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

    ZHANG Jianª²Zhong, JING Li, GUO Fengª²Ying, MA Yi, WANG Yiª²Li

    Institute of Immunopathology, School of Life Science & Technology, Xi¬ðan Jiaotong University, Xi¬ðan 710061, China, Department of Pathology£¬Ningxia Medical College, Yinchuan 750004, China

    ¡¾Abstract¡¿ AIM: To investigate the mechanism by which ketamine reduces the aggravation of hyperglycemiaª²induced 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 signalª²regulated kinase (ERK)1/2 was assessed by immunohistochemistry and Western blot analysis. Meanwhile, the neuronal apoptosis was observed by TdTª²mediated dUTP nickª²end 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 hyperglycemiaª²induced cerebral ischemic lesion. This is probably mediated by inhibition of NMDAª²mediated calcium influx, and hyperglycemiaª²induced phosphorylation of ERK1/2. ......