Role of ketamine in decreasing neuronal apoptosis caused by brain ischemia in rats with hyperglycemia

AIM: To investigate the mechanism by which ketamine reduces the aggravation of hyperglycemia-induced cerebral ischemic lesion.METHODS: Rats with normoglycemia,hyperglycemia,or hyperglycemia pretreated with ketamine injection were subjected to 15 min of global brain ischemia,and then reperfused for 0.5,1,and 3 h,respectively.Phosphorylation of extracellular signal-regulated kinase (ERK)1/2 was assessed by immunohistochemistry and Western blot analysis.Meanwhile,the neuronal apoptosis was observed by TdT-mediated dUTP nick-end labeling(TUNEL).RESULTS: The phosphorylation of ERK1/2 in the regions of cingulum cortex,hippocampus CA1 and CA3,were significantly increased in ischemic rats with normoglycemia reperfused for 0.5 h.Compared to the normoglycemic group,the phosphorylation of ERK1/2 in the regions of cingulum cortex and hippocampus CA3 were also significantly increased in hyperglycemic group reperfused for 0.5 h,which lasted to 3 h of reperfusion.However,this augmentation of phosphorylation was(depressed) by ketamine administration in hyperglycemic rats.The(extent) of ERK1/2 phosphorylation was consistent with the ischemic brain lesions,observed by histology as neuronal apoptosis.CONCLUSION: Hyperglycemia may increase the ischemic insult via the modulation of ERK1/2 signal transduction pathways.Ketamine improves the aggravation of hyperglycemia-induced cerebral ischemic lesion.This is probably mediated by inhibition of(NMDA)-mediated calcium influx,and hyperglycemia-induced phosphorylation of ERK1/2.