Effects of enriched environment on A1/A2 phenotype conversion of astrocytes and cognitive function in rats after ischemia reperfusion
Objective:To explore the effect of enriched environment on the A1/A2 phenotype conversion of astrocytes and cognitive function in rats after ischemia-reperfusion (I/R) in rats. Method:Forty two adult male SD rats (weight 220±20g) were selected for middle cerebral artery occlusion (MCAO) surgery,followed by reperfusion 2 hours later. Three days after operation,30 rats were randomly di-vided into standard environment group (n=15) and enriched environment group (n=15),and 10 rats were se-lected as sham operation group. The enriched environment group was raised in the enriched environment cag-es,and the other two groups were raised in the standard environment. After 21 days,the Bederson score and mNss score were used to detect the behavioral changes of rats in each group,and the Morris water maze was used to detect the cognitive function of rats. Subsequently,western blot analysis was used to analyze the acti-vation of glial fibrillary acidic protein (GFAP),a marker of astrocytes. Real-time PCR and ELISA detect the expression of A1 type astrocyte marker (C3) and A2 type astrocyte marker (S100A10). Hematoxylin eosin (HE) staining was used to observe the pathological changes of cortex around the infarction. TUNEL staining was used to detect apoptosis.Result:Compared with SE group,the expression of GFAP protein in EE group decreased significantly(P<0.05). The expression level of the A1 type astrocyte marker C3 in EE group was significantly lower than that in SE group (P<0.05),while the expression of A2 type astrocyte marker S100A10 was significantly higher than that in SE group (P<0.05). Correspondingly to this result,in the EE group,the secretion of the cyto-kine TNF-α by A1 astrocytes was significantly lower than in the SE group(P<0.05),and the secretion of the cytokine BDNF by A2 astrocytes was significantly higher than in the SE group (P<0.05). TUNEL and HE staining showed that the apoptosis and damage of cells in EE group were less (P<0.05). In addition,the neu-rological ischemia in the EE group was less severe,including significant differences in the Bederson score and mNss score (P<0.01). Compared with the SE group,the rats in the EE group had better cognitive func-tion,characterized by shorter latency (P<0.05),longer residence time in the target quadrant (P<0.01),and more times of crossing the platform (P<0.05) in the water maze experiment.Conclusion:The enriched environment can inhibit the activation of astrocytes,promote the conversion of acti-vated astrocytes to neuroprotective type A2 and inhibit their conversion into neurotoxic type A1,resulting in improving cognitive function after ischemic stroke in rats.
ischemia reperfusionenriched environmentastrocyteratscognitive function
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