Ketamine to reduce high blood sugar caused by cerebral ischemia in neuronal apoptosis.docVIP

 PAGE \* MERGEFORMAT 9 Ketamine to reduce high blood sugar caused by cerebral ischemia in neuronal apoptosis Authors: Zhang Jianzhong, Jing Li, Guo Ying, Ma Yi, Wang Yi-li [Keywords:] Hyperglycemia; cerebral ischemia; ketamine; extracellular signal-regulated MAP kinase; apoptosis; immunohistochemistry; Western blot Role of ketamine in decreasing neuronal apoptosis caused by brain ischemia in rats with hyperglycemia [Abstract] AIM: To investigate the mechanism by which ketamine reduces the aggravation of hyperglycemiainduced 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 signalregulated kinase (ERK) 1 / 2 was assessed by immunohistochemistry and Western blot analysis. Meanwhile, the neuronal apoptosis was observed by TdTmediated dUTP nickend 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 hyperglycemiainduced cerebral ischemic lesion. This is probably mediated by inhibition of NMDAmediated calcium influx, and hyperglycemiainduced phosphorylation of ERK1 / 2. [Ke