| Objective:In this study, the neuronal protective mechanism of topiramate (TPM) were observed by rat focal cerebral ischemia reperfusion model-middle cerebral artery occlusion (MCAO). It was measured the nerve function deficiency scores, infarction volume, estimated brain water content and the content of amino acids of cerebral cortex in the both TPM treated and MCAO group. It was observed change of microglia and astrocytes activation in the TPM treated group compared to the MCAO group.Methods:Healthy Male SD rats were randomly assigned to sham group、 MCAO group and TPM+MCAO group. Then they were subjected to left middle cerebral artery occlusion for 2h and reperfusion for 24h. Rats in the TPM+MCAO group were injected TPM suspension (8mg/ml,80mg/kg)3days before the initiation of the artery occlusion and the reperfusion. The nerve function deficiency scores were measured. Estimated brain water content by weighing method.The infarct volume was evaluated through TTC staining. Estimated the content of amino acids of cerebral cortex by the method of high performance liquid chromatography (HPLC) with fluorescent detection. At last we observed microglia and astrocytes types in the center of the infarcts and in cerebral ischemic penumbra by immunohistochemical staining.Result:(1) The sham group did not have neurologic deficits; The scores of the MCAO group werel.47±0.85; The scores of the TPM+MCAO group were 2.86±0.96.There were significant differences on the neurological impairment scores between the TPM+MCAO group and the MCAO group(P<0.05).(2) The percentage of infarct volume in the MCAO group was 35.28±9.24,those of the TPM+MCAO treated group was8.36±4.52. There are significant differences between two groups (P<0.05).(3) The brain water content was(75.58±2.84)% in sham group; (85.85±2.75)% in MCAO group; (79.54±1.56)% in TPM+MCAO group. TPM+MCAO group obviously reduce water content in brain tissue, there was a significant difference compared with MCAO group (P<0.05),while compared with the sham group had no significant difference (P> 0.05).(4) The concentration of Glu、 GABA in the cerebral cortex were (85.37±5.77) u mol/L、 (5.5 8±0.84) u mol/L in sham group; (106.02±21.30) u mol/L、(8.35±1.47) umol/L in MCAO group; (105.78±20.88) u mol/L、 (8.37±1.55) u mol/L in TPM+MCAO group. The concentration of Glu and GABA in the cerebral cortex of MCAO group were both increased compared with the sham group(p<0.05). TPM can significantly decrease the content of Glu(p<0.05)and increase the content of GABA(p<0.05).(5) It is mainly found some resting state of astrocytes in the sham group (Fig.3a and 3d). In the MCAO group, only less pieces of astrocytes and less activation of astrocytes were found in the center of the infarcts. However, some activated astrocytes in cerebral ischemic penumbra were observed in the cerebral ischemic penumbra (Fig.3f).(6) It is mainly observed some resting state "Fried egg" microglia in the sham group (Fig.4a and 4d). In the MCAO group, because tissue necrosis induced by serious injury, only less pieces of microglia and less activation of microglia in the center of the infarcts were found in the core of infarct. However, it was also found some activated microglia in cerebral ischemic penumbra (Fig. 3f).Conclusion:(1) TPM can improve behavior score after ischemia-reperfusion and relieve symptoms deletion of nerve.(2) TPM can protect brain tissue by reducing the infarction area, alleviating cerebral edema,and strengthen GABA release, inhibiting Glu release.(3)To a certain extent, TPM can reduce ischemia-reperfusion injury by restraining the activation of glial cell.(4) This study show that TPM not only have good antiepileptic effect, but can provide protection for ischemia-reperfusion injury. So it provided a new clinical treatment method for Cerebral infarction combined with epilepsy. |
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