Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuronal damage following cerebral ischemia is mediated by various mechanisms, among which nitrosative stress plays an important role. Peroxynitrite, a powerful oxidant, contributes heavily to the neuronal damage in cerebral ischemic-reperfusion (IR) injury. In the present study, we have investigated the neuroprotective effects of a peroxynitrite decomposition catalyst, 5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrinato iron(III) [FeTPPS] in global cerebral IR injury in gerbils. Neurological damage was significantly attenuated by FeTPPS treatment (1 and 3mgkg(-1), i.p.) as evident from reduction in neurological symptoms, hyperlocomotion, memory impairment and CA1 hippocampal neuronal damage in IR challenged gerbils. FeTPPS treatment also attenuated the increased malondialdehyde (MDA) levels and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells after cerebral IR injury. Results of this study demonstrates the neuroprotective activity of FeTPPS in global cerebral IR injury and its neuroprotective effects may be attributed to reduction in oxidative stress and DNA fragmentation.
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PMID:FeTPPS protects against global cerebral ischemic-reperfusion injury in gerbils. 1729 20

Spatial cognitive impairment is common after stroke insults. Voluntary exercise could improve the impaired spatial memory. Newly generated neurons in the dentate gyrus are necessary for the acquisition of new hippocampus-dependent memories. However, it is not well known whether voluntary exercise after stroke promotes neurogenesis in the adult dentate gyrus, thereby promoting spatial memory recovery. Here, we examined in mice subjected to focal cerebral ischemia the effect of voluntary or forced exercise on neurogenesis in the ischemic dentate gyrus and spatial memory. Exposure to voluntary wheel running after stroke enhanced newborn cell survival and up-regulated the phosphorylation of cAMP response element binding protein (CREB) in the dentate gyrus and reversed ischemia-induced spatial memory impairment. However, the enhanced newborn cell survival and CREB phosphorylation in the dentate gyrus and improved spatial memory were not observed in the mice exposed to forced swimming. Moreover, there was a significant correlation between the total number of surviving newborn cells in the dentate gyrus and the ability of mice to locate the platform in the Morris water maze. These results suggest that, in the adult mice, exposure to voluntary exercise after ischemic stroke may promote newborn cells survival in the dentate gyrus by up-regulating CREB phosphorylation and consequently restore impaired hippocampus-dependent memory.
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PMID:Voluntary exercise-induced neurogenesis in the postischemic dentate gyrus is associated with spatial memory recovery from stroke. 1746 31

Recently, we have reported that quetiapine, an atypical antipsychotic drug, prevents memory impairment and hippocampus neurodegeneration induced by global cerebral ischemia (GCI). In the present study, we examined the possible effects of quetiapine on other behavioural deficits, including the depressive and anxiolytic-like behavioural consequences of GCI. Mice were treated with quetiapine (5 or 10mg/kg/day; intraperitoneal (i.p.)) for 14 days. On Day 15, the animals were subjected to GCI. GCI resulted in a decrease of striatal tyrosine hydroxylase (TH) immunostaining and induced depressive and anxiolytic-like behavioural changes. The behavioural changes were indicated by a significant increase in the immobility duration in a tail-suspension test, and an increase in the time spent in the light box in a light/dark box test. Pre-administration of quetiapine significantly alleviated the decreased TH immunostaining and attenuated the depressive and anxiolytic-like behavioural changes induced by GCI. These results enhance our understanding about the mechanisms of quetiapine and suggest a wider perspective for the clinical use of quetiapine.
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PMID:Quetiapine attenuates the depressive and anxiolytic-like behavioural changes induced by global cerebral ischemia in mice. 1756 96

Quetiapine, a new atypical antipsychotic drug, has beneficial effects on cognitive impairment and neuropathological changes in treating chronic neurodegenerative diseases. Our previous studies have demonstrated that quetiapine may have neuroprotective properties. In the present study, we investigated the effects of a 2-week pre-administration of quetiapine (10 mg/kg/day, i.p.) on spatial memory impairment and hippocampal neurodegeneration induced by 60-minute bilateral common carotid artery occlusion (CCAO). Following a 7-day recovery phase from CCAO, the spatial memory of the mice was tested using a modified water maze test. After the behavioural test, the mice were sacrificed and brain sections were stained with NeuN (a neuron-specific soluble nuclear antigen), cresyl violet (Nissl), and Fluoro-Jade B. CCAO significantly induced spatial memory impairment and caused neurodegeneration in the hilus of hippocampus, while quetiapine significantly attenuated these changes. This is the first study showing that quetiapine significantly attenuates CCAO-induced spatial memory impairment and this improvement parallels the alleviative effects of quetiapine on CCAO-induced neurodegeneration in the hilus of hippocampus. The results suggest that quetiapine may have defending effects on the impairments induced by cerebral ischemia, which enhances our understanding about the mechanisms of quetiapine.
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PMID:Quetiapine attenuates spatial memory impairment and hippocampal neurodegeneration induced by bilateral common carotid artery occlusion in mice. 1763 10

In order to determine the differential effects of flavonoids on cerebral ischemia, we investigated the effects of (-)-epigallocatechin gallate (EGCG), catechin, rutin, and quercetin on spatial memory impairment and neuronal death induced by repeated cerebral ischemia in rats. Both rutin and quercetin (50 mg/kg x 2) improved spatial memory impairment in the 8-arm radial maze task and neuronal death in the hippocampal CA1 area; however, catechin (200 mg/kg x 2) and EGCG (50 mg/kg x 1) did not. Administration of EGCG (50 mg/kg x 2) resulted in a high mortality rate. These results suggest that in this repeated cerebral ischemia model, the 4-oxo group and the 2,3-double bond in the C ring of rutin and quercetin are related to their neuroprotective action.
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PMID:Neuroprotective effects of quercetin and rutin on spatial memory impairment in an 8-arm radial maze task and neuronal death induced by repeated cerebral ischemia in rats. 1766 65

The present study investigated the neuroprotective effect of gamma-glutamylethylamide (theanine), a component Japanese green tea (Camellia sinensis), on memory impairment induced by twice-repeated cerebral ischemia in rats. Theanine was injected i.p. immediately after the first occlusion. Theanine (0.3 and 1 mg/kg) significantly prevented the impairment of spatial memory in rats subjected to repeated cerebral ischemia, 7 days after the second reperfusion. Moreover, theanine (1 mg/kg) significantly inhibited the decrease in the number of surviving cells in the hippocampal CA1 field in the same rats. These results suggest that theanine prevents memory impairment induced by repeated cerebral ischemia, in part by protecting against neuronal cell death, and that it might be useful for preventing cerebrovascular disease.
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PMID:Theanine prevents memory impairment induced by repeated cerebral ischemia in rats. 1770 46

Lithium is a major drug used for the treatment of bipolar mood disorder and has recently been shown to have neuroprotective properties. In this study we investigated the neuroprotective effects of lithium in gerbils subjected to global cerebral ischemia, an animal model of stroke. The ischemia-induced exploratory behavior changes, measured by open field testing, were largely suppressed by lithium treatment for 7 days prior to ischemic onset. Similarly, memory impairments, measured by T-maze testing, were prevented by lithium pretreatment. This is believed to be the first report of lithium-induced protection against hyperactivity in a novel open field and memory impairment in a gerbil model of global ischemia. These behavioral benefits were associated with an increase in viable cells as measured by hematoxylin and eosin staining and a decrease in apoptotic TUNEL-positive cells in the CA1 hippocampal area of ischemic gerbils. Moreover, the lithium-induced neuroprotection was accompanied by down-regulation of pro-apoptotic p53 in the CA1 but up-regulation of anti-apoptotic Bcl-2 and heat shock protein 70 (HSP70) in the ischemic brain. These results underscore the ability of lithium to improve functional behavioral outcome in gerbil and rodent cerebral ischemic models and further indicate the potential therapeutic use of lithium in certain human stroke conditions.
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PMID:Lithium reduces ischemia-induced hippocampal CA1 damage and behavioral deficits in gerbils. 1802 86

The purpose of the present study was to examine the effect of beta-amyloid (Abeta) oligomers, not the fibrils that make up Abeta plaques, on spatial memory and the cholinergic system in rats. Recently, several researchers have suggested that small assemblies of Abeta, Abeta oligomers, caused memory loss during the early stages of Alzheimer's disease without showing cell death. In the present study, the combination of Abeta oligomers and cerebral ischemia, but not cerebral ischemia alone, significantly impaired spatial memory without apoptosis in the CA1 region of the hippocampus. Donepezil, an acetylcholinesterase inhibitor, ameliorated this memory impairment. Therefore we examined acetylcholine (ACh) release from the dorsal hippocampus. A microdialysis study showed that spontaneous release of ACh was not significantly decreased by the combination of Abeta oligomers and cerebral ischemia; however, high K(+)-evoked ACh release was decreased. These results suggest that a combination of Abeta oligomers and cerebral ischemia induces memory impairment by cholinergic synapse dysfunction without apoptosis. This model may be useful for developing new drugs for the treatment of early-phase Alzheimer's disease.
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PMID:Spatial memory impairment without apoptosis induced by the combination of beta-amyloid oligomers and cerebral ischemia is related to decreased acetylcholine release in rats. 1818 22

The present study is aimed at evaluating the functional and neuroprotective effect of benzamide, a poly-(ADP-ribose) polymerase (PARP) inhibitor on delayed neuronal death (DND) in hippocampus CA1 region and memory impairment following global cerebral ischemia (GCI) in a mouse model. GCI was induced by bilateral common carotid artery occlusion (BCAo) for 20 min followed by reperfusion for 9 days. Postischemic continuous treatment with benzamide (160 mg/kg b w i.p. for 9 days) significantly reversed the GCI-induced anterograde memory impairment in passive avoidance step through and elevated plus maze tasks. The observed memory impairment in vehicle treated ischemia group was found to be well correlated with DND and downregulation of cholinergic muscarinic receptor-1 expression, which was possibly mediated by inflammation and apoptosis, as revealed from inducible nitric oxide synthase (iNOS) expression and number of TUNEL positive neurons in hippocampus CA1 region. It is clear from the present experiment that benzamide treatment significantly decreases the iNOS expression and number of apoptotic neurons and thereby improves the neuronal survival and memory during GCI. Our present findings provide compelling evidence that multiple doses of benzamide treatment is a promising therapeutic approach for cerebrovascular and neurodegenerative diseases, which deserves further clinical evaluation.
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PMID:Benzamide protects delayed neuronal death and behavioural impairment in a mouse model of global cerebral ischemia. 1850 76

Cognitive deficits, including spatial memory impairment, are very common after ischemic stroke. Neurogenesis in the dentate gyrus (DG) contributes to forming spatial memory in the ischemic brain. Fluoxetine, a selective serotonin reuptake inhibitor, can enhance neurogenesis in the hippocampus in physiological situations and some neurological diseases. However, whether it has effects on ischemia-induced spatial cognitive impairment and hippocampal neurogenesis has not been determined. Here we report that fluoxetine treatment (10 mg kg(-1), i.p.) for 4 weeks promoted the survival of newborn cells in the ischemic hippocampus and, consequently, attenuated spatial memory impairment of mice after focal cerebral ischemia. Disrupting hippocampal neurogenesis blocked the beneficial effect of fluoxetine on ischemia-induced spatial cognitive impairment. These results suggest that chronic fluoxetine treatment benefits spatial cognitive function recovery following ischemic insult, and the improved cognitive function is associated with enhanced newborn cell survival in the hippocampus. Our results raise the possibility that fluoxetine can be used as a drug to treat poststroke spatial cognitive deficits.
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PMID:Chronic fluoxetine treatment improves ischemia-induced spatial cognitive deficits through increasing hippocampal neurogenesis after stroke. 1871 44


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