| Background:Ischemic stroke is the one of most common diseases of the nervous system. With the development of thrombolysis treatment, and interventional treatment techniques, secondary brain injury after ischemia-reperfusion has been gradually paid more attention to. The aim of neuroprotection is to prevent delayed neuron injury of the zone of the ischemic penumbra. Memantine (1-amino-3,5-dimethyladamantane), as a neuro protectant, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been widely used for Parkinson's disease, senile dementia, spastic diseases and the viral infectious disease in the past clinical practice, showing no serious side effects. For the treatment of ischemic stroke, research has focused on inhibition of excitatory amino acids and calcium influx in the past. The mechanisms of preventing secondary injury after ischemia-reperfusions still need further exploration. Inhibition of caspase 3 activity blocks apoptosis response, and protection against lipid peroxidation of lipid membrane stability may be related mechanisms. In this study, the effect of memantine on caspase-3 activity and MDA releasing were observed in cerebral ischemia-reperfusion models, in order to investigate the neuroprotective mechanism of NMDA receptor antagonist.Objective:To observe the inhibition of NMDA receptor antagonist on the delayed injury of ischemia-reperfusion in rats model. To investigate neuro protective mechanism of NMDA receptor antagonist on ischemia-reperfusion injury of neuron. To supply theoretical and experimental basis for clinical application.Methods:One hundred thirty-five male Wistar rats were randomly divided into 3 groups: sham-operation group, cerebral ischemia group and memantine intervention group. The model of cerebral ischemia-reperfusion injury rats was established by the middle cerebral artery occlusion (MCAO). The rats of drug group intervention were treated with memantine. The changes of cell morphology and the expression of caspase-3 in cerebral cortex neurons were observed by HE stain and immunohistochemistry technique respectively. The expression of caspase-3 enzyme activity unit and MDA levels were detected by spectrophotometer.Results:The expression of caspase-3 positive area average integrated optical density,Caspase-3 enzyme activity unit and the levels of MDA among the three groups were different, and there were significant different. The expression levels of caspase-3 and the level of MND in ischemia-reperfusion brain of memantine intervention group was lower than in cerebral ischemia model group, but higher than that in sham-operated group(P<0.05).Conclusion:NMDA receptor antagonist could suppress the expression of caspase-3 and the level of in cerebral cortex neurons and inhibit delayed injury of in neuro ischemia-reperfusion rats, playing a neuroprotective role. |
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