Effects of hyperglycemia on the activation of microglia in focal cerebral ischemia and reperfusion / 解放军医学杂志

ABSTRACT

Objective To observe the changes of microglia in diabetic cerebral ischemia and reperfusion,and further explore the role of microglia in diabetic rats with cerebral ischemic injury.Methods Eighty healthy male SD rats were randomly divided into 4 groupsnormal blood glucose sham operation group (NG sham group,n=5),diabetic hyperglycemia sham operation group (HG sham group,n=5),normal blood glucose with cerebral ischemia-reperfusion group (NG MCAO group,n=35) and diabetic hyperglycemia with cerebral ischemia-reperfusion group [HG middle cerebral artery occlusion (MCAO) group,n=35].The diabetic rats models were established by intraperitoneal injection of streptozotocin (STZ).The cerebral ischemia reperfusion models were made with MCAO,the specific marker protein Iba-1 was used to immunohistochemically label the microglia.The changes of microglia in the periventricular zone and caudate putamen region of the rats in HG MCAO group and NG MCAO group were observed at ischemia 30min and reperfusion 30min,3h,6h,Id,3d,7d and 14d (each time point contains 5 rats).Iba-1 and proliferating cell nuclear antigen (PCNA) immunofluorescence double labeling method were performed to detect the proliferation of microglia.Results After ischemia-reperfusion,the brain tissue appeared as obvious edema,mesh-like,HE staining faded,neurons swelled,cytoplasm vacuolization,nuclear pyknosis,and inflammatory cell infiltration.All these symptoms of brain injury were more obvious in HG group than in NG group.On the 3rd day after ischemia reperfusion,microglial cells were markedly activated in the infarct peripheral zone,piriform cortex and somatic sensory cortex,the activation reached the peak value at the 7th day,and the activated state continued to the 14th day of reperfusion.It was found with Iba-1 and PCNA immunofluorescence double labeling that,after cerebral ischemia-reperfusion,the increase of microglia number was related to its proliferation.The microglia proliferation also increased at the 3rd day after ischemia-reperfusion,and reached the peak value at the 7th day.The degree of microglia activation and proliferation was weaker in NG group than in HG group (P＜0.05),but higher obviously when compared with their each sham group (P＜0.05).Conclusion Hyperglycemia induced ischemia brain tissue microglia activation and proliferation inhibition may be involved in the hyperglycemia induced ischemic brain damage.