| Objectives To explore the protective effect of new AMPA receptor antagonist on cerebral infarction reperfusion injury in rats and its time window.Methods 90 male SD rats weighing 250-300 g were selected.Middle cerebral artery occlusion model in rats was made by modified longa thread occlusion method.The experimental group was divided into sham operation group(sham group),model group(MCAO group)and talampanel group(Tal Group).The treatment group(Tal Group)was divided into four subgroups: tal0 h group,tal1 h group,tal3 h group and tal5 h group.In sham group,the rats were anesthetized successfully without inserting the thread into the right middle cerebral artery,but only separated;in MCAO group,the thread was inserted into the right middle cerebral artery,blocking the blood vessels,and then the thread was withdrawn 60 minutes later to restore the blood flow.In sham group and MCAO group,the same amount of physiological saline was given through the tail vein.After MCAO model was successfully established,TAL group rats were injected with talampanel(12 mg / kg)via tail vein at 0,1,3 and 5 hours after reperfusion.In the first hour after MCAO was successfully prepared,the core temperature of rats was maintained at 36-37℃.After 24 hours,the rats in each group were scored for neurological damage;the volume of cerebral infarction was measured by TTC staining;the morphological changes of neurons in hippocampal CA1 area were observed by HE staining;the number of apoptotic cells and the number of neurons in infarcted cortex were measured by immunohistochemistry staining.Results 1 Comparison of infarct volume and nerve function defect of rats in each group: the nerve function of rats in sham group was normal,without nerve defect symptoms,without cerebral infarction.The rats in the treatment subgroups of tal and MCAO group showed different degrees of neurological deficit symptoms,and different sizes of cerebral infarction lesions could be seen in the blood supply area of middle cerebral artery.Compared with the MCAO group,the damage degree of nerve cells in each treatment sub group of Tal was significantly reduced,and the damage score of nerve function and the volume of cerebral infarction were significantly reduced(P<0.05).Among the treatment subgroups of Tal,nerve defect score and infarct volume in 0h group,1H group and 3H group were significantly lower than those in 5h group(P<0.05).2 HE staining was used to observe the neurons in the hippocampal CA1 area of rats: in the sham group,the morphology was complete,the neurons were closely arranged,the cytoplasm was transparent,and the nucleolus was clear;in the TAL treatment subgroups and MCAO group,the arrangement of neurons in the hippocampal CA1 area was disordered,the nuclei were pyknosis or necrosis,and there were different degrees of edema and degeneration between the tissues.Compared with the MCAO group,in the TAL treatment subgroups,the tissue edema and degeneration were found And the degree of degeneration of neurons was obviously reduced.3 Immunohistochemistry: in the experimental rats of each group,a large number of surviving neurons were found in the cerebral cortex of sham group,with dense arrangement and only a small number of cells expressing caspase-3.However,in MCAO group,the number of apoptotic cells in ischemic penumbra increased significantly,a large number of Caspase-3 positive cells were observed,and the number of neurons in cerebral infarction cortex decreased significantly.Compared with the MCAO group,the number of Caspase-3 cells in ischemic penumbra and the number of surviving neurons in infarcted cortex in all treatment subgroups of TAL decreased significantly(P<0.05)The results were statistically significant(P<0.05).Conclusions 1 The AMPA receptor antagonist taranpanet has a protective effect on cerebral ischemia-reperfusion injury in rats.It can reduce the neurological deficit score,cerebral infarction volume and the expression of Caspase-3 in neurons.2 When the drug was given at 5 hours after ischemia-reperfusion,the protective effect of talampanel on brain injury induced by ischemia-reperfusion was obviously weakened.Figure 10;Table 4;Reference 137... |
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