISTOLOGICAL EFFECTS OF CHRONIC CONSUMPTION OF NUTMEG ON THE LATERAL GENICULATE BODY OF ADULT WISTAR RATS.

    Directory of Open Access Journals (Sweden)

    J.O. Adjene

    2010-01-01

    Full Text Available The effects of chronic consumption of nutmeg commonly used as a spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the lateral geniculate body of adult wistar rats was studied.The rats of both sexes, with average weight of 200g were randomly assigned into treatment and control groups. The rats in the treatment group (n=8 received 2g of nutmeg thoroughly mixed with the feeds on a daily basis for thirty-two days. The control group (n=8 received equal amount of feeds daily without nutmeg added for thirty-two days. The growers mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo State, Nigeria and the rats were given water liberally. The rats were sacrificed on the thirty-three day of the experiment. The lateral geniculate body was carefully dissected out and quickly fixed in 10% formal saline for histological study.The findings indicate that rats in the treated group showed some cellular degenerative changes like sparse cellular population, pyknotic nuclei with some microcystic changes, edema and vacuolations in the stroma of the treated lateral geniculate body as compared to that of the control group.Chronic consumption of nutmeg may therefore have an adverse effect on the visual sensibilities by affecting the microanatomy of the lateral geniculate body of adult wistar rats. It is recommended for further studies aimed at corroborating these observations.

  20. Neonatal sensory deprivation promotes development of absence seizures in adult rats with genetic predisposition to epilepsy.

    Science.gov (United States)

    Sitnikova, Evgenia

    2011-03-04

    Absence epilepsy has age-related onset. In a WAG/Rij rat genetic model, absence seizures appear after puberty and they are increased with age. It is known that (1) epileptic activity in WAG/Rij rats is initiated at the perioral area in the somatosensory cortex; (2) sensory deprivation, i.e., whisker trimming during the critical period of development, could enhance excitatory activity in the somatosensory cortex. It is hypothesized that the cortex may become more excitable after neonatal vibrissae removal, and this may precipitate absence seizures in adult rats. We found that whisker trimming during the first postnatal weeks caused more rapid development of EEG seizure activity in adult WAG/Rij rats. Epileptic discharges in the trimmed rats were more numerous (vs control), showed longer duration and often appeared in desynchronized and drowsy EEG. The number of absence-like spindle-shaped EEG events (spike-wave spindles) in the whisker-trimmed rats was higher than in control, especially during the intermediate sleep state. An age-dependent increase of intermediate sleep state was found in the trimmed rats, but not in the intact animals. We discuss epigenetic factors that can modulate absence epilepsy in genetically prone subjects.

  1. Influence of superior cervical ganglionectomy on hippocampal neurogenesis and learning and memory in adult rats

    Institute of Scientific and Technical Information of China (English)

    Yanping Ding; Baoping Shao; Shiyuan Yu; Shanting Zhao; Jianlin Wang

    2009-01-01

    BACKGROUND: Studies have shown that neurogenesis in the dentate gyrus plays an important role in learning and memory. However, studies have not determined whether the superior cervical ganglion or the sympathetic nerve system influences hippocampal neurogenesis or learning and memory in adult rats. OBJECTIVE: To observe differences in dentate gyrus neurogenesis, as well as learning and memory, in adult rats following superior cervical ganglionectomy. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Immunohistochemistry Laboratory of the School of Life Sciences in Lanzhou University from July 2006 to July 2007.MATERIALS: Doublecortin polyclonal antibody was provided by Santa Cruz Biotechnology, USA;avidin-biotin-peroxidase complex was purchased from Zhongshan Goldenbride Biotechnology, China;Morris water maze was bought from Taimeng Technology, China. METHODS: A total of 20 adult, male, Wistar rats were randomly divided into surgery and control groups, with 10 rats in each group. In the surgery group, the bilateral superior cervical ganglions were transected. In the control group, the superior cervical ganglions were only exposed, but no ganglionectomy was performed. MAIN OUTCOME MEASURES: To examine distribution, morphology, and number of newborn neurons in the dentate gyrus using doublecortin immunohistochemistry at 36 days following surgical procedures. To examine ability of learning and memory in adult rats using the Morris water maze at 30 days following surgical procedures. RESULTS: Doublecortin immunohistochemical results showed that a reduction in the number of doublecortin-positive neurons in the surgery group compared to the control group (P<0.05), while the distribution of doublecortin-positive neurons was identical in the two groups. The surgery group exhibited significantly worse performance in learning and spatial memory tasks compared to the control group (P<0.05). CONCLUSION: Superior cervical ganglionectomy

  2. Neuroprotection by JM-20 against oxygen-glucose deprivation in rat hippocampal slices: Involvement of the Akt/GSK-3β pathway.

    Science.gov (United States)

    Ramírez-Sánchez, Jeney; Simões Pires, Elisa Nicoloso; Nuñez-Figueredo, Yanier; Pardo-Andreu, Gilberto L; Fonseca-Fonseca, Luis Arturo; Ruiz-Reyes, Alberto; Ochoa-Rodríguez, Estael; Verdecia-Reyes, Yamila; Delgado-Hernández, René; Souza, Diogo O; Salbego, Christianne

    2015-11-01

    Cerebral ischemia is the third most common cause of death and a major cause of disability worldwide. Beyond a shortage of essential metabolites, ischemia triggers many interconnected pathophysiological events, including excitotoxicity, oxidative stress, inflammation and apoptosis. Here, we investigated the neuroprotective mechanisms of JM-20, a novel synthetic molecule, focusing on the phosphoinositide-3-kinase (PI3K)/Akt survival pathway and glial cell response as potential targets of JM-20. For this purpose, we used organotypic hippocampal slice cultures exposed to oxygen-glucose deprivation (OGD) to achieve ischemic/reperfusion damage in vitro. Treatment with JM-20 at 0.1 and 10 μM reduced PI incorporation (indicative of cell death) after OGD. OGD decreased the phosphorylation of Akt (pro-survival) and GSK 3β (pro-apoptotic), resulting in respective inhibition and activation of these proteins. Treatment with JM20 prevented the reduced phosphorylation of these proteins after OGD, representing a shift from pro-apoptotic to pro-survival signaling. The OGD-induced activation of caspase-3 was also attenuated by JM-20 treatment at 10 μM. Moreover, in cultures treated with JM-20 and exposed to OGD conditioning, we observed a decrease in activated microglia, as well as a decrease in interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α release into the culture medium, while the level of the anti-inflammatory IL-10 increased. GFAP immunostaining and IB4 labeling showed that JM-20 treatment significantly augmented GFAP immunoreactivity after OGD, when compared with cultures exposed to OGD only, suggesting the activation of astroglial cells. Our results confirm that JM-20 has a strong neuroprotective effect against ischemic injury and suggest that the mechanisms involved in this effect may include the modulation of reactive astrogliosis, as well as neuroinflammation and the anti-apoptotic cell signaling pathway.

  3. 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.

  4. Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

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    Lu Kong

    2014-11-01

    Full Text Available Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH and luteinizing hormone (LH, and lowered etradiol (E2 serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions.

  5. EFFECTS OF CEREBRAL CORTICAL CONCIS ON CELL PROLIFERATION OF THE SUBVENTRICULAR ZONE IN ADULT RATS

    Institute of Scientific and Technical Information of China (English)

    Zhang Yuelin; Qiu Shudong; Zhang Pengbo; Shi Wei

    2006-01-01

    Objective To investigate the proliferative response and time course of endogenous neural stem/progenitor cells after cerebral cortical concis in the adult rats. Methods Eighty adult male Sprague-Dawley rats were used in this study. Cumulative BrdU labeling was employed to detect the proliferating cells. At 1 d, 3 d, 7 d, 14 d, and 21 d after cerebral cortical concis, the rats were killed for BrdU immunohistochemical staining and cell counting in the injured ipsilateral SVZ. Results Little BrdU immunoreactivity cells was present in SVZ of the control rats from day 7 to day 21 after sham operation. The number of BrdU immunoreactivity cells in the injured ipsilateral SVZ increased at day 1 and peaked at day 7 after cerebral cortical concis. Conclusion After cerebral cortical concis of the adult rats, neural stem/progenitor cells in the injured ipsilateral SVZ markedly proliferated with a peak at day 7. This finding may be important for manipulating SVZ cells to promote the recovery from cerebral cortical concis.

  6. Cocaine self-administration punished by intravenous histamine in adolescent and adult rats.

    Science.gov (United States)

    Holtz, Nathan A; Carroll, Marilyn E

    2015-06-01

    Adolescence is a transitional phase marked by a heightened vulnerability to substances of abuse. It has been hypothesized that both increased sensitivity to reward and decreased sensitivity to aversive events may drive drug-use liability during this phase. To investigate possible age-related differences in sensitivity to the aversive consequences of drug use, adolescent and adult rats were compared on self-administration of cocaine before, during, and after a 10-day period in which an aversive agent, histamine, was added to the cocaine solution. Adult and adolescent female rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4 mg/kg/infusion) was then added directly into the cocaine solution for the next 10 sessions. Finally, the cocaine/histamine solution was replaced with a cocaine-only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20 sessions. Compared with adolescent rats, adult rats showed a greater decrease in cocaine self-administration when it was punished with intravenous histamine compared with their baseline cocaine self-administration rates. These results suggest that differences in the sensitivity to negative consequences of drug use may partially explain developmental differences in drug use vulnerability.

  7. Effect of lindane on testicular antioxidant system and steroidogenic enzymes in adult rats

    Institute of Scientific and Technical Information of China (English)

    R. Sujatha; K.C. Chitin; C. Latchoumycandane; P.P. Mathur

    2001-01-01

    Aim: To find out the effect of lindane on testicular antioxidant system and testicular steroidogenesis in adult male rats. Methods: Adult male rats were orally administered with lindane at a dose of 5.0 mg/kg body weight per day for 30 days. Twenty-four hours after the last treatment the rats were killed using anesthetic ether. Testes, epididymis,seminal vesicles and ventral prostate were removed and weighed. A 10% testicular homogenate was prepared and cen trifuged at 4°C. The supematant was used for various biochemical estimations. Results: The body weight and the weights of testes, epididymis, seminal vesicles and ventral prostate were reduced in lindane-treated rars. There was asignificant decline in the activities of antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione reduc tase while an increase in hydrogen peroxide (H2O2) generation was observed. The specific activities of testicular steroidogenic enzymes 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were decreased. The levels of DNA, RNA and protein were also decreased in lindane-treated rats. Conclusion: Lindane induces oxida tive stress and decreases antioxidant enzymes in adult male rats.

  8. Prenatal Choline Availability Alters the Context Sensitivity of Pavlovian Conditioning in Adult Rats

    Science.gov (United States)

    Lamoureux, Jeffrey A.; Meck, Warren H.; Williams, Christina L.

    2008-01-01

    The effects of prenatal choline availability on Pavlovian conditioning were assessed in adult male rats (3-4 mo). Neither supplementation nor deprivation of prenatal choline affected the acquisition and extinction of simple Pavlovian conditioned excitation, or the acquisition and retardation of conditioned inhibition. However, prenatal choline…

  9. Positron emission tomography for serial imaging of the contused adult rat spinal cord.

    NARCIS (Netherlands)

    Nandoe, R.D.S.; Yu, J.; Seidel, J.; Rahiem, S.T.; Hurtado, A.; Tsui, B.M.; Grotenhuis, J.A.; Pomper, M.G.; Oudega, M.

    2010-01-01

    We investigated whether small-animal positron emission tomography (PET) could be used in combination with computed tomography (CT) imaging techniques for longitudinal monitoring of the injured spinal cord. In adult female Sprague-Dawley rats (n = 6), the ninth thoracic (T9) spinal cord segment was e

  10. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

    Science.gov (United States)

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

  11. The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

    Science.gov (United States)

    Fialová, Markéta; Šírová, Jana; Bubeníková-Valešová, Věra; Šlamberová, Romana

    2015-01-01

    The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

  12. Monitoring of intermittent PTH(1-34) treatment by serum PINP in adult ovariectomized osteopenic rats

    DEFF Research Database (Denmark)

    Halleen, Jussi; Peng, ZhiQi; Fagerlund, Katja

    , allowing measurement of serum PINP in preclinical rodent osteoporosis models. The purpose of this study was to evaluate the use of serum PINP for monitoring intermittent PTH(1-34) treatment in adult ovariectomized (OVX) osteopenic rats. Study groups included a sham-operated control group and an OVX...

  13. Reinnervation of muscles after transection of the sciatic nerve in adult rats

    NARCIS (Netherlands)

    Ijkema-Paassen, J; Meek, MF; Gramsbergen, A

    2002-01-01

    Functional recovery after transection of the sciatic nerve in adult rats is poor, probably because of abnormalities in reinnervation. Denervation and reinnervation patterns were studied morphologically in the lateral gastrocnemius (LGC), tibialis anterior (TA), and soleus (SOL) muscles for 21 weeks

  14. Peripheral effect of NMDA receptor antagonists on adult rats exposed to neonatal colon pain

    Institute of Scientific and Technical Information of China (English)

    ChunLin; ElieD.Al-Chaer

    2004-01-01

    AIM: Previous work done by Al-Chaer' s lab has shown that colon irritation (CI) in neonates can lead to chronic visceral hypersensitivity in adult rats, with characteristics of visceral allodynia and hyperalgesia, associated with central neuronal sensitization in the absence of identifiable peripheral pathology (Al-Chaer et al. 2000) . The pathogenesis of

  15. Strain differences in baroceptor reflex in adult Wistar Kyoto rats

    Directory of Open Access Journals (Sweden)

    Vitor E. Valenti

    2010-01-01

    Full Text Available OBJECTIVES: A subset of normotensive Sprague-Dawley rats show lower baroreflex sensitivity; however, no previous study investigated whether there are differences in baroreflex sensitivity within this subset. Our study compared baroreflex sensitivity among conscious rats of this specific subtype. METHODS: Male Wistar Kyoto (WKY rats (16 weeks old were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure (MAP and heart rate (HR. Baroreflex gain was calculated as the ratio between change in HR and MAP variation (ΔHR/ΔMAP in response to a depressor dose of sodium nitroprusside (SNP, 50 µg/kg, i.v. and a pressor dose of phenylephrine (PE, 8 µg/kg, i.v.. Rats were divided into four groups: 1 low bradycardic baroreflex (LB, baroreflex gain (BG between -1 and -2 bpm/mmHg tested with PE; 2 high bradycardic baroreflex (HB, BG < -2 bpm/mmHg tested with PE; 3 low tachycardic baroreflex (LT, BG between -1 and -2 bpm/mmHg tested with SNP and; 4 high tachycardic baroreflex (HT, BG < -2 bpm/mmHg tested with SNP. Significant differences were considered for p < 0.05. RESULTS: Approximately 37% of the rats showed a reduced bradycardic peak, bradycardic reflex and decreased bradycardic gain of baroreflex while roughly 23% had a decreased basal HR, tachycardic peak, tachycardic reflex and reduced sympathetic baroreflex gain. No significant alterations were noted with regard to basal MAP. CONCLUSION: There is variability regarding baroreflex sensitivity among WKY rats from the same laboratory.

  16. Increased expression of neurotrophin 4 following focal cerebral ischemia in adult rat brain with treadmill exercise.

    Directory of Open Access Journals (Sweden)

    Jin-Young Chung

    Full Text Available Neurotrophin 4 (NT-4 belongs to the family of neurotrophic factors, and it interacts with the tyrosine kinase B (trkB receptor. NT-4 has neuroprotective effects following cerebral ischemia. Its role might be similar to brain-derived neurotrophic factor (BDNF, because both interact with trkB. Exercise also improves neural function by increasing neurotrophic factors. However, expression profiles of NT-4 in the brain during exercise are unknown. Here, we assessed the expressions of NT-4 and its receptor, trkB, following cerebral ischemia and hypothesized that exercise changes the expressions of NT-4 and trkB. Results showed that in a permanent middle cerebral artery occlusion rat model, ischemia decreased NT-4 and trkB expression. Immunohistochemistry showed their immunoreactivities around the region of the ischemic area. Treadmill exercise changed the expression of NT-4, which increased in the contralateral hemisphere in rats with ischemic injury. TrkB also showed similar patterns to its neurotophins. The change in NT-4 suggested that exercise might have primed NT4 production so that further injury causes slightly greater increases in NT4 compared with non-exercise controls.

  17. Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

    Science.gov (United States)

    Oosthuizen, M K; Amrein, I

    2016-06-02

    Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species.

  18. Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour.

    Science.gov (United States)

    Newson, Penny N; van den Buuse, Maarten; Martin, Sally; Lynch-Frame, Ann; Chahl, Loris A

    2014-10-01

    Treatment of neonatal rats with the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, produces life-long loss of sensory neurons expressing TRPV1 channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioural hyperactivity in a novel environment at 5-7 weeks of age and brain changes reminiscent of those found in subjects with schizophrenia. The objective of the present study was to investigate brain and behavioural responses of adult rats treated as neonates with capsaicin. It was found that the brain changes found at 5-7 weeks in rats treated as neonates with capsaicin persisted into adulthood (12 weeks) but were less in older rats (16-18 weeks). Increased prepulse inhibition (PPI) of acoustic startle was found in these rats at 8 and 12 weeks of age rather than the deficit commonly found in animal models of schizophrenia. Subjects with schizophrenia also have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role of TRPV1 channels in schizophrenia is worthy of investigation.

  19. The role of apelin in the modulation of gastric and pancreatic enzymes activity in adult rats.

    Science.gov (United States)

    Antuschevich, H; Kapica, M; Krawczynska, A; Herman, A; Kato, I; Kuwahara, A; Zabielski, R

    2016-06-01

    Apelin is considered as important gut regulatory peptide ligand of APJ receptor with a potential physiological role in gastrointestinal cytoprotection, regulation of food intake and drinking behavior. Circulating apelin inhibits secretion of pancreatic juice through vagal- cholecystokinin-dependent mechanism and reduces local blood flow. Our study was aimed to determine the effect of fundectomy and intraperitoneal or intragastric administration of apelin-13 on pancreatic and gastric enzymes activities in adult rats. Fundectomy is a surgical removal of stomach fundus - maine site apelin synthesis. Three independent experiments were carried out on Wistar rats. In the first and second experiment apelin-13 was given by intragastric or intraperitoneal way twice a day for 10 days (100 nmol/kg b.w.). Control groups received the physiological saline respectively. In the third experiment the group of rats after fundectomy were used. Fundectomized rats did not receive apelin and the rats from control group were 'sham operated'. At the end of experiment rats were sacrificed and blood from rats was withdrawn for apelin and CCK (cholecystokinin) radioimmunoassay analysis and pancreas and stomach tissues were collected for enzyme activity analyses. Intragastric and intraperitoneal administrations of apelin-13 increased basal plasma CCK level and stimulated gastric and pancreatic enzymes activity in rats. In animals after fundectomy decreased activity of studied enzymes was observed, as well as basal plasma apelin and CCK levels. In conclusion, apelin can effects on CCK release and stimulates some gastric and pancreatic enzymes activity in adult rats while fudectomy suppresses those processes. Changes in the level of pancreatic lipase activity point out that apelin may occurs as a regulator of lipase secretion.

  20. Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Nabi Shamsaei; Mehdi Khaksari; Sohaila Erfani; Hamid Rajabi; Nahid Aboutaleb

    2015-01-01

    Recent evidence has suggested the neuroprotective effects of physical exercise on cerebral isch-emic injury. However, the role of physical exercise in cerebral ischemia-induced hippocampal damage remains controversial. The aim of the present study was to evaluate the effects of pre-ischemia treadmill training on hippocampal CA1 neuronal damage after cerebral ischemia. Male adult rats were randomly divided into control, ischemia and exercise + ischemia groups. In the exercise + ischemia group, rats were subjected to running on a treadmill in a designated time schedule (5 days per week for 4 weeks). Then rats underwent cerebral ischemia induction th rough occlusion of common carotids followed by reperfusion. At 4 days after cerebral ischemia, rat learning and memory abilities were evaluated using passive avoidance memory test and rat hippocampal neuronal damage was detected using Nissl and TUNEL staining. Pre-ischemic ex-ercise signiifcantly reduced the number of TUNEL-positive cells and necrotic cell death in the hippocampal CA1 region as compared to the ischemia group. Moreover, pre-ischemic exercise significantly prevented ischemia-induced memory dysfunction. Pre-ischemic exercise mighct prevent memory deficits after cerebral ischemia through rescuing hippocampal CA1 neurons from ischemia-induced degeneration.

  1. Body and Testicular Weight Changes in Adult Wistar Rats Following Oral Administration of Artesunate

    Directory of Open Access Journals (Sweden)

    al-hassan m. izunya

    2010-05-01

    Full Text Available This experiment was designed to study the effects on the body and testicular weights of adult wistar rats that recieved an oral administration of normal and double normal doses of artesunate. The rats were divided into three groups (A, B and C of five rats each. A and B served as the treatment groups, while C served as the control group. Group A rats were given 4mg.kg-1 b.w of artesunate daily for 3 days followed by 2mg.kg-1 b.w daily for next for 4 days. Group B rats were given 8mg.kg-1 b.w of artesunate daily for 3 days followed by 4mg.kg-1 b.w daily for next 4 days, while group C rats were given only distilled water. The rats were fed with grower's mash purchased from Edo feeds and Flour Mill Ltd, Ewu, Edo state and were given w ater ad libitum. On day eight of the experiment, the rats were weighed and sacrificed. The testes w ere carefully dissected out, freed from adherent tissues and weighed to the nearest 0.001 g. The results showed no changes in body weight of rats in groups A, B and C. There was also no significant change in testicular weight of rats in group A. However a significant increase in testicular weight was observed in group C. Our results suggest that artesunate at normal and double normal doses, has no effect on body weight of rats but may be toxic to the testes at higher doses. It is uncertain however if these changes are reversible. It is recommended therefore, that further studies aimed at corroborating these observations be carried out.

  2. Desvenlafaxine may accelerate neuronal maturation in the dentate gyri of adult male rats.

    Directory of Open Access Journals (Sweden)

    Aditya Asokan

    Full Text Available Adult hippocampal neurogenesis has been linked to the effects of anti-depressant drugs on behavior in rodent models of depression. To explore this link further, we tested whether the serotonin-norepinephrine reuptake inhibitor (SNRI venlafaxine impacted adult hippocampal neurogenesis differently than its primary active SNRI metabolite desvenlafaxine. Adult male Long Evans rats (n = 5-6 per group were fed vehicle, venlafaxine (0.5 or 5 mg or desvenlafaxine (0.5 or 5 mg twice daily for 16 days. Beginning the third day of drug treatment, the rats were given a daily bromodeoxyuridine (BrdU; 50 mg/kg injection for 5 days to label dividing cells and then perfused 2 weeks after the first BrdU injection to confirm total new hippocampal cell numbers and their phenotypes. The high desvenlafaxine dose increased total new BrdU+ cell number and appeared to accelerate neuronal maturation because fewer BrdU+ cells expressed maturing neuronal phenotypes and more expressed mature neuronal phenotypes in the dentate gyri of these versus vehicle-treated rats. While net neurogenesis was not increased in the dentate gyri of rats treated with the high desvenlafaxine dose, significantly more mature neurons were detected. Our data expand the body of literature showing that antidepressants impact adult neurogenesis by stimulating NPC proliferation and perhaps the survival of neuronal progeny and by showing that a high dose of the SNRI antidepressant desvenlafaxine, but neither a high nor low venlafaxine dose, may also accelerate neuronal maturation in the adult rat hippocampus. These data support the hypothesis that hippocampal neurogenesis may indeed serve as a biomarker of depression and the effects of antidepressant treatment, and may be informative for developing novel fast-acting antidepressant strategies.

  3. Dermal penetration of [14C]captan in young and adult rats.

    Science.gov (United States)

    Fisher, H L; Hall, L L; Sumler, M R; Shah, P V

    1992-07-01

    Age dependence in dermal absorption has been a major concern in risk assessment. Captan, a chloroalkyl thio heterocyclic fungicide, was selected for study of age dependence as representative of this class of pesticides. Dermal penetration of [14C]captan applied at 0.286 mumol/cm2 was determined in young (33-d-old) and adult (82-d-old) female Fischer 344 rats in vivo and by two in vitro methods. Dermal penetration in vivo at 72 h was about 9% of the recovered dose in both young and adult rats. The percentage penetration was found to increase as dosage (0.1, 0.5, 2.7 mumol/cm2) decreased. Two in vitro methods gave variable dermal penetration values compared with in vivo results. A static system yielded twofold higher dermal penetration values compared with in vivo results for both young and adult rats. A flow system yielded higher dermal penetration values in young rats and lower penetration values in adults compared with in vivo results. Concentration in body, kidney, and liver was less in young than in adult rats given the same absorbed dosage. A physiological pharmacokinetic model was developed having a dual compartment for the treated skin and appeared to describe dermal absorption and disposition well. From this model, tissue/blood ratios of captan-derived radioactivity for organs were found to range from 0.35 to 3.4, indicating no large uptake or binding preferences by any organ. This preliminary pharmacokinetic model summarizes the experimental findings and could provide impetus for more complex and realistic models.

  4. Effect of prenatal programming and postnatal rearing on glomerular filtration rate in adult rats.

    Science.gov (United States)

    Lozano, German; Elmaghrabi, Ayah; Salley, Jordan; Siddique, Khurrum; Gattineni, Jyothsna; Baum, Michel

    2015-03-01

    The present study examined whether a prenatal low-protein diet programs a decrease in glomerular filtration rate (GFR) and an increase in systolic blood pressure (BP). In addition, we examined whether altering the postnatal nutritional environment of nursing neonatal rats affected GFR and BP when rats were studied as adults. Pregnant rats were fed a normal (20%) protein diet or a low-protein diet (6%) during the last half of pregnancy until birth, when rats were fed a 20% protein diet. Mature adult rats from the prenatal low-protein group had systolic hypertension and a GFR of 0.38 ± 0.03 versus 0.57 ± 0.05 ml·min(-1)·100 g body wt(-1) in the 20% group (P < 0.01). In cross-fostering experiments, mothers continued on the same prenatal diet until weaning. Prenatal 6% protein rats cross-fostered to a 20% mother on day 1 of life had a GFR of 0.53 ± 0.05 ml·min(-1)·100 g body wt(-1), which was not different than the 20% group cross-fostered to a different 20% mother (0.45 ± 0.04 ml·min(-1)·100 g body wt(-1)). BP in the 6% to 20% group was comparable with the 20% to 20% group. Offspring of rats fed either 20% or 6% protein diets during pregnancy and cross-fostered to a 6% mother had elevated BP but a comparable GFR normalized to body weight as the 20% to 20% control group. Thus, a prenatal low-protein diet causes hypertension and a reduction in GFR in mature adult offspring, which can be modified by postnatal rearing.

  5. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

    Energy Technology Data Exchange (ETDEWEB)

    Zago, A. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Leão, R.M.; Carneiro-de-Oliveira, P.E. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil); Marin, M.T.; Cruz, F.C. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Planeta, C.S. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil)

    2011-11-18

    Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

  6. Sativex-like combination of phytocannabinoids is neuroprotective in malonate-lesioned rats, an inflammatory model of Huntington's disease: role of CB1 and CB2 receptors.

    Science.gov (United States)

    Valdeolivas, Sara; Satta, Valentina; Pertwee, Roger G; Fernández-Ruiz, Javier; Sagredo, Onintza

    2012-05-16

    We have investigated whether a 1:1 combination of botanical extracts enriched in either Δ(9)-tetrahydrocannabinol (Δ(9)-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, is neuroprotective in Huntington's disease (HD), using an experimental model of this disease generated by unilateral lesions of the striatum with the mitochondrial complex II inhibitor malonate. This toxin damages striatal neurons by mechanisms that primarily involve apoptosis and microglial activation. We monitored the extent of this damage and the possible preservation of the striatal parenchyma by treatment with a Sativex-like combination of phytocannabinoids using different histological and biochemical markers. Results were as follows: (i) malonate increased the volume of edema measured by in vivo NMR imaging and the Sativex-like combination of phytocannabinoids partially reduced this increase; (ii) malonate reduced the number of Nissl-stained cells, while enhancing the number of degenerating cells stained with FluoroJade-B, and the Sativex-like combination of phytocannabinoids reversed both effects; (iii) malonate caused a strong glial activation (i.e., reactive microglia labeled with Iba-1, and astrogliosis labeled with GFAP) and the Sativex-like combination of phytocannabinoids attenuated both responses; and (iv) malonate increased the expression of inducible nitric oxide synthase and the neurotrophin IGF-1, and both responses were attenuated after the treatment with the Sativex-like combination of phytocannabinoids. We also wanted to establish whether targets within the endocannabinoid system (i.e., CB(1) and CB(2) receptors) are involved in the beneficial effects induced in this model by the Sativex-like combination of phytocannabinoids. This we did using selective antagonists for both receptor types (i.e., SR141716 and AM630) combined with the Sativex-like phytocannabinoid combination. Our results indicated that the effects of this

  7. WIN55,212-2 protects oligodendrocyte precursor cells in stroke penumbra following permanent focal cerebral ischemia in rats

    OpenAIRE

    SUN, JING; Fang, Yin-quan; Ren, Hong; Tao CHEN; Guo, Jing-Jing; Yan, Jun; SONG, SHU; Zhang, Lu-yong; Liao, Hong

    2012-01-01

    Aim: To explore whether the synthetic cannabinoid receptor agonist WIN55,212-2 could protect oligodendrocyte precursor cells (OPCs) in stroke penumbra, thereby providing neuroprotection following permanent focal cerebral ischemia in rats. Methods: Adult male SD rats were subjected to permanent middle cerebral artery occlusion (p-MCAO). The animals were administered WIN55,212-2 at 2 h, and sacrificed at 24 h after the ischemic insult. The infarct volumes and brain swelling were assessed. The e...

  8. Mechanism of Forelimb Motor Function Restoration after Cervical Spinal Cord Hemisection in Rats: A Comparison of Juveniles and Adults

    Directory of Open Access Journals (Sweden)

    Atsushi Hasegawa

    2016-01-01

    Full Text Available The aim of this study was to investigate forelimb motor function after cervical spinal cord injury in juvenile and adult rats. Both rats received a left segmental hemisection of the spinal cord after C3-C4 laminectomy. Behavioral evaluation of motor function was monitored and assessed using the New Rating Scale (NRS and Forelimb Locomotor Scale (FLS and by measuring the range of motion (ROM of both the elbow and wrist. Complete left forelimb motor paralysis was observed in both rats. The NRS showed motor function recovery restored to 50.2±24.7% in juvenile rats and 34.0±19.8% in adult rats. FLS was 60.4±26.8% in juvenile rats and 46.5±26.9% in adult rats. ROM of the elbow and wrist were 88.9±20.6% and 44.4±24.1% in juvenile rats and 70.0±29.2% and 40.0±21.1% in adult rats. Thus, the NRS and ROM of the elbow showed a significant difference between age groups. These results indicate that left hemisection of the cervical spinal cord was not related to right-sided motor functions. Moreover, while motor paralysis of the left forelimb gradually recovered in both groups, the improvement was greater in juvenile rats.

  9. Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat.

    Science.gov (United States)

    Augestad, Ingrid Lovise; Nyman, Axel Karl Gottfrid; Costa, Alex Ignatius; Barnett, Susan Carol; Sandvig, Axel; Håberg, Asta Kristine; Sandvig, Ioanna

    2017-01-24

    Effective transplant-mediated repair of ischemic brain lesions entails extensive tissue remodeling, especially in the ischemic core. Neural stem cells (NSCs) are promising reparative candidates for stroke induced lesions, however, their survival and integration with the host-tissue post-transplantation is poor. In this study, we address this challenge by testing whether co-grafting of NSCs with olfactory ensheathing cells (OECs), a special type of glia with proven neuroprotective, immunomodulatory, and angiogenic effects, can promote graft survival and host tissue remodelling. Transient focal cerebral ischemia was induced in adult rats by a 60-min middle cerebral artery occlusion (MCAo) followed by reperfusion. Ischemic lesions were verified by neurological testing and magnetic resonance imaging. Transplantation into the globus pallidus of NSCs alone or in combination with OECs was performed at two weeks post-MCAo, followed by histological analyses at three weeks post-transplantation. We found evidence of extensive vascular remodelling in the ischemic core as well as evidence of NSC motility away from the graft and into the infarct border in severely lesioned animals co-grafted with OECs. These findings support a possible role of OECs as part of an in situ tissue engineering paradigm for transplant mediated repair of ischemic brain lesions.

  10. HIF‑1 signaling pathway involving iNOS, COX‑2 and caspase‑9 mediates the neuroprotection provided by erythropoietin in the retina of chronic ocular hypertension rats.

    Science.gov (United States)

    Gui, Dongmei; Li, Yanfeng; Chen, Xiaolong; Gao, Dianwen; Yang, Yang; Li, Xun

    2015-02-01

    This study aimed to investigate the impacts of erythropoietin (EPO) on the electroretinogram b‑wave (ERG‑b), and on the mRNA and protein expression levels of hypoxia‑inducible factor‑1α (HIF‑1α), inducible nitric oxide synthase (iNOS), cyclooxygenase‑2 (COX‑2) and caspase‑9 in chronic ocular hypertension rats. Episcleral vein cauterization (EVC) was used to establish the chronic ocular hypertension rat model based on the intraocular pressure (IOP) value. ERG‑b and mRNA and protein expression levels of HIF‑1α, iNOS, COX‑2 and caspase‑9 in normal, EVC‑treated and EVC combined with EPO (EVC+EPO)‑treated rats were measured by electroretinography, RT‑PCR and western blotting, respectively. Moreover, the correlations of HIF‑1α with IOP, ERG‑b, iNOS, COX‑2 and caspase‑9 were evaluated. The mRNA and protein expression levels of HIF‑1α, iNOS, COX‑2 and caspase‑9 in EVC‑treated rats were increased significantly compared with normal rats. The peak expression levels of HIF‑1α, iNOS, COX‑2 and caspase‑9 were respectively obtained 7, 7, 7 and 14 days postoperatively. Compared with EVC‑treated rats, EPO administration weakened the mRNA and protein expression levels of HIF‑1α, iNOS, COX‑2 and caspase‑9. The mRNA expression level of HIF‑1α demonstrated a significant positive correlation with IOP and ERG‑b. HIF‑1α was positively correlated with iNOS, COX‑2 and caspase‑9 at the mRNA and protein levels. The protective effect of EPO on the retina of chronic ocular hypertension rats may be mediated by the HIF‑1 signaling pathway involving iNOS, COX‑2 and caspase‑9.

  11. Neuroprotection from complement-mediated inflammatory damage.

    Science.gov (United States)

    Kulkarni, Amod P; Kellaway, Laurie A; Lahiri, Debomoy K; Kotwal, Girish J

    2004-12-01

    Several neurodegenerative disorders, such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease, are associated with inflammatory damage. The complex process of neuroinflammation involves various components of the immune system and the central nervous system. Particularly, brain astrocytes and microglial cells generate several inflammatory mediators like cytokines, leukotrienes, superoxide radicals, eicasonoids, and the components of the complement cascade. Complement plays an important role in the etiology of most of the neuroinflammatory disorders. To prevent long-term dysfunction inflammation in the central nervous system must be modulated with neuroprotective agents such as nonsteroidal anti-inflammatory drugs, steroids, phenolic thiazoles, nitrones, catechins, nitric oxide synthetase inhibitors, flavonoids, and phosphodiesterase inhibitors. Few drugs are found to be effective and their therapeutic benefit is hampered by side effects. Most of the neuroprotective agents are free radical scavengers and many inhibit only one or two aspects of inflammation. The complement inhibitory activity of most of these agents is either unknown or not established. Thus, there is doubt regarding their therapeutic value in most of the inflammatory disorders in which complement plays a major role. In this context the role of a multifunctional protein, vaccinia virus complement control protein (VCP), is quite significant as it may play a pivotal role in the treatment of several neuroinflammatory disorders. VCP is known to inhibit both complement pathways involved in inflammation. It is also known to inhibit cytokines and chemokines in inflammation. Our recent studies on rats demonstrate that VCP administration inhibits macrophage infiltration, reduces spinal cord destruction, and improves motor skills associated with spinal cord injury, establishing VCP as a strong candidate for neuroprotection. Thus, complement inhibitors such as VCP can serve as neuroprotective

  12. Monosodium Glutamate Dietary Consumption Decreases Pancreatic β-Cell Mass in Adult Wistar Rats.

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    Piyanard Boonnate

    Full Text Available The amount of dietary monosodium glutamate (MSG is increasing worldwide, in parallel with the epidemics of metabolic syndrome. Parenteral administration of MSG to rodents induces obesity, hyperglycemia, hyperlipidemia, insulin resistance, and type 2 diabetes. However, the impact of dietary MSG is still being debated. We investigated the morphological and functional effects of prolonged MSG consumption on rat glucose metabolism and on pancreatic islet histology.Eighty adult male Wistar rats were randomly subdivided into 4 groups, and test rats in each group were supplemented with MSG for a different duration (1, 3, 6, or 9 months, n=20 for each group. All rats were fed ad libitum with a standard rat chow and water. Ten test rats in each group were provided MSG 2 mg/g body weight/day in drinking water and the 10 remaining rats in each group served as non-MSG treated controls. Oral glucose tolerance tests (OGTT were performed and serum insulin measured at 9 months. Animals were sacrificed at 1, 3, 6, or 9 months to examine the histopathology of pancreatic islets.MSG-treated rats had significantly lower pancreatic β-cell mass at 1, 6 and 9 months of study. Islet hemorrhages increased with age in all groups and fibrosis was significantly more frequent in MSG-treated rats at 1 and 3 months. Serum insulin levels and glucose tolerance in MSG-treated and untreated rats were similar at all time points we investigated.Daily MSG dietary consumption was associated with reduced pancreatic β-cell mass and enhanced hemorrhages and fibrosis, but did not affect glucose homeostasis. We speculate that high dietary MSG intake may exert a negative effect on the pancreas and such effect might become functionally significant in the presence or susceptibility to diabetes or NaCl; future experiments will take these crucial cofactors into account.

  13. Pretreatment with Rhodiola Rosea Extract Reduces Cognitive Impairment Induced by Intracerebroventricular Streptozotocin in Rats: Implication of Anti-oxidative and Neuroprotective Effects

    Institute of Scientific and Technical Information of China (English)

    ZE-QIANG QU; YAN ZHOU; YUAN-SHAN ZENGt; YAN LI; PETER CHUNG

    2009-01-01

    Objectives To investigate the pretreatment effects of Rhodiola rosea (R. rosea) extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer's disease (AD). Methods Male Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin (1.5 mg/kg) on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde (MDA), glutathione reductase (GR) and reduced glutathione (GSH) levels in hippocampus and histopathology of hippocampal neurons. Results The MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract (3.0 g/kg). Conclusion R. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.

  14. Effect of morphine, naloxone and histamine system on water intake in adult male rats.

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    Eidi, Maryam; Oryan, Shahrbanoo; Eidi, Akram; Sepehrara, Leili

    2003-10-08

    The present study investigated the interaction between histamine and opioid systems on water intake in adult male rats. Intracerebroventricular (i.c.v.) injections were carried out in all experiments. Water intake was measured 1 h after drug injections. Administration of histamine (40-80 microg/rat) and naloxone (0.5-1 microg/rat) increased, while morphine (2.5 microg/rat), pyrilamine (25-50 microg/rat), the histamine H1 receptor antagonist, and ranitidine (10-20 microg/rat), the histamine H2 receptor antagonist, decreased water intake in isolated rats. Blockade of histamine H1 and H2 receptors attenuated the histamine-induced response. Pyrilamine, but not ranitidine, increased the inhibitory effect induced by morphine. Also, pharmacological blockade of histamine H1 and H2 receptors decreased the naloxone-induced effect on water intake. It is concluded that the histaminergic system may have a close interaction with morphine and naloxone on drinking behavior.

  15. Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

    Science.gov (United States)

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

    2009-10-01

    N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

  16. Effect of artemether on hematological parameters of healthy and uninfected adult Wistar rats

    Institute of Scientific and Technical Information of China (English)

    Osonuga IO; Osonuga OA; Osonuga A; Onadeko AA; Osonuga AA

    2012-01-01

    Objective: To evaluate the effect of short term artemether administration on some blood parameters in adult male Wistar rats. Methods: Sixty five albino rats with body weight of 190-220 g were used for the four-phased study. The animals were randomly divided into five groups. The first-four groups of 15 rats were further divided into 3 subgroups of 5 rats. The drug was administered orally at sub-optimal, therapeutic, and high doses of 25, 50 and 75 mg/kg bw, respectively to the rats for 1 day, 2 days and 3 days. Blood samples were collected by cardio-puncture from the rats for hematology at the end of each phase. The last group served as control, and they were given water ad libitum. Results:Artemether caused significant reduction (P<0.05) of the hematological profile of the animals in a dose dependent manner. Discontinuation of the drug use however showed gradual recovery of the depressed indices of the blood parameters. Conclusions:The results suggest that artemether can induce reversible changes in hematological profiles of rats by extension man. This can probably aggravate anemia when artemether is administered to malaria patients. Hence, the study supports the use of the drug with caution especially in patients prone to anemic tendencies.

  17. Influence of endogenous ciliary neurotrophic factor on neural differentiation of adult rat hippocampal progenitors

    Institute of Scientific and Technical Information of China (English)

    Jun Ding; Zhili He; Juan Ruan; Ying Liu; Chengxin Gong; Shenggang Sun; Honghui Chen

    2013-01-01

    Ciliary neurotrophic factor is the only known neurotrophic factor that can promote differentiation of hippocampal neural progenitor cells to glial cells and neurons in adult rats. This process is similar to spontaneous differentiation. Therefore, ciliary neurotrophic factor may be involved in spontaneous differentiation of neural stem cells. To verify this hypothesis, the present study isolated neural progenitor cells from adult male rats and cultured them in vitro. Results showed that when neural progenitor cells were cultured in the absence of mitogen fibroblast growth factor-2 or epidermal growth factor, they underwent spontaneous differentiation into neurons and glial cells. Western blot and immunocytochemical staining showed that exogenous ciliary neurotrophic factor strongly induced adult hippocampal progenitor cells to differentiate into neurons and glial cells. Moreover, passage 4 adult hippocampal progenitor cells expressed high levels of endogenous ciliary neurotrophic factor, and a neutralizing antibody against ciliary neurotrophic factor prevented the spontaneous neuronal and glial differentiation of adult hippocampal progenitor cells. These results suggest that the spontaneous differentiation of adult hippocampal progenitor cells is mediated partially by endogenous ciliary neurotrophic factor.

  18. Potential testicular toxicity of sodium nitrate in adult rats.

    Science.gov (United States)

    Aly, Hamdy A A; Mansour, Ahmed M; Abo-Salem, Osama M; Abd-Ellah, Hala F; Abdel-Naim, Ashraf B

    2010-02-01

    Nitrate is a common contaminant in groundwater aquifers. Current study aimed at evaluating the potential testicular toxicity of sodium nitrate in rats. Sodium nitrate was given orally to rats at doses of 50, 100 or 200 mg/kg/day for 60 consecutive days. Sperm count and motility, daily sperm production and testis weight were significantly decreased specially at high doses. Testicular activity of lactate dehydrogenase-X, glucose-6-phosphate dehydrogenase, and acid phosphatase were inhibited in a dose-related manner. Lipid peroxides and hydrogen peroxide production were significantly increased in all treated animals. This was accompanied by inhibition of testicular activities of superoxide dismutase and glutathione peroxidase. Fifty mg/kg of sodium nitrate did not significantly alter catalase or glutathione reductase activity. Glutathione was significantly decreased by sodium nitrate in a dose-related manner. The decrease in sperm count and motility and daily sperm production was confirmed by histopathological studies which indicated chromatolysis, pyknosis and necrosis in spermatocytes. In conclusion, subchronic exposure of rats to sodium nitrate results in testicular toxicity as evidenced by decreased sperm count and motility, daily sperm production and testis weight, inhibited activity of enzyme markers of spermatogenesis and induction of histopathological changes. These effects are attributed, at least partly, to testicular oxidative stress.

  19. Repair of acutely injured spinal cord through constructing tissue-engineered neural complex in adult rats

    Institute of Scientific and Technical Information of China (English)

    PU Yu; GUO Qing-shan; WANG Ai-min; WU Si-yu; XING Shu-xing; ZHANG Zhong-rong

    2007-01-01

    Objective: To construct tissue-engineered neural complex in vitro and study its effect in repairing acutely injured spinal cord in adult rats. Methods: Neural stem cells were harvested from the spinal cord of embryo rats and propagated in vitro. Then the neural stem cells were seeded into polyglycolic acid scaffolds and co-cultured with extract of embryonic spinal cord in vitro. Immunofluorescence histochemistry and scanning electron microscope were used to observe the microstructure of this complex. Animal model of spine semi-transection was made and tissue-engineered neural complex was implanted by surgical intervention. Six weeks after transplantation, functional evaluation and histochemistry were applied to evaluate the functional recovery and anatomic reconstruction. Results: The tissue-engineered neural complex had a distinct structure, which contained neonatal neurons, oligodendrocytes and astrocytes. After tissue-engineered neural complex was implanted into the injured spinal cord, the cell components such as neurons, astrocytes and oligodendrocytes, could survive and keep on developing. The adult rats suffering from spinal cord injury got an obvious neurological recovery in motor skills. Conclusions: The tissue-engineered neural complex appears to have therapeutic effects on the functional recovery and anatomic reconstruction of the adult rats with spinal cord injury.

  20. Effects of Chronic 5-Bromo-2-Deoxyuridine Adminidtration on Spatial Memory in the Adult Rats

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    Mahmoud Hosseini

    2013-05-01

    Full Text Available Background: 5-Bromo-2-deoxyuridine (BrdU has been a principal marker for mitotic cells in studies of adult neurogenesis. The method consists of a pulse injection of BrdU into the intraperitoneal cavity followed by a variable survival time allowing for tracking the divided cells and their progeny. However, such exogenous markers may produce toxic effects. Aim of this study was determined the effects of Brdu on spatial memory in the adult rat. Materials and Methods: 16 Wistar rats were used in this experimental study. The rats were randomly divided into 2 groups (N=8 in each group, as follows: control and Brdu (50 mg/kg. Brdu was administered intraperitoneally for 6 weeks and then animals were used for behavioral testing in the Morris water maze. The data were analyzed with repeated measure’s ANOVA.Results: Our present findings show that there were no differences in the path length, escape latency and swim speed between control and Brdu-administrated groups.Conclusion: This study show that Brdu (exogenic proliferation marker did not has side effects on spatial memory in the adult rats.

  1. Role of histidine/histamine in carnosine-induced neuroprotection during ischemic brain damage.

    Science.gov (United States)

    Bae, Ok-Nam; Majid, Arshad

    2013-08-21

    Urgent need exists for new therapeutic options in ischemic stroke. We recently demonstrated that carnosine, an endogenous dipeptide consisting of alanine and histidine, is robustly neuroprotective in ischemic brain injury and has a wide clinically relevant therapeutic time window. The precise mechanistic pathways that mediate this neuroprotective effect are not known. Following in vivo administration, carnosine is hydrolyzed into histidine, a precursor of histamine. It has been hypothesized that carnosine may exert its neuroprotective activities through the histidine/histamine pathway. Herein, we investigated whether the neuroprotective effect of carnosine is mediated by the histidine/histamine pathway using in vitro primary astrocytes and cortical neurons, and an in vivo rat model of ischemic stroke. In primary astrocytes, carnosine significantly reduced ischemic cell death after oxygen-glucose deprivation, and this effect was abolished by histamine receptor type I antagonist. However, histidine or histamine did not exhibit a protective effect on ischemic astrocytic cell death. In primary neuronal cultures, carnosine was found to be neuroprotective but histamine receptor antagonists had no effect on the extent of neuroprotection. The in vivo effect of histidine and carnosine was compared using a rat model of ischemic stroke; only carnosine exhibited neuroprotection. Taken together, our data demonstrate that although the protective effects of carnosine may be partially mediated by activity at the histamine type 1 receptor on astrocytes, the histidine/histamine pathway does not appear to play a critical role in carnosine induced neuroprotection.

  2. Cross-sensitization between testosterone and cocaine in adolescent and adult rats.

    Science.gov (United States)

    Engi, Sheila A; Cruz, Fabio C; Crestani, Carlos C; Planeta, Cleopatra S

    2015-11-01

    Cocaine and anabolic-androgenic steroids are substances commonly co-abused. The use of anabolic steroids and cocaine has increased among adolescents. However, few studies investigated the consequences of the interaction between anabolic-androgenic steroids in animals' model of adolescence. We examined the effects of acute and repeated testosterone administration on cocaine-induced locomotor activity in adult and adolescent rats. Rats received ten once-daily subcutaneous (s.c.) injections of testosterone (10mg/kg) or vehicle. Three days after the last testosterone or vehicle injections rats received an intraperitoneal (i.p.) challenge injection of either saline or cocaine (10mg/kg). A different subset of rats was treated with a single injection of testosterone (10mg/kg) or vehicle and three days later was challenged with cocaine (10mg/kg, i.p.) or saline. Immediately after cocaine or saline injections the locomotor activity was recorded during forty minutes. Our results demonstrated that repeated testosterone induced locomotor sensitization to cocaine in adolescent but not adult rats.

  3. Effects of extremely low frequency magnetic field on anxiety level and spatial memory of adult rats

    Institute of Scientific and Technical Information of China (English)

    HE Li-hua; SHI Hong-mei; LIU Tong-tong; XUYing-chun; YE Kang-ping; WANG Sheng

    2011-01-01

    Background As the widespread use of electric devices in modern life,human are exposed to extremely low frequency magnetic fields (ELF MF) much more frequently than ever.Over the past decades,a substantial number of epidemiological and experimental studies have demonstrated that ELF MF (50 Hz) exposure is associated with increased risk of various health effects.The present study examined the effects of chronic exposure to ELF MF on anxiety level and spatial memory of adult rats.Methods The 50-Hz ELF MF was used during the whole experimental procedures and the value of magnetic field (MF)was set to 2 mT.Adult rats were divided randomly to control,MF 1 hour and MF 4 hours group.Anxiety-related behaviors were examined in the open field test and the elevated plus maze; changes in spatial learning and memory were determined in Morris water maze after 4 weeks of daily exposure.Results Rats in MF 4 hours group had increased anxiety-like behaviors with unaltered locomotor activity.In the Morris water maze test,rats had reduced latency to find the hidden platform and improved long-term memory of former location of platform without changes in short-term memory and locomotor activity.Conclusion Chronic ELF MF exposure has anxiogenic effect on rats,and the promoting effects on spatial learning and long-term retention of spatial memory.

  4. Enriched experience and recovery from amblyopia in adult rats: impact of motor, social and sensory components.

    Science.gov (United States)

    Baroncelli, Laura; Bonaccorsi, Joyce; Milanese, Marco; Bonifacino, Tiziana; Giribaldi, Francesco; Manno, Ilaria; Cenni, Maria Cristina; Berardi, Nicoletta; Bonanno, Giambattista; Maffei, Lamberto; Sale, Alessandro

    2012-06-01

    Amblyopia is one of the most common forms of visual impairment, arising from an early functional imbalance between the two eyes. It is currently accepted that, due to a lack of neural plasticity,amblyopia is an untreatable pathology in adults. Environmental enrichment (EE) emerged as a strategy highly effective in restoring plasticity in adult animals, eliciting recovery from amblyopia through a reduction of intracortical inhibition. It is unknown whether single EE components are able to promote plasticity in the adult brain, crucial information for designing new protocols of environmental stimulation suitable for amblyopic human subjects. Here, we assessed the effects of enhanced physical exercise,increased social interaction, visual enrichment or perceptual learning on visual function recovery in adult amblyopic rats. We report a complete rescue of both visual acuity and ocular dominance in exercised rats, in animals exposed to visual enrichment and in animals engaged in perceptual learning.These effects were accompanied by a reduced inhibition/excitation balance in the visual cortex. In contrast, we did not detect any sign of recovery in socially enriched rats or in animals practicing a purely associative visual task. These findings could have a bearing in orienting clinical research in the field of amblyopia therapy.

  5. Neonatal nociception elevated baseline blood pressure and attenuated cardiovascular responsiveness to noxious stress in adult rats.

    Science.gov (United States)

    Chu, Ya-Chun; Yang, Cheryl C H; Lin, Ho-Tien; Chen, Pin-Tarng; Chang, Kuang-Yi; Yang, Shun-Chin; Kuo, Terry B J

    2012-10-01

    Neonatal nociception has significant long-term effects on sensory perception in adult animals. Although neonatal adverse experience affect future responsiveness to stressors is documented, little is known about the involvement of early nociceptive experiences in the susceptibility to subsequent nociceptive stress exposure during adulthood. The aim of this study is to explore the developmental change in cardiovascular regulating activity in adult rats that had been subjected to neonatal nociceptive insults. To address this question, we treated neonatal rats with an intraplantar injection of saline (control) or carrageenan at postnatal day 1. The carrageenan-treated rats exhibited generalized hypoalgesia at basal state, and localized hyperalgesia after re-nociceptive challenge induced by intraplantar injections of complete Freund's adjuvant (CFA) as adults. Then we recorded baseline cardiovascular variables and 24-h responsiveness to an injection of CFA in the free-moving adult rats with telemetric technique. The carrageenan-treated rats showed significantly higher basal blood pressures (110.3±3.16 vs. control 97.0±4.28 mmHg). In control animals, baroreceptor reflex sensitivity (BRS) decreased, sympathetic vasomotor activity increased, and parasympathetic activity was inhibited after CFA injection. Blood pressure elevation was evident (107.0±2.75 vs. pre-injection 97.0±4.28 mmHg). Comparatively, the carrageenan-treated rats showed a higher BRS (BrrLF 1.03±0.09 vs. control 0.70±0.06 ms/mmHg) and higher parasympathetic activity [0.93±0.17 vs. control 0.32±0.02 ln(ms²)] after CFA injection. The change in blood pressure is negligible (111.9±4.05 vs. pre-injection 110.3±3.16 mmHg). Our research has shown that neonatal nociception alters future pain sensation, raises basal blood pressure level, and attenuates cardiovascular responsiveness to nociceptive stress in adult rats.

  6. Comparison of airway measurements during influenza-induced tachypnea in infant and adult cotton rats

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    Prince Gregory A

    2009-06-01

    Full Text Available Abstract Background Increased respiratory rate (tachypnea is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital. We previously demonstrated that influenza infection of adult cotton rats (Sigmodon hispidus also results in tachypnea and wanted to establish whether this clinical sign was observed in infected infant cotton rats. We hypothesized that age-dependent differences in lung mechanics result in differences in ventilatory characteristics following influenza infection. Methods Lung tidal volume, dynamic elastance, resistance, and pleural pressure were measured in a resistance and compliance system on mechanically-ventilated anesthestized young (14–28 day old and adult (6–12 week old cotton rats. Animals at the same age were infected with influenza virus, and breathing rates and other respiratory measurements were recorded using a whole body flow plethysmograph. Results Adult cotton rats had significantly greater tidal volume (TV, and lower resistance and elastance than young animals. To evaluate the impact of this increased lung capacity and stiffening on respiratory disease, young and adult animals were infected intra-nasally with influenza A/Wuhan/359/95. Both age groups had increased respiratory rate and enhanced pause (Penh during infection, suggesting lower airway obstruction. However, in spite of significant tachypnea, the infant (unlike the adult cotton rats maintained the same tidal volume, resulting in an increased minute volume. In addition, the parameters that contribute to Penh were different: while relaxation time between breaths and time of expiration was decreased in both age groups, a disproportionate increase in peak inspiratory and expiratory flow contributed to the increase in Penh in infant animals. Conclusion While respiratory rate is increased in both adult and infant influenza-infected cotton rats, the volume of air exchanged per minute (minute volume is

  7. Induction of abnormal oocyte division under the constant light in the young adult rat

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Fangxiong Shi

    2012-01-01

    In order to study the effect of constant light on the ovary, 12 young adult female rats were exposed to constant light for 37 days and their estrous cycles were recorded by daily examination and the ovaries were examined histologically. The results showed that constant light induced in an abnormal and uncontrolled division of oocytes. In these divided-oocyte follicles (DOFs), two or more divided-oocytes shared one zona pellucida and usually floated freely in the follicular antrum. This fantastic phenomenon was discovered for the first time, and it was different from multioocyte follicles (MOFs) and polyovular follicles (POFs) founded in rats, humans, rabbits, mice and dogs.

  8. Evaluation of the neuroprotective effect of ketoprofen on rats submitted to permanent focal brain ischemia Avaliação do efeito neuroprotetor do cetoprofeno em ratos submetidos à isquemia cerebral focal permanente

    Directory of Open Access Journals (Sweden)

    Manoel Nunes da Silva

    2007-12-01

    Full Text Available OBJECTIVE: To study the neurobehavioral, biochemical and histopathological consequences of permanent focal brain ischemia, and the putative neuroprotective action of ketoprofen. METHOD: One-hundred-and-three Wistar rats divided into groups A and B were respectively submitted to 48 hours and 15 days of ischemia. Each group was divided into 4 subgroups: ischemic not treated, ischemic treated, sham not treated, and sham treated. Ischemic animals had the left middle cerebral artery coagulated. Ketoprofen was administered to treated subgroups 15 minutes before arterial coagulation (manipulation in the sham group. RESULTS: Exploratory activity and defecation were reduced in all ischemic animals in the first postoperative days and constant histopathological changes were observed in each group. The total brain glutamate levels were higher in treated animals 48 hours after surgery. CONCLUSION: No clear parallelism among behavioral, biochemical and histopathological findings was observed. Ketoprofen demonstrated no neuroprotective effect on the behavioral or histopathological aspects of focal permanent brain ischemia.OBJETIVO: Estudar as conseqüências comportamentais, bioquímicas e histopatológicas da isquemia cerebral focal permanente e o possível efeito neuroprotetor do cetoprofeno. MÉTODO: Foram utilizados 103 ratos Wistar, divididos em grupos A e B, submetidos, respectivamente, a 48 horas e a 15 dias de isquemia. Cada grupo foi dividido em 4 subgrupos: isquêmico não tratado; isquêmico tratado; sham não tratado; sham tratado. Nos animais isquêmicos foi coagulada a artéria cerebral média esquerda. Os subgrupos tratados receberam cetoprofeno 15 minutos antes da oclusão ou manipulação arterial. RESULTADOS: Os animais isquêmicos reduziram a atividade exploratória e as evacuações nos primeiros dias pós-operatórios e mostraram alterações histopatológicas constantes em cada grupo. As concentrações do glutamato total 48 horas após a

  9. The Neuroprotective Effect of Dark Chocolate in Monosodium Glutamate-Induced Nontransgenic Alzheimer Disease Model Rats: Biochemical, Behavioral, and Histological Studies.

    Science.gov (United States)

    Madhavadas, Sowmya; Kapgal, Vijaya Kumar; Kutty, Bindu M; Subramanian, Sarada

    2016-01-01

    The vulnerability to oxidative stress and cognitive decline continue to increase during both normal and pathological aging. Dietary changes and sedentary life style resulting in mid-life obesity and type 2 diabetes, if left uncorrected, further add to the risk of cognitive decline and Alzheimer disease (AD) in the later stages of life. Certain antioxidant agents such as dietary polyphenols, taken in adequate quantities, have been suggested to improve the cognitive processes. In this study, we examined the effect of oral administration of dark chocolate (DC) containing 70% cocoa solids and 4% total polyphenol content for three months at a dose of 500 mg/Kg body weight per day to 17-month-old monosodium glutamate treated obese Sprague-Dawley rats, earlier characterized as a nontransgenic AD (NTAD) rat model after reversal of obesity, diabetes, and consequent cognitive impairments. The results demonstrated that DC reduced the hyperglycemia, inhibited the cholinesterase activity in the hippocampal tissue homogenates, and improved the cognitive performance in spatial memory related Barnes maze task. Histological studies revealed an increase in cell volume in the DC treated rats in the CA3 region of the hippocampus. These findings demonstrated the benefits of DC in enhancing cognitive function and cholinergic activity in the hippocampus of the aged NTAD rats while correcting their metabolic disturbances.

  10. Concentrations of Nitric Oxide in Rat Brain Tissues after Diffuse Brain Injury and Neuroprotection by the Selective Inducible Nitric Oxide Synthase Inhibitor Aminoguanidine

    Institute of Scientific and Technical Information of China (English)

    Yi-bao Wang; Shao-wu Ou; Guang-yu Li; Yun-hui Liu

    2005-01-01

    @@ To investigate the effects of nitric oxide (NO) and the selective inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (AG) on trauma, we explored the concentrations of nitric oxide in rat brain tissues at different time stamps after diffuse brain injury (DBI) with or without AG treatment.

  11. Insulin Neuroprotection and the Mechanisms

    Institute of Scientific and Technical Information of China (English)

    Li-Yun Yu; Yu Pei

    2015-01-01

    Objective:To analyze the mechanism of neuroprotection of insulin and which blood glucose range was benefit for insulin exerting neuroprotective action.Data Sources:The study is based on the data from PubMed.Study Selection:Articles were selected with the search terms "insulin","blood glucose","neuroprotection","brain","glycogen","cerebral ischemia","neuronal necrosis","glutamate","γ-aminobutyric acid".Results:Insulin has neuroprotection.The mechanisms include the regulation of neurotransmitter,promoting glycogen synthesis,and inhibition of neuronal necrosis and apoptosis.Insulin could play its role in neuroprotection by avoiding hypoglycemia and hyperglycemia.Conclusions:Intermittent and long-term infusion insulin may be a benefit for patients with ischemic brain damage at blood glucose 6-9 mmol/L.

  12. Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny.

    Science.gov (United States)

    Garoui, El Mouldi; Troudi, Afef; Fetoui, Hamadi; Soudani, Nejla; Boudawara, Tahia; Zeghal, Najiba

    2012-11-01

    The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl(2) in drinking water; group 3 received 350 ppm CoCl(2) in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity. Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period.

  13. Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats.

    Science.gov (United States)

    Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

    2015-12-01

    We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14-18 months of age) and 14 young adult (2.5-6.5 months of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes.

  14. Resveratrol improves reproductive parameters of adult rats varicocelized in peripuberty.

    Science.gov (United States)

    Mendes, Talita Biude; Paccola, Camila Cicconi; de Oliveira Neves, Flávia Macedo; Simas, Joana Noguères; da Costa Vaz, André; Cabral, Regina Elisabeth L; Vendramini, Vanessa; Miraglia, Sandra Maria

    2016-07-01

    The aim of this study was to investigate the protective action of resveratrol against the reproductive damage caused by left-sided experimental varicocele. There was a reduction of testicular major axis in the varicocele group when compared with the other groups; the testicular volume was reduced in varicocele group in comparison to the sham-control and resveratrol groups. The frequency of morphologically abnormal sperm was higher in varicocele and varicocele treated with resveratrol groups than in sham-control and resveratrol groups. The frequency of sperm with 100% of mitochondrial activity and normal acrosome integrity were lower in varicocele group than in varicocele treated with resveratrol, sham-control and resveratrol groups. Sperm motility was also reduced in varicocele group than in other groups. The sperm DNA fragmentation was higher in varicocele group than in other groups. Testicular levels of malondialdehyde were higher in varicocele and varicocele treated with resveratrol groups. The varicocele and varicocele treated with resveratrol groups had a significantly higher frequency of TUNEL-positive cells than sham-control and resveratrol groups; however, immunolabeling of the testes from varicocele treated with resveratrol group showed a lower number of apoptotic germ cells in comparison with the left testis of rats of the varicocele group. Reproductive alterations produced by varicocele from peripuberty were reduced by resveratrol in adulthood. Resveratrol should be better investigated as an adjuvant in the treatment of varicocele. Daily administration of resveratrol to rats with varicocele from peripuberty improves sperm quality in the adulthood.

  15. The N-methyl-D-aspartate antagonist, MK-801, fails to protect against neuronal damage caused by transient, severe forebrain ischemia in adult rats.

    Science.gov (United States)

    Buchan, A; Li, H; Pulsinelli, W A

    1991-04-01

    The neuroprotective effects of dizocilipine maleate (MK-801), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor/channel, were tested in the 4-vessel occlusion rat model of forebrain ischemia. Adult Wistar rats, treated intraperitoneally with MK-801 or saline using several different treatment paradigms were subjected to 5 (n = 208) or 15 (n = 62) min of severe, transient forebrain ischemia. In saline-treated animals, 15 min of ischemia (n = 13) produced extensive and consistent loss of pyramidal neurons in the CA1 zone of hippocampus. The degree and distribution of cell loss were not reduced by single dose preischemic administration of MK-801 at 1 (n = 7), 2.5 (n = 4), or 5 mg/kg (n = 8). In other animals subjected to 15 min of forebrain ischemia, multiple doses of MK-801 (5, 2.5, and 2.5 mg/kg) given immediately and at approximately 8 and 20 hr after cerebral reperfusion (n = 5) did not alter CA1 injury compared to saline-treated controls (n = 5). Five minutes of forebrain ischemia in saline-treated animals, (n = 82) resulted in significantly fewer (p less than 0.001) dead CA1 pyramidal cells and a greater variance compared to animals subjected to 15 min of ischemia. Power analysis of the preliminary saline-treated animals subjected to 5 min of ischemia (n = 22) indicated that 60 animals per group were necessary to detect a 15% difference between MK-801 and vehicle-treated groups. Multidose treatment with MK-801 (1 mg/kg) given 1 hr prior to 5 min of ischemia (n = 60) and again at approximately 8 and 16 hr after recirculation failed to attenuate hippocampal injury.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Electrophysiology of embryonic, adult and aged rat hippocampal neurons in serum-free culture.

    Science.gov (United States)

    Evans, M S; Collings, M A; Brewer, G J

    1998-01-31

    Methods were recently developed for culturing neurons from adult rat hippocampus using the serum-free medium Neurobasal with B27 supplement. To determine whether adult cultured neurons have normal electrical properties, we studied cultures from rats of three age groups: (1) embryonic; (2) 10-11 months old and (3) 35-36 months old. Neurons had a polarized morphology with a large branching apical dendrite and small basal dendrites. Mean resting potentials were similar in the three age groups. All neurons had nonlinear current-voltage relationships, indicating the presence of voltage-sensitive ion channels. Most neurons had a voltage-sensitive inward current followed by a sustained voltage-sensitive outward current. Tetrodotoxin blocked the inward current, which is likely to be a sodium current. The sustained outward current, which is likely to be a potassium current, reversed at -71 mV. Most neurons exhibited anomalous rectification. Calcium currents were present in both embryonic and adult neurons. Embryonic neurons would sometimes fire multiple action potentials but adult neurons fired only single action potentials. Our results indicate that both embryonic and adult cultured neurons retain a clearly neuronal electrophysiological phenotype in Neurobasal/B27 serum-free medium.

  17. Effect of the antioxidant dibunol on adrenocortical, thyroid, and adenohypopyseal function in adult and old rats

    Energy Technology Data Exchange (ETDEWEB)

    Gorban' , E.N.

    1986-04-01

    This paper studies the effect of dibunol (4-methyl-2,6-di-tert-butylphenol) (D) on the function of the adrenal cortex, thyroid gland, and adenhypophysis, which produces trophic hormones for the other two glands. Experiments were carried out on adult rats. After injection of D concentrations of corticosterone (CS), triodothyronine (T/sub 3/), ACTH, and thyrotrophin (TSH) in the blood plasma and the CS concentration in tssue of the adenohypophysis were determined. It is shown that injection of D caused biphasic changes in the CS concentration in both tissues studied in adult and old animals.

  18. Temporal Expression of Mutant LRRK2 in Adult Rats Impairs Dopamine Reuptake

    Directory of Open Access Journals (Sweden)

    Hongxia Zhou, Cao Huang, Jianbin Tong, Weimin C Hong, Yong-Jian Liu, Xu-Gang Xia

    2011-01-01

    Full Text Available Parkinson's disease (PD results from progressive degeneration of dopaminergic neurons. Most PD cases are sporadic, but some have pathogenic mutation in the individual genes. Mutation of the leucine-rich repeat kinase-2 (LRRK2 gene is associated with familial and sporadic PD, as exemplified by G2019S substitution. While constitutive expression of mutant LRRK2 in transgenic mice fails to induce neuron death, transient expression of the disease gene by viral delivery causes a substantial loss of dopaminergic neurons in mice. To further assess LRRK2 pathogenesis, we created inducible transgenic rats expressing human LRRK2 with G2019S substitution. Temporal overexpression of LRRK2G2019S in adult rats impaired dopamine reuptake by dopamine transporter (DAT and thus enhanced locomotor activity, the phenotypes that were not observed in transgenic rats constitutively expressing the gene throughout life time. Reduced DAT binding activity is an early sign of dopaminergic dysfunction in asymptomatic subjects carrying pathogenic mutation in LRRK2. Our transgenic rats recapitulated the initiation process of dopaminergic dysfunction caused by pathogenic mutation in LRRK2. Inducible transgenic approach uncovered phenotypes that may be obscured by developmental compensation in constitutive transgenic rats. Finding in inducible LRRK2 transgenic rats would guide developing effective strategy in transgenic studies: Inducible expression of transgene may induce greater phenotypes than constitutive gene expression, particularly in rodents with short life time.

  19. Effects of cyclophosphamide on the kaolin consumption (pica behavior) in five strains of adult male rats.

    Science.gov (United States)

    Tohei, Atsushi; Kojima, Shu-ichi; Ikeda, Masashi; Hokao, Ryoji; Shinoda, Motoo

    2011-07-01

    It is known that pica, the consumption of non-nutritive substances such as kaolin, can be induced by administration of toxins or emetic agents in rats. In the present study, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior and on the concentration of 5-hydroxyindoleacetic acids (5HIAA) in cerebrospinal fluid (CSF) in the following five strains of adult male rats: Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) into the rats and kaolin and food intake were measured at 24 hr after injection. The animals were anesthetized with urethane (1 g/kg) at 3 hr after injection of cyclophosphamide, and CSF was collected from the cisterna magna. WI and LE rats clearly showed pica behavior as compared with the other strains. In LE rats, the concentration of 5HIAA in CSF also increased in a dose-dependent manner of cyclophosphamide. The pretreatment with ondansetron (5-HT(3) antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide, that pica induced by cyclophosphamide mimics many aspects of emesis including the serotonergic response in the central nervous system and that use of the pica model would be a practical method for evaluating the effects of antiemetic drugs in addition to the mechanism of emesis.

  20. Impairment in Spatial Memory in adult Rats following developmental Low Lead Exposure

    Directory of Open Access Journals (Sweden)

    Rajashekar Rao Barkur

    2012-11-01

    Full Text Available The present study was aimed to investigate the effect of environmentally relevant levels of lead exposure during gestational and early postnatal period on hippocampal dependent spatial memory in rats during adulthood. The pregnant rats were allowed to drink either normal water (control group or 0.2% lead acetate solution (Leadtreated group during pregnancy and lactation. Thus rats pups of lead treated group where exposed to lead indirectly through their mothers during this period. At weaning pups of lead treated group were allowed to drink normal water till they attain the adult hood. Blood lead level was estimated on postnatal day 22 and 120. Birth weight and weight gain of the rat pups as they grew were measured at regular intervals. Both the control and lead treated groups of rats were subjected to water maze test on postnatal day 30 and 120. Results showed that lead treatment had no effect on birth weight or weight gain. Blood lead level on postnatal day 22 was significantly high in treated group compared to the control group and it was normalized by end of four months. The rats born to lead treated mothers showed impaired in spatial memory during water maze test both on postnatal day 36 and 126. These data suggests that exposure to environmentally relevant levels of lead during intrauterine and early postnatal period of brain development causes impairment in spatial memory not only during infancy but also lasts till adulthood.

  1. Adolescent social defeat disturbs adult aggression-related impulsivity in wild-type rats.

    Science.gov (United States)

    Coppens, Caroline M; Coolen, Alex; de Boer, Sietse F; Koolhaas, Jaap M

    2014-10-01

    Adolescence is generally considered as a developmental period during which adverse social experiences may have lasting consequences in terms of an increased vulnerability to affective disorders. This study aimed at determining the individual susceptibility to adolescent social stress using a rat model. We used rats of the Wild-type Groningen strain, which are characterized by a broad variation in adult levels of aggression and impulsivity. We hypothesized that experience of social defeat in adolescence results in heightened aggression and impulsivity levels in adulthood. In contrast to our expectation, adolescent social defeat did not lead to a difference in the average adult level of aggression and impulsivity, but the significant correlation between offensive aggression and impulsivity found in control animals was not present in animals defeated during adolescence.

  2. Retrograde Labeling of Adult Rat Retinal Ganglion Cells with the Flurogold

    Institute of Scientific and Technical Information of China (English)

    Wei Huang; Yannian Hui; Miaoli Zhang

    2000-01-01

    Purpose: To study the densities and distribution of retinal ganglion cells(RGC) in adult rat retinae with flurogold(FG) labeling retogradely.Methods: FG was injected to the superior colliculi(SC) and dorsal lateral geniculate nuclei (dLGN) in adult rats and the retinae were examined by fluorescence microscopy at various periods of time.Results: FG-labelled RGC were observed in the retina as early as 3 days after application of FG. The labelled cells gradually increased in density, reached 95% of the maximal number on days 7 and the maximal number on days 30. The density of labelled cells was higher in the posterior pole than in the peripheral area. The fluorescence intensity in labelled cells maintained up to 60 days.Conclusion: The FG retrograde labeling method is reliable and effective for quantity of RGC. Eye Science 2000; 16:29 ~ 33.

  3. Retrograde Labeling of Adult Rat Retinal Ganglion Cells with the Flurogold

    Institute of Scientific and Technical Information of China (English)

    WeiHuang; YannianHui; 等

    2002-01-01

    Purpose:To study the densities and distribution of retinal ganglion cells(RGC) in adult rat retinae with flurogold(FG) labeling retogradely.Methods:FG was injected to the superior colliculid(SC) and dorsal lateral geniculate nuclei(dLGN) in adult rats and the retinae were examined by fluorescence microscopy at various periods of time.Results:FG-labelled RGC were observed in the retina as early as 3 days after application of FG.The labeled cells gradually increased in density,reached 95% of the maximal number on days 7 and the maximal nuber on days 30.The density of labeled cells was higher in the posterior pole than in the peripheral area.The fluorescence intensity in labeled cells maintained up to 60 days.Conclusion:The FG retrograde labeling method is reliable and effective for quantity of RGC.Eye Science 2000;46:29-33.

  4. Immunohistochemical localization of glutamate transporter EAAC1 in the brainstem of adult rat

    Institute of Scientific and Technical Information of China (English)

    ZHANG Fu-xing; LIU Tao; ZHAO Jing-wei; LI Jin-lian; DONG Yu-lin; LI Ji-shuo

    2001-01-01

    Objective: To observe the distribution of EAAC1, a subtype of glutamate transporters, in the brainstem of adult rat. Methods: Immunocytochemical staining with avidin-biotin complex (ABC) method was employed. Results:EAAC1 was widely distributed throughout the brainstem. In many regions, the EAAC1-like immunoreactivity was primarily distributed in the neuropil. Cell body staining was observed in the prepositus hypoglossal nucleus, external cortex of the inferior colliculus, red nucleus, substantia nigra, mesencephalic raphe nuclei, ventral tegmental nucleus, superior olivary complex, nucleus of the trapezoid body, cochlear nucleus, sensory trigeminal complex, Barrington's nucleus,trigeminal motor nucleus, parabrachial nuclei, dorsal nucleus of vagus, hypoglossal nucleus, locus coeruleus, lateral and superior vestibular nuclei, lateral paragigantocellular nucleus and dorsal paragigantocellular nucleus. Conclusion: Glutamate transporter EAAC 1 is widely distributed throughout the brainstem of adult rat, which may play an important role in excitatory activities of the neurons induced by glutamate.

  5. Toxicity Induced after Subchronic Administration of the Synthetic Food Dye Tartrazine in Adult Rats, Role of Oxidative Stress

    OpenAIRE

    Narges El Golli; Ines Bini-Dhouib; Aicha Jrad; Imene Boudali; Basma Nasri; Nadia Belhadjhmida; Saloua El Fazaa

    2016-01-01

    The present study was conducted to evaluate the toxic potential of tartrazine, a food color, in different tissues in adult rat: blood, liver, kidneys, and spleen. Tartrazine was administered orally at a dose of 300 mg/kg of body weight to adult male Wistar rats during a period of 30 days. Tartrazine treatment led to an increase in platelets count, a reduction in peripheral lymphocytes and in spleen T CD8-lymphocytes. Furthermore, tartrazine increased the activities of hepatocellular enzymes a...

  6. Differentiation of endogenous neural precursors following spinal cord injury in adult rats

    Institute of Scientific and Technical Information of China (English)

    Bin Zhao; Hua Han; Shuanke Wang; Bingren Gao; Zhengyi Sun

    2008-01-01

    BACKGROUND:Studies have shown that cell death can activate proliferation of endogenous neural stem cells and promote newly generated cells to migrate to a lesion site.OBJECTIVE:To observe regeneration and differentiation of neural cells following spinal cord injury in adult rats and to quantitatively analyze the newly differentiated cells.DESIGN,TIME AND SETTING:A cell biology experiment was performed at the Institute of Orthopedics and Medical Experimental Center,Lanzhou University.between August 2005 and October 2007.MATERIALS:Fifty adult,Wistar rats of both sexes;5-bromodeoxyuridine(BrdU,Sigma,USA);antibodies against neuron-specific enolase,glial fibrillary acidic protein,and myelin basic protein(Chemicon,USA).METHODS:Twenty-five rats were assigned to the spinal cord injury group and received a spinal cord contusion injury.Materials were obtained at day 1,3,7,15,and 29 after injury,with 5 rats for each time point.Twenty-five rats were sham-treated by removing the lamina of the vertebral arch without performing a contusion.MAIN OUTCOME MEASURES:The phenotype of BrdU-labeled cells,i.e.,expression and distribution of surface markers for neurons(neuron-specific enolase),astrocytes(glial fibrillary acidic protein),and oligodendrocytes(myelin basic protein),were identified with immunofluorescence double-labeling.Confocal microscopy was used to detect double-labeled cells by immunofluorescence.Quantitative analysis of newly generated cells was performed with stereological counting methods.RESULTS:There was significant cell production and differentiation after adult rat spinal cord injury.The quantity of newly-generated BrdU-labeled cells in the spinal cord lesion was 75-fold greater than in the corresponding area of control animals.Endogenous neural precursor cells differentiated into astrocytes and oligodendrocytes,however spontaneous neuronal difierentiation was not detected.Between 7 and 29 d after spinal cord injury,newly generated cells expressed increasingly more

  7. Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose.

    Science.gov (United States)

    Abraham, Pretty Mary; Kuruvilla, Korah P; Mathew, Jobin; Malat, Anitha; Joy, Shilpa; Paulose, C S

    2010-09-25

    Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. The present study was carried out to find the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT(2A) receptor subtype, gene expression studies on 5-HT(2A), 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed a significant decrease (p Pyridoxine treated in combination with insulin and A. marmelose to diabetic rats reversed the 5-HT content, B(max), Kd of 5-HT, 5-HT(2A) and gene expression of 5-HT(2A), 5-HTT and INSR in hippocampus to near control. The gene expression of 5-HT(2A) and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin through its transporter significantly increased (p anxiety-related traits in diabetic rats which were corrected by combination therapy. Our results suggest that pyridoxine treated in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal serotonergic function. This has clinical significance in the management of diabetes.

  8. Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose

    Directory of Open Access Journals (Sweden)

    Joy Shilpa

    2010-09-01

    Full Text Available Abstract Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. The present study was carried out to find the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT2A receptor subtype, gene expression studies on 5-HT2A, 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed a significant decrease (p p max and Kd showed a significant decrease (p 2A receptor binding parameters Bmax showed a significant decrease (p p d in hippocampus of diabetic rats compared to control. Gene expression studies of 5-HT2A, 5-HTT and INSR in hippocampus showed a significant down regulation (p A. marmelose to diabetic rats reversed the 5-HT content, Bmax , Kd of 5-HT, 5-HT2A and gene expression of 5-HT2A, 5-HTT and INSR in hippocampus to near control. The gene expression of 5-HT2A and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin through its transporter significantly increased (p A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal serotonergic function. This has clinical significance in the management of diabetes.

  9. 20-Hydroxyeicosatetraenoic Acid Inhibition by HET0016 Offers Neuroprotection, Decreases Edema, and Increases Cortical Cerebral Blood Flow in a Pediatric Asphyxial Cardiac Arrest Model in Rats.

    Science.gov (United States)

    Shaik, Jafar Sadik B; Poloyac, Samuel M; Kochanek, Patrick M; Alexander, Henry; Tudorascu, Dana L; Clark, Robert Sb; Manole, Mioara D

    2015-11-01

    Vasoconstrictive and vasodilatory eicosanoids generated after cardiac arrest (CA) may contribute to cerebral vasomotor disturbances and neurodegeneration. We evaluated the balance of vasodilator/vasoconstrictor eicosanoids produced by cytochrome P450 (CYP) metabolism, and determined their role on cortical perfusion, functional outcome, and neurodegeneration after pediatric asphyxial CA. Cardiac arrest of 9 and 12 minutes was induced in 16- to 18-day-old rats. At 5 and 120 minutes after CA, we quantified the concentration of CYP eicosanoids in the cortex and subcortical areas. In separate rats, we inhibited 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis after CA and assessed cortical cerebral blood flow (CBF), neurologic deficit score, neurodegeneration, and edema. After 9 minutes of CA, vasodilator eicosanoids markedly increased versus sham. Conversely, after 12 minutes of CA, vasoconstrictor eicosanoid 20-HETE increased versus sham, without compensatory increases in vasodilator eicosanoids. Inhibition of 20-HETE synthesis after 12 minutes of CA decreased cortical 20-HETE levels, increased CBF, reduced neurologic deficits at 3 hours, and reduced neurodegeneration and edema at 48 hours versus vehicle-treated rats. In conclusion, cerebral vasoconstrictor eicosanoids increased after a pediatric CA of 12 minutes. Inhibition of 20-HETE synthesis improved cortical perfusion and short-term neurologic outcome. These results suggest that alterations in CYP eicosanoids have a role in cerebral hypoperfusion and neurodegeneration after CA and may represent important therapeutic targets.

  10. Neurones in the adult rat anterior medullary velum.

    Science.gov (United States)

    Ibrahim, M; Menoud, P A; Celio, M R

    2000-03-27

    The presence of neurones in the rat anterior medullary velum (AMV) has been investigated by using antibodies to the calcium-binding proteins, parvalbumin (PV), calretinin (CR), and calbindin-D28k (CB). Disparate populations of mainly GABAergic neurones were located in the rostral and caudal regions of the AMV. The rostral region of the AMV was characterised by GABAergic CR-labelled or PV-labelled neurones. CR-labelled neurones were bipolar or multipolar with round to ovoid somata (diameters between 8 and 12 microm), and rostrocaudally running dendrites forming a network. PV-labelled neurones had round somata (diameters between 6 and 10 microm) and were bi-tufted, with beaded dendrites. Both CR-labelled and PV-labelled dendrites formed punctate pericellular associations with unlabelled somatic profiles. In the caudal region of the AMV, PV-labelled neurones were GABAergic, multipolar cells, having round somata (diameters between 9 and 12 microm), with either beaded or nonbeaded dendrites forming a network of interconnecting dendrites. PV-labelled pericellular associations were made around both PV-labelled and unlabelled somatic profiles. CR labelled unipolar brush cells (UBCs) were not GABAergic. UBCs were characterised by a round to oval somata (10-15 microm in diameter) from which a single primary dendrite emerged to form a distal expansion having small terminal dendrites. From the distal expansion, there also appeared to be CR-labelled processes emanating and extending for up to 250 microm. CB occasionally labelled "Purkinje-like cells" (PLCs). The rat AMV is a more complex structure than first envisaged with the presence of predominantly inhibitory neurones expressing different calcium-binding proteins. Functional and anatomic aspects of this circuitry are further discussed.

  11. Effect of Camphor on Pituitary-Gonadal Hormonal Axis and Oogenesis in Adult Female Rats

    OpenAIRE

    Habibollah Johari; Amir Ashkan Mahjoor; Siyamak Fallahi; Hossein Kargar Jahromi; Maryam Abedini; Mohammad Ali Poor Danesh; Zahra Zamani

    2013-01-01

    Background & Objective: Camphor stimulates the nervous system and the circulatory system, reduces lactation, and prevents conception and embryo embedding. We investigated the effects of camphor on the pituitary-gonadal hormonal axis and concentration of steroidal hormones.   Materials & Methods: The parameters investigated were concentrations of LH, FSH, estrogen, progesterone, and testosterone. Forty adult female rats at a mean weight of 180 ± 20 grams were divided into five groups. Camphor ...

  12. Selection of medium for serum-free primary culture of adult rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Miyazaki,Masahiro

    1990-02-01

    Full Text Available To select a suitable medium for serum-free primary culture of adult rat hepatocytes, ten commercially-available synthetic media were compared for their ability to maintain the cells under serum-free and serum-supplemented conditions with special reference to attachment, survival and albumin secretion. It was found that Williams' medium E and DM-160 medium were the best among the ten media for maintaining hepatocytes under serum-free conditions in primary culture.

  13. Use of the light/dark test for anxiety in adult and adolescent male rats.

    Science.gov (United States)

    Arrant, Andrew E; Schramm-Sapyta, Nicole L; Kuhn, Cynthia M

    2013-11-01

    The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28-34) and adult (PN67-74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-β-carboline-3-carboxamide (FG-7142) and the α₂ adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence.

  14. Methylmercury chloride damage to the adult rat hippocampus cannot be detected by proton magnetic resonance spectroscopy

    Institute of Scientific and Technical Information of China (English)

    Zhiyan Lu; Jinwei Wu; Guangyuan Cheng; Jianying Tian; Zeqing Lu; Yongyi Bi

    2014-01-01

    Previous studies have found that methylmercury can damage hippocampal neurons and accord-ingly cause cognitive dysfunction. However, a non-invasive, safe and accurate detection method for detecting hippocampal injury has yet to be developed. This study aimed to detect methylmer-cury-induced damage on hippocampal tissue using proton magnetic resonance spectroscopy. Rats were given a subcutaneous injection of 4 and 2 mg/kg methylmercury into the neck for 50 consecutive days. Water maze and pathology tests confirmed that cognitive function had been impaired and that the ultrastructure of hippocampal tissue was altered after injection. The results of proton magnetic resonance spectroscopy revealed that the nitrogen-acetyl aspartate/creatine, choline complex/creatine and myoinositol/creatine ratio in rat hippocampal tissue were unchanged. Therefore, proton magnetic resonance spectroscopy can not be used to determine structural damage in the adult rat hippocampus caused by methylmercury chloride.

  15. Localization of Sonic hedgehog secreting and receiving cells in the developing and adult rat adrenal cortex.

    Science.gov (United States)

    Guasti, Leonardo; Paul, Alex; Laufer, Ed; King, Peter

    2011-04-10

    Sonic hedgehog signaling was recently demonstrated to play an important role in murine adrenal cortex development. The organization of the rat adrenal differs from that of the mouse, with the zona glomerulosa and zona fasciculata separated by an undifferentiated zone in the rat, but not in the mouse. In the present study we aimed to determine the mRNA expression patterns of Sonic hedgehog and the hedgehog signaling pathway components Patched-1 and Gli1 in the developing and adult rat adrenal. Sonic hedgehog expression was detected at the periphery of the cortex in cells lacking CYP11B1 and CYP11B2 expression, while signal-receiving cells were localized in the overlying capsule mesenchyme. Using combined in situ hybridization and immunohistochemistry we found that the cells expressing Sonic hedgehog lie between the CYP11B2 and CYP11B1 layers, and thus Sonic hedgehog expression defines one cell population of the undifferentiated zone.

  16. Low-intensity treadmill exercise and/or bright light promote neurogenesis in adult rat brain

    Institute of Scientific and Technical Information of China (English)

    Sung Jin Kwon; Jeongsook Park; So Yun Park; Kwang Seop Song; Sun Tae Jung; So Bong Jung; Ik Ryeul Park; Wan Sung Choi; Sun Ok Kwon

    2013-01-01

    The hippocampus is a brain region responsible for learning and memory functions. The purpose of this study was to investigate the effects of low-intensity exercise and bright light exposure on neurogenesis and brain-derived neurotrophic factor expression in adult rat hippocampus. Male Sprague-Dawley rats were randomly assigned to control, exercise, light, or exercise + light groups (n = 9 per group). The rats in the exercise group were subjected to treadmill exercise (5 days per week, 30 minutes per day, over a 4-week period), the light group rats were irradiated (5 days per week, 30 minutes per day, 10 000 lx, over a 4-week period), the exercise + light group rats were subjected to treadmill exercise in combination with bright light exposure, and the control group rats remained sedentary over a 4-week period. Compared with the control group, there was a significant increase in neurogenesis in the hippocampal dentate gyrus of rats in the exercise, light, and exercise + light groups. Moreover, the expression level of brain-derived neurotrophic factor in the rat hippocampal dentate gyrus was significantly higher in the exercise group and light group than that in the control group. Interestingly, there was no significant difference in brain-derived neurotrophic factor expression between the control group and exercise + light group. These results indicate that low-intensity treadmill exercise (first 5 minutes at a speed of 2 m/min, second 5 minutes at a speed of 5 m/min, and the last 20 minutes at a speed of 8 m/min) or bright-light exposure therapy induces positive biochemical changes in the brain. In view of these findings, we propose that moderate exercise or exposure to sunlight during childhood can be beneficial for neural development.

  17. Qualitative and quantitative analysis of bones in adult rats by repeated intraperitoneal administration of paclitaxel (taxol) using radioisotope EDXRF technique

    Energy Technology Data Exchange (ETDEWEB)

    Oezdemir, Y. E-mail: yozdemir25@yahoo.com; Iyiguen, Ibrahim; Durak, Ridvan

    2003-05-15

    Energy dispersive X-ray fluorescence analysis of right back leg bone samples taken from adult female rats administered paclitaxel (taxol) was carried out using standard addition method. Because qualitative and quantitative data analysis of rat bone samples is not found in the literature, comparison was not made with other experimental results. Our experimental results are presented and discussed in this study.

  18. Methods to evaluate functional nerve recovery in adult rats : walking track analysis, video analysis and the withdrawal reflex

    NARCIS (Netherlands)

    Dijkstra, [No Value; Meek, MF; Robinson, PH; Gramsbergen, A

    2000-01-01

    The aim of this study was to compare different methods for the evaluation of functional nerve recovery. Three groups of adult male Wistar rats were studied. In group A, a 12-mm gap between nerve ends was bridged by an autologous nerve graft; in rats of group B we performed a crush lesion of the scia

  19. A method for unit recording in the lumbar spinal cord during locomotion of the conscious adult rat

    DEFF Research Database (Denmark)

    Berg, Rune W; Chen, Ming-Teh; Huang, Hsueh-Chen;

    2009-01-01

    Extracellular recordings from single units in the brain, for example the neocortex, have proven feasible in moving, awake rats, but have not yet been possible in the spinal cord. Single-unit activity during locomotor-like activity in reduced preparations from adult cats and rats have provided...

  20. Behavioral Differences Between Late Preweanling and Adult Female Sprague-Dawley Rat Exploration of Animate and Inanimate Stimuli and Food

    OpenAIRE

    Smith, Kiersten S.; Morrell, Joan I.

    2010-01-01

    The late preweanling rat has potential as a preclinical model for disorders initially manifested in early childhood that are characterized by dysfunctional interactions with specific stimuli (e.g., obsessive-compulsive disorder and autism). No reports, however, of specific-stimulus exploration in the late preweanling rat are found in the literature. We examined the behavioral responses of normal late preweanling (PND 18-19) and adult rats when presented with exemplars of categorically-varied ...

  1. Cardiac and plasma lipid profiles in response to acute hypoxia in neonatal and young adult rats

    Directory of Open Access Journals (Sweden)

    Raff Hershel

    2010-01-01

    Full Text Available Abstract Background The physiological and biochemical responses to acute hypoxia have not been fully characterized in neonates. Fatty acids and lipids play an important role in most aspects of cardiac function. Methods We performed comprehensive lipid profiling analysis to survey the changes that occur in heart tissue and plasma of neonatal and young adult rats exposed to hypoxia for 2 h, and following 2 h of recovery from hypoxia. Results Cardiac and plasma concentrations of short-chain acylcarnitines, and most plasma long-chain fatty acids, were decreased in hypoxic neonates. Following recovery from hypoxia, concentrations of propionylcarnitine, palmitoylcarnitine, stearoylcarnitine were increased in neonatal hearts, while oleylcarnitine and linoleylcarnitine concentrations were increased in neonatal plasma. The concentrations of long-chain fatty acids and long-chain acylcarnitines were increased in the hearts and plasma of hypoxic young adult rats; these metabolites returned to baseline values following recovery from hypoxia. Conclusion There are differential effects of acute hypoxia on cardiac and plasma lipid profiles with maturation from the neonate to the young adult rat. Changes to neonatal cardiac and plasma lipid profiles during hypoxia likely allowed for greater metabolic and physiologic flexibility and increased chances for survival. Persistent alterations in the neonatal cardiac lipid profile following recovery from hypoxia may play a role in the development of rhythm disturbances.

  2. Effects of estradiol and methoxychlor on Leydig cell regeneration in the adult rat testis.

    Science.gov (United States)

    Chen, Bingbing; Chen, Dongxin; Jiang, Zheli; Li, Jingyang; Liu, Shiwen; Dong, Yaoyao; Yao, Wenwen; Akingbemi, Benson; Ge, Renshan; Li, Xiaokun

    2014-05-06

    The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7-15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms.

  3. Effects of Estradiol and Methoxychlor on Leydig Cell Regeneration in the Adult Rat Testis

    Directory of Open Access Journals (Sweden)

    Bingbing Chen

    2014-05-01

    Full Text Available The objective of the present study is to determine whether methoxychlor (MXC exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2. Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control, 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7–15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms.

  4. Imipramine reverses alterations in cytokines and BDNF levels induced by maternal deprivation in adult rats.

    Science.gov (United States)

    Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Ribeiro, Karine F; Petronilho, Fabrícia; Vuolo, Francieli; Colpo, Gabriela D; Pfaffenseller, Bianca; Kapczinski, Flávio; Dal-Pizzol, Felipe; Quevedo, João

    2013-04-01

    A growing body of evidence is pointing toward an association between immune molecules, as well brain-derived neurotrophic factor (BDNF) and the depression. The present study was aimed to evaluate the behavioral and molecular effects of the antidepressant imipramine in maternally deprived adult rats. To this aim, maternally deprived and non-deprived (control group) male rats were treated with imipramine (30mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming test. In addition to this, IL-10, TNF-α and IL-1β cytokines were assessed in the serum and cerebrospinal fluid (CSF). In addition, BDNF protein levels were assessed in the prefrontal cortex, hippocampus and amygdala. In deprived rats treated with saline was observed an increase on immobility time, compared with non-deprived rats treated with imipramine (pimipramine treatment reversed the effects of maternal deprivation on BDNF and cytokines levels (pimipramine, it is suggested that classic antidepressants could exert their effects by modulating the immune system.

  5. Repeated-dose liver micronucleus test of 4,4'-methylenedianiline using young adult rats.

    Science.gov (United States)

    Sanada, Hisakazu; Koyama, Naomi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    Liver micronucleus (MN) tests using partial hepatectomized rats or juvenile rats have been shown to be useful for the detection of hepatic carcinogens. Moreover, Narumi et al. established the repeated-dose liver MN test using young adult rats for integration into general toxicity. In the present study, in order to examine the usefulness of the repeated-dose liver MN test, we investigated MN induction with a 14 or 28 day treatment protocol using young adult rats treated with 4,4′-methylenedianiline (MDA), a known hepatic carcinogen. MDA dose-dependently induced micronuclei in hepatocytes in 14- and 28-day repeated-dose tests. However, although statistically significant increases in micronuclei were observed in bone marrow cells at two dose levels in the 14-day study, there was no dose response and no increases in micronuclei in the 28-day study. These results indicate that the evaluation of genotoxic effects using hepatocytes is effective in cases where chromosomal aberrations are not clearly detectable in bone marrow cells. Moreover, the repeated-dose liver MN test allows evaluation at a dose below the maximum tolerable dose, which is required for the conventional MN test because micronucleated hepatocytes accumulate. The repeated-dose liver MN test employed in the present study can be integrated into the spectrum of general toxicity tests without further procedural modifications.

  6. Neonatal Maternal Separation Augments Carotid Body Response to Hypoxia in Adult Males but Not Female Rats

    Science.gov (United States)

    Soliz, Jorge; Tam, Rose; Kinkead, Richard

    2016-01-01

    Perinatal exposure to adverse experiences disrupts brain development, including the brainstem network that regulates breathing. At adulthood, rats previously subjected to stress (in the form of neonatal maternal separation; NMS) display features reported in patients suffering from sleep disordered breathing, including an increased hypoxic ventilatory response and hypertension. This effect is also sex-specific (males only). Based on these observations, we hypothesized that NMS augments the carotid body's O2-chemosensitivity. Using an isolated and perfused ex vivo carotid body preparation from adult rats we compared carotid sinus nerve (CSN) responses to hypoxia and hypercapnia in carotid bodies harvested from adult rats that either experienced control conditions (no experimental manipulation) or were subjected to NMS (3 h/day from postnatal days 3 to 12). In males, the CSN response to hypoxia measured in preparations from NMS males was 1.5 fold higher than controls. In control rats, the female's response was similar to that of males; however, the increase in CSN activity measured in NMS females was 3.0 times lower than controls. The CSN response to hypercapnia was not influenced by stress or sex. We conclude that NMS is sufficient to have persistent and sex-specific effects on the carotid body's response to hypoxia. Because NMS also has sex-specific effects on the neuroendocrine response to stress, we propose that carotid body function is influenced by stress hormones. This, in turn, leads to a predisposition toward cardio-respiratory disorders. PMID:27729873

  7. Histological effects of oral administration of nutmeg on the kidneys of adult Wister rats

    Directory of Open Access Journals (Sweden)

    Andrew Osayame Eweka

    2010-01-01

    Full Text Available Aims: The effects of oral administration of nutmeg commonly used as spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the kidneys of adult Wistar rats were carefully studied. Material and Methods: Rats of both sexes (n = 24, with average weight of 220g were randomly assigned into two treatments (A & B of (n=16 and Control (c (n=8 groups. The rats in the treatment groups (A & B received 0.1g (500mg/kg body weight and 0.2g (1000mg/kg body weight of nutmeg thoroughly mixed with the feeds respectively on a daily basis for forty-two days. The control group (c received equal amount of feeds daily without nutmeg added for forty-two days. The growers′ mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state, Nigeria and the rats were given water liberally. The rats were sacrificed by cervical dislocation on the forty-third day of the experiment. The kidneys were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological study after hematoxylin and eosin method. Result: The histological findings in the treated sections of the kidneys showed distortion of the renal cortical structures, vacuolations appearing in the stroma and some degree of cellular necrosis, with degenerative and atrophic changes when compared to the control group. Conclusion: These findings indicate that oral administration of nutmeg may have some deleterious effects on the kidneys of adult Wistar rats at higher doses and by extension may affect its excretory and other metabolic functions. It is recommended that caution should therefore be advocated in the intake of this product and further studies be carried out to examine these findings.

  8. Histological effects of oral administration of nutmeg on the kidneys of adult Wister rats

    Directory of Open Access Journals (Sweden)

    Andrew Osayame Eweka

    2010-04-01

    Full Text Available Aims: The effects of oral administration of nutmeg commonly used as spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the kidneys of adult Wistar rats were carefully studied. Material and Methods: Rats of both sexes (n = 24, with average weight of 220g were randomly assigned into two treatments (A & B of (n=16 and Control (c (n=8 groups. The rats in the treatment groups (A & B received 0.1g (500mg/kg body weight and 0.2g (1000mg/kg body weight of nutmeg thoroughly mixed with the feeds respectively on a daily basis for forty-two days. The control group (c received equal amount of feeds daily without nutmeg added for forty-two days. The growers’ mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state, Nigeria and the rats were given water liberally. The rats were sacrificed by cervical dislocation on the forty-third day of the experiment. The kidneys were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological study after hematoxylin and eosin method. Result: The histological findings in the treated sections of the kidneys showed distortion of the renal cortical structures, vacuolations appearing in the stroma and some degree of cellular necrosis, with degenerative and atrophic changes when compared to the control group. Conclusion: These findings indicate that oral administration of nutmeg may have some deleterious effects on the kidneys of adult Wistar rats at higher doses and by extension may affect its excretory and other metabolic functions. It is recommended that caution should therefore be advocated in the intake of this product and further studies be carried out to examine these findings.

  9. Neuroprotective potential of phytochemicals

    Directory of Open Access Journals (Sweden)

    G Phani Kumar

    2012-01-01

    Full Text Available Cognitive dysfunction is a major health problem in the 21st century, and many neuropsychiatric disorders and neurodegenerative disorders, such as schizophrenia, depression, Alzheimer′s Disease dementia, cerebrovascular impairment, seizure disorders, head injury and Parkinsonism, can be severly functionally debilitating in nature. In course of time, a number of neurotransmitters and signaling molecules have been identified which have been considered as therapeutic targets. Conventional as well newer molecules have been tried against these targets. Phytochemicals from medicinal plants play a vital role in maintaining the brain′s chemical balance by influencing the function of receptors for the major inhibitory neurotransmitters. In traditional practice of medicine, several plants have been reported to treat cognitive disorders. In this review paper, we attempt to throw some light on the use of medicinal herbs to treat cognitive disorders. In this review, we briefly deal with some medicinal herbs focusing on their neuroprotective active phytochemical substances like fatty acids, phenols, alkaloids, flavonoids, saponins, terpenes etc. The resistance of neurons to various stressors by activating specific signal transduction pathways and transcription factors are also discussed. It was observed in the review that a number of herbal medicines used in Ayurvedic practices as well Chinese medicines contain multiple compounds and phytochemicals that may have a neuroprotective effect which may prove beneficial in different neuropsychiatric and neurodegenerative disorders. Though the presence of receptors or transporters for polyphenols or other phytochemicals of the herbal preparations, in brain tissues remains to be ascertained, compounds with multiple targets appear as a potential and promising class of therapeutics for the treatment of diseases with a multifactorial etiology.

  10. Neuroprotective Effect of Portulaca oleraceae Ethanolic Extract Ameliorates Methylmercury Induced Cognitive Dysfunction and Oxidative Stress in Cerebellum and Cortex of Rat Brain.

    Science.gov (United States)

    Sumathi, Thangarajan; Christinal, Johnson

    2016-07-01

    Methylmercury (MeHg) is highly toxic, and its principal target tissue in human is the nervous system, which has made MeHg intoxication a public health concern for many decades. Portulaca oleraceae (purslane), a member of the Portulacaceae family, is widespread as a weed and has been ranked the eighth most common plant in the world. In this study, we sought for potential beneficial effects of Portulaca oleracea ethanolic extract (POEE) against the neurotoxicity induced by MeHg in cerebellum and cortex of rats. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with POEE (4 mg/kg, orally) 1 h prior to the administration of MeHg for 21 days. After MeHg exposure, we determine the mercury concentration by atomic absorption spectroscopy (AAS); mercury content was observed high in MeHg-induced group. POEE reduced the mercury content. We also observed that the activities of catalase, superoxide dismutase, glutathione peroxidase, and the level of glutathione were reduced. The levels of glutathione reductase and thiobarbituric acid reactive substance were found to be increased. The above biochemical changes were found to be reversed with POEE. Behavioral changes like decrease tail flick response, longer immobility time, and decreased motor activity were noted down during MeHg exposure. POEE pretreatment offered protection from these behavioral changes. MeHg intoxication also caused histopathological changes in cerebellum and cortex, which was found to be normalized by treatment with POEE. The present results indicate that POEE has protective effect against MeHg-induced neurotoxicity.

  11. Role of the Toll‑like receptor 3 signaling pathway in the neuroprotective effect of sevoflurane pre‑conditioning during cardiopulmonary bypass in rats.

    Science.gov (United States)

    Zhou, Jin; Zhou, Nan; Wu, Xiao-Ning; Cao, Hui-Juan; Sun, Ying-Jie; Zhang, Tie-Zheng; Chen, Ke-Yan; Yu, Dong-Mei

    2015-12-01

    The aim of the present study was to explore the roles and possible molecular mechanism of the alleviating effect of sevoflurane pre‑treatment on the extracorporeal circulation and to investigate the possible involvement of the Toll‑like receptor (TLR3) signaling pathway. A total of 64 male Sprague Dawley rats were randomly divided into three groups: The sham operation group (H group; n=8), cardiopulmonary bypass (CPB) group (C group; n=24) and sevoflurane pre‑conditioning group (S group; n=32). The C group was subjected to tracheal intubation and mechanical ventilation, vessel puncture and catheter placement in the right femoral artery and right internal jugular vein, while no CPB was performed in the H group. The S group was pre‑treated with 2.4% sevoflurane for 1 h prior to establishing the CPB model. The CPB in the C and S groups was performed for 1 h. Blood of the rats was analyzed and clinical parameters were detected prior to, during and at various time‑points after CPB. In addition, eight rats from the C and S groups each were sacrificed at these time‑points and brain tissue samples were analyzed. The levels of the brain damage‑specific protein S100‑β as well as IL‑6 and IFN‑β in the serum were detected by ELISA; furthermore, the expression levels of TLR3 and TIR‑domain‑containing adapter‑inducing interferon‑β (TRIF) in the left hippocampus were assessed by ELISA and/or western blot analysis. The right hippocampus was assessed for neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The mean arterial pressure, heart rate and hematocrit were significantly decreased following CPB (Psevoflurane‑pre‑treatment. Compared with the H group, the serum levels of IFN‑β as well as hippocampal protein levels of TLR3 and TRIF were significantly increased in the C group during and after CPB (Psevoflurane‑pre‑treatment (Psevoflurane pre‑treatment has a protective effect on the rat brain

  12. Caffeine in the neonatal period induces long-lasting changes in sleep and breathing in adult rats.

    Science.gov (United States)

    Montandon, Gaspard; Horner, Richard L; Kinkead, Richard; Bairam, Aida

    2009-11-15

    Caffeine is commonly used clinically to treat apnoeas and unstable breathing associated with premature birth. Caffeine antagonizes adenosine receptors and acts as an efficient respiratory stimulant in neonates. Owing to its persistent effects on adenosine receptor expression in the brain, neonatal caffeine administration also has significant effects on maturation of the respiratory control system. However, since adenosine receptors are critically involved in sleep regulation, and sleep also modulates breathing, we tested the hypothesis that neonatal caffeine treatment disrupts regulation of sleep and breathing in the adult rat. Neonatal caffeine treatment (15 mg kg(-1) day(-1)) was administered from postnatal days 3-12. At adulthood (8-10 weeks old), sleep and breathing were measured with a telemetry system and whole-body plethysmography respectively. In adult rats treated with caffeine during the neonatal period, sleep time was reduced, sleep onset latency was increased, and non-rapid eye movement (non-REM) sleep was fragmented compared to controls. Ventilation at rest was higher in caffeine-treated adult rats compared to controls across sleep/wake states. Hypercapnic ventilatory responses were significantly reduced in caffeine-treated rats compared to control rats across sleep/wake states. Additional experiments in adult anaesthetized rats showed that at similar levels of arterial blood gases, phrenic nerve activity was enhanced in caffeine-treated rats. This study demonstrates that administration of caffeine in the neonatal period alters respiratory control system activity in awake and sleeping rats, as well as in the anaesthetized rats, and also has persistent disrupting effects on sleep that are apparent in adult rats.

  13. Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

    Science.gov (United States)

    Greco, Tiffany; Hovda, David A; Prins, Mayumi L

    2015-02-01

    Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults.

  14. Superior neuroprotective effects of cerebrolysin in nanoparticle-induced exacerbation of hyperthermia-induced brain pathology.

    Science.gov (United States)

    Sharma, Aruna; Muresanu, Dafin Fior; Mössler, Herbert; Sharma, Hari Shanker

    2012-02-01

    In recent years, the incidence of heat stroke and associated brain pathology are increasing Worldwide. More than half of the world's population are living in areas associated with high environmental heat especially during the summer seasons. Thus, new research is needed using novel drug targets to achieve neuroprotection in heat-induced brain pathology. Previous research from our laboratory showed that the pathophysiology of brain injuries following heat stroke are exacerbated by chronic intoxication of engineered nanoparticles of small sizes (50-60 nm) following identical heat exposure in rats. Interestingly, in nanoparticle-intoxicated animals the known neuroprotective agents in standard doses failed to induce effective neuroprotection. This suggests that the dose-response of the drugs either requires modification or new therapeutic agents are needed to provide better neuroprotection in nanoparticle-intoxicated animals after heat stroke. This review is focused on the use of cerebrolysin, a mixture of several neurotrophic factors and active peptide fragments, in relation to other neuroprotective agents normally used to treat ischemic stroke in clinics in nanoparticle-induced exacerbation of brain damage in heat stroke. It appears that cerebrolysin exerts the most superior neuroprotective effects in heat stress as compared to other neuroprotective agents on brain pathology in normal rats. Interestingly, to induce effective neuroprotection in nanoparticle-induced exacerbation of brain pathology a double dose of cerebrolysin is needed. On the other hand, double doses of the other drugs were quite ineffective in reducing brain damage. These observations suggest that the drug type and doses are important factors in attenuating nanoparticle-induced exacerbation of brain pathology in heat stroke. The functional significance and possible mechanisms of drug-induced neuroprotection in nanoparticle-treated, heat-stressed rats are discussed.

  15. The time course of denervation-induced changes is similar in soleus muscles of adult and old rats.

    NARCIS (Netherlands)

    Degens, H.; Kosar, S.N.; Hopman, M.T.E.; Haan, A. de

    2008-01-01

    Muscle denervation is accompanied by atrophy and a decline in oxidative capacity. We investigated whether the time course of adaptations following denervation of the soleus muscle differs in adult (5 months old) and older adult (25 months old) rats. We denervated the soleus muscle of the left leg, w

  16. A SELF-PRIMING EFFECT OF LHRH ON LH SECRETION IN DISPERSED ANTERIOR PITUITARY CELLS OF ADULT MALE RAT

    Institute of Scientific and Technical Information of China (English)

    QUZhi-Chao; GUOJing; GUOJian

    1989-01-01

    LHRH self-priming effect is simply defmed as an enhancement of LH response to LHRH, i. e., a second challenge with LHRH elicits more LH secretion as compared to the first challenge. The present study is to observe whether this phenomenon exists in perfused anterior pituitary (AP) cells of adult male rat. Dispersed AP cells of adult SD

  17. ZP2307, a novel cyclic PTH(1-17) analog, reversed established osteopenia in adult ovariectomized rats

    DEFF Research Database (Denmark)

    Vääräniemi, Jukka; Morko, Jukka; Peng, ZhiQi

    -17) analog, ZP2307, with a high efficacy and potency on the human PTH receptor in vitro. This study characterized the effects of intermittent treatment with ZP2307 on established osteopenia in adult ovariectomized (OVX) rats. Female Sprague-Dawley rats were ovariectomized at 6 months of age. After 6 weeks......-34). This study demonstrated that the intermittent treatment with ZP2307, the novel cyclic PTH(1-17) analog, is effective in reversing the established osteopenia in adult OVX rats to normal conditions. Due to its broad dose response relationship, ZP2307 may have a wider therapeutic window and a better safety...

  18. Effect of glial cell line-derived neurotrophic factor on peripheral nerve regeneration in adult rat

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhe-yu; LI Jian-hong; ZHENG Xing-dong; LU Chang-lin; HE Cheng

    2001-01-01

    Objective: To study the effect of glial cell line-derived neurotrophic (GDNF) on adult peripheral nerve regeneration. Methods: Transectioned sciatic nerve in adult rats was sutured into silicone channel. GDNF or SAL solution was injected into the silicone channels during operation. Four weeks later, the effect of GDNF on axonal regeneration was evaluated by degenerative neurofiber staining and HRP retrograde tracing. Results: Compared with SAL group, the percentage of degenerative neurofiber areas decreased from 17.3% to 1.9% ( P<0.01 ) and the ratio of labeled spinal somas number was significantly increased from 43.5% to 68.3% ( P<0.01 ) in GDNF group. Conclusion: The results suggest that exogenous GDNF can obviously enhance adult peripheral nerve regeneration.

  19. Effects of Infantile Repeated Hyperglycemia on Behavioral Alterations in Adult Rats

    Directory of Open Access Journals (Sweden)

    Malihe Moghadami

    2012-09-01

    Full Text Available Anxiety symptoms have been reported to be present in many patients with diabetes mellitus. However, little is known about the effects of hyperglycemia in critical periods of the central nervous system development. We assessed locomotive, exploratory, and anxiety behaviors in adult rats that remained from infantile repeated hyperglycemia by the open field and elevated plus maze tests. Our findings showed significant hypo activity, reduced locomotive/exploratory activities, increased fear related behaviors, and anxiety state between hyperglycemic and control adult males and the same differences were observed among females. In addition, no significant behavioral alterations between male and female animals were observed. This study determined that repeated increments in daily blood sugar levels in newborns may affect neuronal functions and provide behavioral abnormalities in adults.

  20. Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat

    DEFF Research Database (Denmark)

    Madsen, Torsten Meldgaard; Kristjansen, P.E.G.; Bolwig, Tom Gert

    2003-01-01

    The generation of new neurons in the adult mammalian brain has been documented in numerous recent reports. Studies undertaken so far indicate that adult hippocampal neurogenesis is related in a number of ways to hippocampal function.Here, we report that subjecting adult rats to fractionated brain...... days after irradiation, the animals with blocked neurogenesis performed poorer than controls in a hippocampus-dependent place-recognition task, indicating that the presence of newly generated neurons may be necessary for the normal function of this brain area. The animals were never impaired...... irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At different time points after the termination of the irradiation procedure, the animals were tested in two tests of short-term memory that differ with respect to their dependence on hippocampal function. Eight and 21...

  1. Effect of maternal obesity on diabetes development in adult rat offspring.

    Science.gov (United States)

    de Campos, Kleber Eduardo; Sinzato, Yuri Karen; Pimenta, Walkyria de Paula; Rudge, Marilza Vieira Cunha; Damasceno, Débora Cristina

    2007-10-27

    This study aimed to evaluate whether maternal obesity leads to the onset of diabetes in adult Wistar rats offspring. MSG solution neonatally administration induced obesity in rats (F(1)MSG group, n=30); and saline solution was also administrated to control rats (F(1)CON group, n=13). In 3rd month of age, both control and MSG groups were mated for offspring (generation F(2)), named as F(2)CON, n=28 and F(2)MSG groups, n=15; and so both generations were studied until 7th month of life. Lee Index was measured for experimental obesity validation from 5th to 7th month. Glycemia was weekly determined during pregnancy and monthly from 3rd to 7th month. In the end of experimental period all rats were submitted to oral glucose tolerance test (OGTT), with estimation of total area under the curve (AUC); and insulin tolerance test (ITT). Rats were then anesthetized and killed. Data were statistically analyzed with significance level of pgenerations showed significant maternal interference in control and MSG groups. OGTT analysis showed higher glycemia in obese rats (F(1)MSG) and their offspring (F(2)MSG) as compared to their respective controls; and MSG groups increased AUC from OGTT. As regards ITT, F(2)MSG showed higher glycemia at 30 and 120 min, suggesting a delay of insulin action decreasing. Although glucose intolerance and insulin resistance clinical conditions represent as a factors for type 2 Diabetes mellitus development, this experimental model proposal was not efficient to induce type 2 Diabetes mellitus, but for obesity developing, glucose intolerance and insulin resistance in successive generations of rats.

  2. Alterations in cytochrome P-450 levels in adult rats following neonatal exposure to xenobiotics

    Energy Technology Data Exchange (ETDEWEB)

    Zangar, R.C. (Oregon State Univ., Corvallis (United States) Pacific Northwest Laboratories, Richland, WA (United States)); Springer, D.L. (Pacific Northwest Laboratories, Richland, WA (United States)); Buhler, D.R. (Oregon State Univ., Corvallis (United States))

    1993-01-01

    Neonatal exposure to certain xenobiotics has been shown to alter hepatic metabolism in adult rats in a manner that indicates long-term changes in enzyme regulation. Previously, the authors have observed changes in adult testosterone metabolism and in cytochrome P-450 (P-450) mRNA levels in animals neonatally exposed to phenobarbital (PB) or diethylstilbestrol (DES). In order to test for other enzyme alterations, they used Western blot procedures for specific P-450s to analyze hepatic microsomes from adult rats (24 wk old) that had been exposed neonatally to DES, PB, 7,12-dimethylbenz[a]anthracene (DMBA), or pregnenolone 16[alpha]-carbonitrile (PCN). The most striking effects were observed in the DES-treated males: P-4502C6 and an immunologically similar protein were increased 60 and 90%, respectively, relative to control values, but P-4503A2 was decreased by 44%. No changes were observed in the DES-treated males in levels of P-4502E1, P-4502B, or the male-specific P-4502C13. Adult males neonatally treated with PB had 150% increase in levels of anti-P4502B-reactive protein without significant changes in the other enzymes. The DES- and DMBA-treated females had increased levels of the female-specific P-4502C12 of 38 and 48%, respectively, but no other observed alterations. The results confirm that neonatal exposure to DES or PB can cause alterations in adult hepatic cytochrome P-450 levels but show that these chemicals act on different enzymes. Neonatal DMBA resulted in changes in adult females similar to those produced by the synthetic estrogen DES, but did so at about two-thirds lower dose. 37 refs., 5 figs.

  3. Neuroprotective effect of melatonin on preterm rat after hypoxia-ischemia brain damage%褪黑素对新生大鼠缺血缺氧后脑损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    乔丽丽; 沈伟勤; 陈国宏

    2012-01-01

    目的 探讨褪黑素对新生大鼠缺氧缺血性脑损伤 (HIBD) 的保护作用.方法 Wistar大鼠 48 只,5日龄时结扎左侧颈总动脉,吸入氧氮混合气体 50 min 制作成HIBD模型,随机分成生理盐水组,褪黑素组,缺血缺氧 (HI)+生理盐水组,HI+褪黑素组.褪黑素腹腔注射共 3 次,每次 5 mg/kg,第 1 次在结扎动脉前,第 2 次在吸入氧氮混合气体前给予,第 3 次在HIBD模型制作 24 h 后给予.大鼠在HIBD模型制作后 72 h 被处死,取脑作免疫组化染色,判断脑灰质 (microtubule-associatedprotein-2,MAP-2)、脑白质 (myelin basic protein,MBP) 损伤;HIBD模型制作后 7 周作Y迷宫记忆功能测试.结果 褪黑素能明显减轻HIBD大鼠脑灰质MAP-2和脑白质MBP损伤,还可提高大鼠的长期记忆能力和运动协调能力.结论 褪黑素对HIBD大鼠大脑损伤有明显的短期和长期保护作用.%Objective To investigate neuroprotective effect of melatonin on newborn rat brain after hypoxia-ischemia brain damage (HIBD). Methods Forty-eight 5-day-old Wistar rats were randomly divided into physiological saline group, melatonin group, hypoxia-ischemia (HI) + saline group and HI + melatonin group. The HIBD rat models were induced by unilateral ligation of the left common carotid artery followed by 50 min inhalation of mixed oxygen and nitrogen. Melatonin was intraperitoneally injected three times with a dose of 5mg/kg before artery ligation, before ischemia and after 24h HI immediately. The rats were sacrified after 72h HI and the immunohistochemical staining was applied to brain tissue. Microtubule-associated protein-2 (MAP-2) and myelin basic protein (MBP) were evaluated as indicators for damages in grey matter and white matter, respectively. The memory abilities of the rats were measured through Y maze test at 7 weeks after HI. Results Melatonin treatment reduced the injury of grey matter and white matter significantly, and improved the long-term memory ability and motor

  4. The neuroprotective effect of piperine on focal cerebral ischemia in rats%胡椒碱对大鼠局灶性脑缺血的神经保护作用

    Institute of Scientific and Technical Information of China (English)

    郑显东; 杨非; 宋怡诚; 孙家合; 李军

    2014-01-01

    Objective To investigate the neuroprotective effect of piperine on acute ischemic brain injury in rats.Methods Thirty-two SD rats were randomly divided into four groups,namely shamed group with saline,saline group with saline,vehicle group with vehicle and piperine group with piperine.The MCAO model was established with suture occlusion technique according to modified Zea Longa method.The neurologic impairments were evaluated at 2 h,24 h,48 h and 72 h after operation of MCAO.All of the rats were killed at 72 h.The infarct vol-umes were calculated by TTC staining.The other 32 male SD rats were treated the same as above.The rats were killed at 24 h after MCAO.The apoptosis cell and expression of caspase-3 were detected.Results The neurological deficit scores of piperine group were signifi -cantly decreased compared with saline and vehicle group.The piperine could reduce the infarcted volumesof the apoptosis cells and caspase-3 positive cells(P <0.05).Conclusion The piperine can decrease the infarcted volumes and inhibit the apoptosis of cells by reducing the ex-pression of caspase-3.%目的:观察胡椒碱对急性缺血性脑损伤大鼠的神经保护作用。方法随机将 SD 大鼠分为假手术组、生理盐水组、胡椒碱组、溶媒组,每组8只。采用颈内动脉线栓法制备大鼠大脑中动脉闭塞脑缺血模型,术后0.5 h 灌胃给药,1次/d,连续3 d。不同时间点进行神经功能评分。72 h 断头取脑,TTC 染色,测量梗死体积。另择32只大鼠,分组同上,于脑缺血24 h 处死,断头取脑,观察神经细胞凋亡及 Caspase-3蛋白表达。结果胡椒碱组大鼠神经功能评分、脑梗死体积、凋亡细胞数及 Caspase-3阳性细胞数较生理盐水组、胡椒碱溶媒组降低,差异有统计学意义(P <0.05)。结论胡椒碱通过减少 Caspase-3蛋白的表达抑制细胞凋亡、缩小脑梗死体积、改善神经功能。

  5. Environmental enrichment potentiates thalamocortical transmission and plasticity in the adult rat visual cortex.

    Science.gov (United States)

    Mainardi, Marco; Landi, Silvia; Gianfranceschi, Laura; Baldini, Sara; De Pasquale, Roberto; Berardi, Nicoletta; Maffei, Lamberto; Caleo, Matteo

    2010-11-01

    It has been demonstrated that the complex sensorimotor and social stimulation achieved by rearing animals in an enriched environment (EE) can reinstate juvenile-like plasticity in the adult cortex. However, it is not known whether EE can affect thalamocortical transmission. Here, we recorded in vivo field potentials from the visual cortex evoked by electrical stimulation of the dorsal lateral geniculate nucleus (dLGN) in anesthetized rats. We found that a period of EE during adulthood shifted the input-output curves and increased paired-pulse depression, suggesting an enhanced synaptic strength at thalamocortical terminals. Accordingly, EE animals showed an increased expression of the vesicular glutamate transporter 2 (vGluT-2) in geniculocortical afferents to layer IV. Rats reared in EE also showed an enhancement of thalamocortical long-term potentiation (LTP) triggered by theta-burst stimulation (TBS) of the dLGN. To monitor the functional consequences of increased LTP in EE rats, we recorded visual evoked potentials (VEPs) before and after application of TBS to the geniculocortical pathway. We found that responses to visual stimulation were enhanced across a range of contrasts in EE animals. This was accompanied by an up-regulation of the intracortical excitatory synaptic marker vGluT-1 and a decrease in the expression of the vesicular GABA transporter (vGAT), indicating a shift in the excitation/inhibition ratio. Thus, in the adult rat, EE enhances synaptic strength and plasticity of the thalamocortical pathway associated with specific changes in glutamatergic and GABAergic neurotransmission. These data provide novel insights into the mechanisms by which EE shapes the adult brain.

  6. Distinct Testicular Steroidogenic Response Mechanisms Between Neonatal and Adult Heat-Acclimated Male Rats

    Directory of Open Access Journals (Sweden)

    Beata Kurowicka

    2015-03-01

    Full Text Available Background: In comparison to short-term gonad heat exposure, little is known about the molecular mechanisms that regulate testicular steroidogenesis during long-term whole body heat acclimation. Material and Methods: Testicular slices from neonatal (NHA and adult (AHA heat-acclimated Wistar rats were analysed in vitro to assess the mRNA expression and enzymatic activity of steroidogenic enzymes under basal and luteinising hormone (LH or prolactin (PRL stimulated conditions compared with control rats (CR. Furthermore, a de-acclimated group (DA was created by transferring adult NHA rats to control conditions. Results: Heat acclimation significantly increased plasma LH levels in the AHA group and LH and PRL in the NHA group compared with the CR group; however, after heat acclimation, the T and E2 levels did not differ from the control levels. All heat-acclimated groups showed high basal intra-testicular steroid production in vitro. Moreover, basal Cyp11a1 and Hsd3b1 levels were upregulated in vitro in the NHA and DA groups versus the CR group. LH in vitro stimulation upregulated Cyp11a1 expression in the NHA and AHA groups and PRL stimulation upregulated Cyp17a1 levels in the NHA and DA groups compared with the basal expression levels. In the AHA group, decreased basal Star and CYP11A activities but increased HSD3B1 and CYP17A1 activities were found. Conclusion: Our data revealed that despite the similar steroid levels in plasma and secreted in vitro by neonatal and adult heat-acclimated rat testicular slices, the molecular mechanisms underlying the steroidogenic response to heat acclimation during these different developmental stages were distinct.

  7. Impact of chronic nicotine administration on bone mineral content in young and adult rats: a comparative study.

    Science.gov (United States)

    Farag, Mahmoud M; Selima, Eman A; Salama, Mona A

    2013-11-15

    The aim of this study was to evaluate the effects of chronic nicotine administration on bone mineral homeostasis in rapidly growing young rats in comparison to effects in adult male rats. Two doses of nicotine (3 and 4.5mg/kg/day, as nicotine hydrogen tartrate) were used and rat treatment was continued for 6 months. In this study, all nicotine-treated rats weighed less than control rats and the effect was dose-dependent. Also, rats treated with nicotine had lower femoral wet weight and showed a significant reduction in femoral mid-shaft cortical width and femoral and lumbar vertebral ash weights. These effects were associated with a significant reduction of ash calcium and phosphorus contents of the femora and lumbar vertebrae. The bone mineral-lowering effects of nicotine were more severe in the lumbar vertebral spongy bone than in the femoral compact bone and these changes were more marked in adult rats than in young rats. An additional interesting observation was that the femora of young rats treated with nicotine were significantly shorter than those of control young rats. Also, the values of the femoral ash weight per unit length were significantly decreased in nicotine-treated adult rats but not in nicotine-treated young rats. Thus, these results show that nicotine-induced changes in bone vary with age. The clinical relevance of this study is that it may provide justification to insist that all people in general and the risky young group in particular should be warned against the hazards of the negative effects of nicotine on bone.

  8. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity.

    Science.gov (United States)

    van de Heijning, Bert J M; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M

    2015-07-08

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%-75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.

  9. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity

    Directory of Open Access Journals (Sweden)

    Bert J. M. van de Heijning

    2015-07-01

    Full Text Available Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control. A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.

  10. Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats.

    Science.gov (United States)

    Spritzer, M D; Curtis, M G; DeLoach, J P; Maher, J; Shulman, L M

    2016-03-24

    Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of 5-bromo-2'-deoxyuridine (BrdU) (200mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30-min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohistochemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. Males in the familiar group engaged in significantly more sexual behavior (ejaculations and intromissions) than did males in the unfamiliar group, suggesting that level of sexual activity may influence neurogenesis levels. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect is stronger for sexual

  11. 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.

  12. Neuroprotective-Neurotrophic Effect of Endogenous Dehydroepiandrosterone Sulfate During Intense Stress Exposure

    Science.gov (United States)

    2014-06-02

    and neurogenesis [20]. Regarding neuroprotection, DHEA(S) is thought to exert pro-survival effects by modulating gamma-ami- nobutyric acid [18...Experimental evidence does suggest that DHEA(S) treatment yields neurogenesis [20] and neuroprotection [18], as well as NGF overproduction in brain cortex [27...J. Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the hippocampus of the rat, promotes survival of newly formed neurons and prevents

  13. BDNF Mediates Neuroprotection against Oxygen-Glucose Deprivation by the Cardiac Glycoside Oleandrin

    OpenAIRE

    Van Kanegan, Michael J.; He, Dong Ning; Dunn, Denise E.; Yang, Peiying; Newman, Robert A; West, Anne E.; Lo, Donald C.

    2014-01-01

    We have previously shown that the botanical drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, provides neuroprotection in both in vitro and in vivo brain slice-based models for focal ischemia (Dunn et al., 2011). Intriguingly, plasma levels of the neurotrophin BDNF were increased in patients treated with PBI-05204 in a phase I clinical trial (Bidyasar et al., 2009). We thus tested the hypothesis that neuroprotection provided by PBI-05204 to rat brain slices damaged by ...

  14. Neuroprotective Effects of Citicoline in in Vitro Models of Retinal Neurodegeneration

    OpenAIRE

    Andrea Matteucci; Monica Varano; Lucia Gaddini; Cinzia Mallozzi; Marika Villa; Flavia Pricci; Fiorella Malchiodi-Albedi

    2014-01-01

    In recent years, citicoline has been the object of remarkable interest as a possible neuroprotectant. The aim of this study was to investigate if citicoline affected cell survival in primary retinal cultures and if it exerted neuroprotective activity in conditions modeling retinal neurodegeneration. Primary retinal cultures, obtained from rat embryos, were first treated with increasing concentrations of citicoline (up to 1000 µM) and analyzed in terms of apoptosis and caspase activation and c...

  15. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

    Directory of Open Access Journals (Sweden)

    A. Zago

    2012-01-01

    Full Text Available Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P 28-37 and adult (P60-67 rats received nicotine (0.4 mg/kg, sc or saline (0.9% NaCl, sc and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

  16. 组蛋白去乙酰化酶抑制剂MS-275对创伤性脑损伤大鼠的神经保护作用%Neuroprotective effect of histone deacetylases inhibitor MS-275 following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    曹鹏; 宋振全; 于春泳; 冯思哲; 胡国汉; 卢亦成

    2013-01-01

    目的 探讨组蛋白去乙酰化酶(histone deacetylases,HDAC)抑制剂MS-275对大鼠中度创伤性颅脑损伤(traumatic brain injury,TBI)的神经保护作用. 方法 68只SD成年雄性大鼠按随机数字表法分为4组:无损伤对照+安慰剂组(对照组)、脑损伤+安慰剂组(损伤组)、脑损伤+ 15mg/kg MS-275组(治疗Ⅰ组)和脑损伤+45mg/kg MS-275组(治疗Ⅱ组).大鼠侧方液压打击装置诱导形成中度实验性TBI模型.MS-275溶解于二甲基亚砜中,15,45 mg/kg两种浓度的MS-275伤后连续7d(1次/d)腹腔注射大鼠体内,首次给药于伤后30 min完成.伤后记录各组大鼠体重变化,伤后10 ~ 14 d行Morris水迷宫测试评估大鼠空间探索及记忆存储功能.脑组织经提取固定后通过免疫组化及甲酚紫组织染色方法比较不同组别海马CA2 ~3区乙酰化组蛋白H3水平和存活神经细胞数量的差异. 结果 与对照组比较,其余3组伤后前3d体重均显著下降(P<0.05),伤后4~5d体重逐渐增加至伤前基础体重水平,但各组间差异无统计学意义(F=0.149,P>0.05).行为学测试结果显示,与损伤组比较,两治疗组均可明显改善大鼠伤后认知行为表现(P<0.01).组织染色结果显示,两治疗组均可明显增加脑组织乙酰化组蛋白H3水平,与对照组比较差异无统计学意义;伤后14 d两治疗组均表现出脑组织海马CA2 ~3区神经细胞存活数量增加的趋势(P>0.05). 结论 MS-275可显著改善大鼠TBI后急性期乙酰化组蛋白水平及认知行为功能,同时改善TBI后的病理变化,对神经起到一定的保护作用.%Objective To evaluate the neuroprotective benefits of histone deacetylases (HDAC)inhibitor MS-275 in rats with moderate traumatic brain injury (TBI).Methods Sixty-eight adult male SD rats were assigned to sham injury + placebo treatment (control group),TBI + placebo treatment (injury group),TBI + MS-275 (15 mg/kg) treatment (treatment group Ⅰ) and TBI + MS-275 (45

  17. Application of Luxol Fast Blue staining in locating the corticospinal tract in adult rats

    Institute of Scientific and Technical Information of China (English)

    Su Liu; Guangyu Shen; Guangming Lü; Xiaosong Gu

    2006-01-01

    BACKGROUND: There are many methods for myelin staining,mordant,or the special reaction of osmic acid with lipoid is used according to different principles.The commonly used methods are classic Well staining ,classic lithium carbonate-haematine staining,fast green staining,silver staining ,etc.Luxol Fast Blue can brightly stain myelin sheath,and has certain specificity .The background can be very clean if there is proper differentiation,whereas Luxol Fast Blue is cheap and convenient to operate,thus it is an ideal staining reagent for routine myelin sheath.OBJECTIVE: To show the coricospinal tract of normal adult rats with Luxol Fast Blue shaining method.DESIGN:A repetitive measurement design.SETTINGS: Institute of Nuerobiology,Nantong University;Department of Rehabilitation Medicine,Affiliated Hospital of Nantong University.MATERIALS: Six healthy adult male SD rats of clean dergree,weighing averagely 300 g.were provided by the experimental animal center of Nantong University.1 g/L Luxol Fast Blue solution was provided by Sigma Company;Leica CM1900 cryostat microtome by Leica Company;Leica DMR microscope by Leica Company.METHODS:The experiment was carried out in the Staff Room of Human Anatomy,Nantong University in May 2005.The rats were given intraperitoneal injection of combined anesthetic(2 mL/kg),then the chest was open for perfusing saline and phosphate buffer containing formamint via heart. Brain and spinal cord were removed after 1 hour then fixed,then changed to phosphate buffer(pH 7.4)containing 300 g/L saccharu at 4 ℃.and stayed overnight,tissue blocks at pyramid,decussation of pyramid and cervical,thoracic,lumbar and sacral segments of spinal cord were removed to prepare continuous horizontal frozen sections(30 μm) after sedimentation,the sections were dried at room temperature.The corticospinal tract of normal adult rats were shown with Luxol Fast Blue staining method,and observed under Leica DMR microscope.MAIN OUTCOME MEASURES:Positive fibers in

  18. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    Energy Technology Data Exchange (ETDEWEB)

    Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  19. Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition.

    Science.gov (United States)

    Engler-Chiurazzi, Elizabeth B; Stapleton, Phoebe A; Stalnaker, Jessica J; Ren, Xuefang; Hu, Heng; Nurkiewicz, Timothy R; McBride, Carroll R; Yi, Jinghai; Engels, Kevin; Simpkins, James W

    2016-01-01

    It is generally accepted that gestational xenobiotic exposures result in systemic consequences in the adult F1 generation. However, data on detailed behavioral and cognitive consequences remain limited. Using our whole-body nanoparticle inhalation facility, pregnant Sprague-Dawley rats (gestational day [GD] 7) were exposed 4 d/wk to either filtered air (control) or nano-titanium dioxide aerosols (nano-TiO2; count median aerodynamic diameter of 170.9 ± 6.4 nm, 10.4 ± 0.4 mg/m(3), 5 h/d) for 7.8 ± 0.5 d of the remaining gestational period. All rats received their final exposure on GD 20 prior to delivery. The calculated daily maternal deposition was 13.9 ± 0.5 µg. Subsequently, at 5 mo of age, behavior and cognitive functions of these pups were evaluated employing a standard battery of locomotion, learning, and anxiety tests. These assessments revealed significant working impairments, especially under maximal mnemonic challenge, and possible deficits in initial motivation in male F1 adults. Evidence indicates that maternal engineered nanomaterial exposure during gestation produces psychological deficits that persist into adulthood in male rats.

  20. Effect of pinealectomy, adrenalectomy, pinealectomy plus adrenalectomy upon the quantification of spermatogenic cells of adult rats

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    Castro A.C.S.

    2002-01-01

    Full Text Available The objectives of this study were to evaluate the effects of pinealectomy, adrenalectomy and pinealectomy-adrenalectomy upon the quantification of spermatogenic cells of rats. As such, 32 adult Wistar rats with a mean body weight of 331.7± 15.5g were assigned into one of the following treatments: (a a sham-operated control group, consisting of nine animals; (b ten pinealectomized animals; (c seven adrenalectomized animals and (d six pinealectomized plus adrenalectomized animals. No significant differences were observed between groups for the following parameters: body, testes, prostate and seminal vesicle weights, seminiferous tubular diameter, number of cells per seminiferous tubular cross sections (primary spermatocytes at pachytene, round spermatids, Sertoli cells and numbers of germ cells per Sertoli cell (primary spermatocytes at pachytene and round spermatids . Although no increase in testicular weight was observed following pinealectomy, a significant (P<0.05 increase of approximately 11.5% in the number of round spermatids per Sertoli cell (Sertoli cell ratio occurred thus suggesting that short-term pinealectomy abolishes the antigonadal effect of the pineal gland upon adult Wistar rat testes.

  1. Variability in the distribution of callosal projection neurons in the adult rat parietal cortex.

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    Ivy, G O; Gould, H J; Killackey, H P

    1984-07-23

    Previous reports have shown that the barrel field area of the parietal cortex of the adult rat contains relatively few callosal projection neurons, even though callosal projection neurons are abundant in this cortical region in the neonatal rat. Furthermore, it has been shown that many of the callosal neurons which seem to disappear as the animal matures do not die, but project to ipsilateral cortical areas. These findings rely on the ability of retrograde transport techniques which utilize injections of horseradish peroxidase (HRP) or of fluorescent dyes into one hemisphere. We now show that several technical modifications of the HRP technique yield a wider distribution of HRP-containing neurons in the contralateral barrel field area of the adult rat than previously reported. These include implants of HRP pellets into transected axons of the corpus callosum, the addition of DMSO and nonidet P40 to Sigma VI HRP, wheat germ agglutinin HRP and the use of tetramethyl benzidine as the chromogen in the reaction procedure. Our findings have implications for transport studies in general and for the development of the cortical barrel field in particular.

  2. Effects of moderate zinc deficiency on cognitive performance in young adult rats.

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    Massaro, T F; Mohs, M; Fosmire, G

    1982-07-01

    Two experiments were conducted to establish a dietary zinc level which approximates a moderate deficiency in the young adult rat and to determine if a concurrent zinc deficiency affects cognitive performance. Male rats were fed varying levels of zinc in diet throughout a 17-day period. The lowest dietary level that depressed serum and bone zinc without influencing food consumption or body weight gains was observed to be 5.8 microgram Zn/g diet. Young adult rats maintained on either a zinc adequate (24.4 microgram Zn/g) or low-zinc (5.3 microgram Zn/g) diet were tested in a modified Skinner Box involving tests of visual, auditory, association, and discrimination learning. No differences were observed in the visual discrimination performance of the zinc deficient animals when compared with control counterparts. Deficits in the ability to transfer a learned association between visual and auditory stimuli were observed, however, in the deficient group during the transfer test phase. The latter performed better during the final auditory discrimination task in transferring a learned food-relevant cue.

  3. Memantine对大鼠局灶性脑缺血损伤的长期神经保护效应%Long-term neuroprotective effects of memantine on focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    王枫; 雷翀; 邓姣; 桑韩飞; 马锐; 熊利泽

    2009-01-01

    AIM: To evaluate the long-term neuroprotective effects of memantine (MEM) on transient focal cerebral ischemic injury in rats. METHODS: Seventy male Spraque-Dawley rats were radomly divided into sham( n = 6), control( n = 16), MEM 5 (n =16), MEM 10(n = 16) and MEM 20(n = 16) groups. Each group except sham group were subjected to focal cerebral ischmia induced by middle cerebral artery occlusion (MCAO) for 2 h. MEM 5,MEM 10 and MEM 20 groups were administered intraperitoneally memantine 5,10 and 20 mg/kg respectively 15 min after focal cerebral ischemia. Control group were administered intraperitoneally normal saline of the same volume as memantine groups 15 rain after focal cerebral ischemia. After 7 d period of reperfusion, the animals were examined for neurological behavior scores and then killed to measure the infarct volumes and the content of TNFα and IL-6.RESULTS: The neurological behavior scores were better in MEM 10 and MEM 20 groups than those in control group, and the neurological score was better in MEM 20 group than that in MEM 10group, but no statistical difference was found between MEM 5 group and control group. The infarct volumes in MEM 10(27.06 ±6.6) % and MEM 20 groups( 21.32 ± I0.76 ) % were significantly smaller than those in control group( 41.3 ± 6.48 ) % ( P < 0.01 ) ,and the infarct volume in MEM 20 group significantly smaller than that in MEM 10 group( P <0.01 ), but no statistical difference was found between MEM 5 ( 35.98 ± 11.07 ) % and control group. The contents of TNFα and IL-6 were significantly increased in control group compared with those in sham group( P < 0.01 ). The cantents of TNFα and IL-6 were signafieantly decreased in MEM 10 group(5.72 ±0.60), ( 135.33 ±9.80) μg/L and MEM 20 group (5.28 ± 0.66), ( 123.67 ± 8.60) μg/L compared with those in control group( P < 0. 01 ). There is no statistical differences between MEM 5 group and control group. CONCLUSION: Memantine has long-term neuroprotective effects against

  4. Effects of long-term FK506 administration on functional and histopathological outcome after spinal cord injury in adult rat.

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    Saganová, Kamila; Orendácová, Judita; Sulla, Igor; Filipcík, Peter; Cízková, Dása; Vanický, Ivo

    2009-09-01

    FK506 (tacrolimus), a potent immunosuppressive drug primarily used for reduction of allograft rejection in organ transplantation, also offers neuroprotection after central nervous system injury. FK506-mediated immunosuppression and neuroprotection may occur through different mechanisms that could affect neurological recovery and the severity of spinal lesions where cells transplantation therapy is combined with FK506 application. We assessed effects of long-term FK506 administration using the same dose regiment (1 mg/kg/day for 6 weeks) as is used in spinal cord transplantation studies following a balloon-compression induced spinal cord injury (SCI). Body weight and locomotor recovery quantified by the BBB (Basso-Beattie-Bresnehan) locomotor rating scale were evaluated for up to 42 days post-injury. The area of the preserved spinal cord tissue within a 13 mm segment of the spinal cord (lesion epicenter and 6 mm rostral-caudal) was examined histologically. The results showed no significant effects of FK506 on spinal cord tissue sparing or improvement of locomotor recovery. However, body weight fell significantly (P < 0.05) with FK506 treatment when compared with placebo from day 7 until sacrifice. In our experimental design, long-term FK506 treatment did not affect the parameters of outcome following balloon-compression SCI in the rat; however, multiple effects of FK506 should be taken into account when evaluating the outcomes in transplantation studies.

  5. Early life stress enhancement of limbic epileptogenesis in adult rats: mechanistic insights.

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    Gaurav Kumar

    Full Text Available BACKGROUND: Exposure to early postnatal stress is known to hasten the progression of kindling epileptogenesis in adult rats. Despite the significance of this for understanding mesial temporal lobe epilepsy (MTLE and its associated psychopathology, research findings regarding underlying mechanisms are sparse. Of several possibilities, one important candidate mechanism is early life 'programming' of the hypothalamic-pituitary-adrenal (HPA axis by postnatal stress. Elevated corticosterone (CORT in turn has consequences for neurogenesis and cell death relevant to epileptogenesis. Here we tested the hypotheses that MS would augment seizure-related corticosterone (CORT release and enhance neuroplastic changes in the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: Eight-week old Wistar rats, previously exposed on postnatal days 2-14 to either maternal separation stress (MS or control brief early handling (EH, underwent rapid amygdala kindling. We measured seizure-induced serum CORT levels and post-kindling neurogenesis (using BrdU. Three weeks post-kindling, rats were euthanized for histology of the hippocampal CA3c region (pyramidal cell counts and dentate gyrus (DG (to count BrdU-labelled cells and measure mossy fibre sprouting. As in our previous studies, rats exposed to MS had accelerated kindling rates in adulthood. Female MS rats had heightened CORT responses during and after kindling (p<0.05, with a similar trend in males. In both sexes total CA3c pyramidal cell numbers were reduced in MS vs. EH rats post-kindling (p = 0.002. Dentate granule cell neurogenesis in female rats was significantly increased post-kindling in MS vs. EH rats. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that early life stress results in enduring enhancement of HPA axis responses to limbic seizures, with increased hippocampal CA3c cell loss and augmented neurogenesis, in a sex-dependent pattern. This implicates important candidate mechanisms through which early life

  6. Impaired contextual fear extinction and hippocampal synaptic plasticity in adult rats induced by prenatal morphine exposure.

    Science.gov (United States)

    Tan, Ji-Wei; Duan, Ting-Ting; Zhou, Qi-Xin; Ding, Ze-Yang; Jing, Liang; Cao, Jun; Wang, Li-Ping; Mao, Rong-Rong; Xu, Lin

    2015-07-01

    Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood.

  7. Protective effects of vitamin E and selenium on spermatogenesis in adult male rat insulin-resistant

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    Alireza Zakerabasali

    2013-03-01

    Full Text Available Background & Objective: Diabetes mellitus is a metabolic disease and is a multifactorial disorder characterized by chronic hyperglycemia resulting from impaired insulin secretion and insulin factional or both. In this study, the protective role of vitamin E and sodium selenite in preventing the harmful effects of insulin resistance (diabetes type 2 on spermatogenesis was studied.   Materials & Methods: Male adults (180-200 g of Wistar rats were divided into five groups, each containing 7 rats (control, sham, and three experimental groups. The rats were fed daily with water-soluble fructose (10%, mg/kg 200 of vitamin E (gavage, and 5/0 mg/kg of sodium selenite (intraperitoneal injection or both for 110 days. Subsequently, sperm parameters, levels of testosterone, LH, and daily sperm production (DSP were checked. Additionally, testicular histopathology and malondialdehyde (MDA in the testis were examined.   Results: Sperm count, sperm motility and viability, and insulin resistance in the rats decreased DSP. A significant decrease was observed in the number of Leydig cells, spermatogonia, spermatogenesis, and spermatozoa in the testis of the insulin-resistant animals, whereas MDA and testosterone rose in the insulin-resistant rats. Vitamin E and sodium selenite intake reduced the levels of MDA and harmful effects of fructose on testicles, as well as sperm parameters and testicular pathology. A simultaneous intake of vitamin E and sodium selenite conferred the highest level of protection.   Conclusion: These findings suggest that vitamin E and sodium selenite can have a protective role in the testes of rats against oxidative stress induced by diabetes type 2.

  8. Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats.

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    Galeano, Pablo; Romero, Juan Ignacio; Luque-Rojas, María Jesús; Suárez, Juan; Holubiec, Mariana Inés; Bisagno, Verónica; Santín, Luis Javier; De Fonseca, Fernando Rodríguez; Capani, Francisco; Blanco, Eduardo

    2013-09-01

    Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction.

  9. Ependymal cell proliferation and apoptosis following acute spinal cord injury in the adult rat

    Institute of Scientific and Technical Information of China (English)

    Xu Wang; Jun Qian; Yanchao Ma; Guoxin Nan; Shuanke Wang; Yayi Xia; Youcheng Zhang

    2008-01-01

    BACKGROUND: Studies have reported that spinal cord injury can induce the reactive proliferation of ependymal cells and secondarily cause the apoptosis of nerve cells. However, there is no generally accepted theory on the apoptotic characteristics of ependymal cells in the injured spinal cord.OBJECTIVE: To observe the reactive proliferation and apoptosis of ependymal cells in adult rats following acute spinal cord injury.DESIGN, TIME AND SETTING: A randomized control study based on neuropathology was performed in the Third Military Medical University of Chinese PLA between 2005 and 2007.MATERIALS: Forty healthy, adult, Wistar rats were included in the present study.METHODS: Moderate spinal cord injury was established in twenty rats using Feeney's method, while the remaining 20 rats served as controls and were only treated with laminectomy. All rats were injected intraperitoneally with 1.25 mL of BrdU solution (10 mg BrdU/mL saline) 3 times at 4 hours intervals during the 12 hours prior to sacrifice.MAIN OUTCOME MEASURES: Ependymal cell proliferation and apoptosis in the rat spinal cord were determined by BrdU and nestin immunofluorescence double-labeling, as well as the TUNEL method, at 1, 3, 7, and 14 days after operation.RESULTS: In the moderate spinal cord injury rats, nestin expression was observed in the cytoplasm of ependymal cells. One day immediately following surgery, ependymal cells were BrdU-labeled. The number of BrdU-positive cells increased at 3 days, reached a peak at 7 days, and gradually reduced thereafter. The ependyma developed ti'om a constitutive monolayer cells to a multi-layer cell complex. Some BrdU/Nestin double-positive ependymal cells migrated out from the ependyma. TUNEL-positive cells were also detected in the ependyma in the central region, as well as ischemic regions of the injured spinal cord. In addition, TUNEL-positive cells were visible in the ependyma. No TUNEL-positive ependymal cells were observed in the normal spinal cord

  10. Anti-Nogo-A Immunotherapy Does Not Alter Hippocampal Neurogenesis after Stroke in Adult Rats

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    Shepherd, Daniel J.; Tsai, Shih-Yen; O'Brien, Timothy E.; Farrer, Robert G.; Kartje, Gwendolyn L.

    2016-01-01

    Ischemic stroke is a leading cause of adult disability, including cognitive impairment. Our laboratory has previously shown that treatment with function-blocking antibodies against the neurite growth inhibitory protein Nogo-A promotes functional recovery after stroke in adult and aged rats, including enhancing spatial memory performance, for which the hippocampus is critically important. Since spatial memory has been linked to hippocampal neurogenesis, we investigated whether anti-Nogo-A treatment increases hippocampal neurogenesis after stroke. Adult rats were subject to permanent middle cerebral artery occlusion followed 1 week later by 2 weeks of antibody treatment. Cellular proliferation in the dentate gyrus was quantified at the end of treatment, and the number of newborn neurons was determined at 8 weeks post-stroke. Treatment with both anti-Nogo-A and control antibodies stimulated the accumulation of new microglia/macrophages in the dentate granule cell layer, but neither treatment increased cellular proliferation or the number of newborn neurons above stroke-only levels. These results suggest that anti-Nogo-A immunotherapy does not increase post-stroke hippocampal neurogenesis. PMID:27803646

  11. Neuroprotection by flavonoids

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    Dajas F.

    2003-01-01

    Full Text Available The high morbidity, high socioeconomic costs and lack of specific treatments are key factors that define the relevance of brain pathology for human health and the importance of research on neuronal protective agents. Epidemiological studies have shown beneficial effects of flavonoids on arteriosclerosis-related pathology in general and neurodegeneration in particular. Flavonoids can protect the brain by their ability to modulate intracellular signals promoting cellular survival. Quercetin and structurally related flavonoids (myricetin, fisetin, luteolin showed a marked cytoprotective capacity in in vitro experimental conditions in models of predominantly apoptotic death such as that induced by medium concentrations (200 µM of H2O2 added to PC12 cells in culture. Nevertheless, quercetin did not protect substantia nigra neurons in vivo from an oxidative insult (6-hydroxydopamine, probably due to difficulties in crossing the blood-brain barrier. On the other hand, treatment of permanent focal ischemia with a lecithin/quercetin preparation decreased lesion volume, showing that preparations that help to cross the blood-brain barrier may be critical for the expression of the effects of flavonoids on the brain. The hypothesis is advanced that a group of quercetin-related flavonoids could become lead molecules for the development of neuroprotective compounds with multitarget anti-ischemic effects.

  12. Microglia and neuroprotection.

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    Chen, Zhihong; Trapp, Bruce D

    2016-01-01

    Microglia were first identified over a century ago, but our knowledge about their ontogeny and functions has significantly expanded only recently. Microglia colonize the central nervous system (CNS) in utero and play essential roles in brain development. Once neural development is completed, microglia function as the resident innate immune cells of the CNS by surveying their microenvironment and becoming activated when the CNS is challenged by infection, injury, or disease. Despite the traditional view of microglia as being destructive in neurological diseases, recent studies have shown that microglia maintain CNS homeostasis and protect the CNS under various pathological conditions. Microglia can be prophylactically activated by modeling infection with systemic lipopolysaccharide injections and these activated microglia can protect the brain from traumatic injury through modulation of neuronal synapses. Microglia can also protect the CNS by promoting neurogenesis, clearing debris, and suppressing inflammation in diseases such as stroke, autism, and Alzheimer's. Microglia are the resident innate immune cells of the CNS. Despite the traditional view of microglia as being destructive in neurological diseases, recent studies have shown that they maintain tissue homeostasis and protect the CNS under various pathological conditions. They achieve so by clearing debris, promoting neurogenesis, suppressing inflammation and stripping inhibitory synapses. This review summarizes recent advances of our understanding on the multi-dimensional neuroprotective roles of microglia.

  13. Enriched Environment Protects the Optic Nerve from Early Diabetes-Induced Damage in Adult Rats.

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    Damián Dorfman

    Full Text Available Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Axoglial alterations of the distal (close to the chiasm optic nerve (ON could be the first structural change of the visual pathway in streptozotocin (STZ-induced diabetes in rats. We analyzed the effect of environmental enrichment on axoglial alterations of the ON provoked by experimental diabetes. For this purpose, three days after vehicle or STZ injection, animals were housed in enriched environment (EE or remained in a standard environment (SE for 6 weeks. Anterograde transport, retinal morphology, optic nerve axons (toluidine blue staining and phosphorylated neurofilament heavy immunoreactivity, microglia/macrophages (ionized calcium binding adaptor molecule 1 (Iba-1 immunoreactivity, astrocyte reactivity (glial fibrillary acid protein-immunostaining, myelin (myelin basic protein immunoreactivity, ultrastructure, and brain derived neurotrophic factor (BDNF levels were assessed in non-diabetic and diabetic animals housed in SE or EE. No differences in retinal morphology or retinal ganglion cell number were observed among groups. EE housing which did not affect the STZ-induced weight loss and hyperglycemia, prevented a decrease in the anterograde transport from the retina to the superior colliculus, ON axon number, and phosphorylated neurofilament heavy immunoreactivity. Moreover, EE housing prevented an increase in Iba-1 immunoreactivity, and astrocyte reactivity, as well as ultrastructural myelin alterations in the ON distal portion at early stages of diabetes. In addition, EE housing avoided a decrease in BDNF levels induced by experimental diabetes. These results suggest that EE induced neuroprotection in the diabetic visual pathway.

  14. Sodium metabisulfite-induced changes on testes, spermatogenesis and epididymal morphometric values in adult rats

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    Shahnaz Shekarforoush

    2015-12-01

    Full Text Available Background: Sulphites are widely used as a preservative and antioxidant additives in the food and pharmaceutical industries. Many types of biological and toxicological effects of sulphites in multiple organs of mammals have been shown in previous studies. Objective: The aim of this study was to investigate the effects of sodium metabisulfite (SMB on testicular function and morphometric values of epididymis in adult male Wistar rats. Materials and Methods: A total of 32 rats were randomly divided into four groups. The experimental groups received SMB at doses of 10 mg/kg (S10, 100mg/kg (S100, and 260 mg/kg (S260 while an equal volume of normal saline was administered to the control group via gavage. The rats were anaesthetized after 28 days and the left testis with the head of epididimis was excised following abdominal incision for histological observation using hematoxylin and eosin staining. Serum samples were collected for assay of testosterone level. The initial epididymis was analyzed for motility, morphology, and the number of sperms. Result: The results of this study showed that normal morphology, count, and motility of sperms and testosterone level were decreased in the SMB treated groups. In comparison with the control group, SMB resulted in a lower total number of spermatogonia, primary spermatocyte, spermatids, and Leydig cells. Conclusion: It is suggested that SMB decreases the sperm production and has the potential to affect the fertility adversely in male rats.

  15. Sugar overconsumption during adolescence selectively alters motivation and reward function in adult rats.

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    Leandro F Vendruscolo

    Full Text Available BACKGROUND: There has been a dramatic escalation in sugar intake in the last few decades, most strikingly observed in the adolescent population. Sugar overconsumption has been associated with several adverse health consequences, including obesity and diabetes. Very little is known, however, about the impact of sugar overconsumption on mental health in general, and on reward-related behavioral disorders in particular. This study examined in rats the effects of unlimited access to sucrose during adolescence on the motivation for natural and pharmacological rewards in adulthood. METHODOLOGY/PRINCIPAL FINDINGS: Adolescent rats had free access to 5% sucrose or water from postnatal day 30 to 46. The control group had access to water only. In adulthood, rats were tested for self-administration of saccharin (sweet, maltodextrin (non-sweet, and cocaine (a potent drug of abuse using fixed- and progressive-ratio schedules, and a concentration-response curve for each substance. Adult rats, exposed or not exposed to sucrose, were tested for saccharin self-administration later in life to verify the specificity of adolescence for the sugar effects. Sugar overconsumption during adolescence, but not during adulthood, reduced the subsequent motivation for saccharin and maltodextrin, but not cocaine. This selective decrease in motivation is more likely due to changes in brain reward processing than changes in gustatory perception. CONCLUSIONS/SIGNIFICANCE: Sugar overconsumption induces a developmental stage-specific chronic depression in reward processing that may contribute to an increase in the vulnerability to reward-related psychiatric disorders.

  16. Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study

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    Norman Ruthven Saunders

    2015-04-01

    Full Text Available The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analysed by functional groups of influx transporters, particularly solute carrier (SLC transporters. RNA-Seq was performed at embryonic day (E 15 and adult with additional data obtained at intermediate ages from microarray analysis. The largest represented functional group in the embryo was amino acid transporters (twelve with expression levels 2-98 times greater than in the adult. In contrast,