Neuroprotective effect of Akt activation on neurons of hippocampal CA3 regions after cerebral ischemia-reperfusion

Objective To explore the neuroprotective effect of serine-threonine protein kinase B (Akt) on neurons of hippocampal CA3 regions after cerebral ischemia-reperfusion (I/R). Methods Cerebral ischemia was induced by four-vessel occlusion in SD rats, then the rats were decapitated at 0, 30 min, 3 h, 6 h, 12 h, 1 d and 3 d after ischemia, and the time courses of the expression and phosphorylation of Akt1 after I/R in hippocampal CA3 regions were investigated using Western blot. The effect of LY294002 (a specific inhibitor of the PI3K/Akt) on p-Akt1 expression and neuronal survival in hippocampal CA3 regions was examined by immunohistochemical staining and cresyl violet staining, respectively. Results Compared to sham group, p-Akt1 expression was significantly increased at 30 min(P<0.05) and reached peak at 3 h of reperfusion, and remained a high level until 3 d in hippocampal CA3 regions (P<0.05). Pretreatment with LY294002, significantly decreased p-Akt1 immunoreactivity compared with the R6 h group (the positive cells: R6 h, 134. 6±7.8/mm2; LY294002+ R6 h, 54.8±5.1/mm2) (P<0.05), and aggravated the injury of neurons in hippocampal CA3 regions, compared with the R5 d group (the neuronal density: R5 d, 152.0±17.4/mm2; LY294002+ R5 d, 62.7±5.1/mm2) (P<0.05). Conclusion The activation of Akt induced by ischemic stress plays an important role in neuronal survival of hippocampal CA3 region. Key words: Cerebral ischemia-reperfusion; Protein kinase B; Hippocampal CA3 region