Background and Purpose—Ischemic postconditioning, a brief episode of ischemia after a prolonged ischemic insult, has been found to reduce the delayed neuronal loss after stroke. However, the mechanisms underlying such endogenous neuroprotective strategy remain obscure. In this study, we try to explore the excitatory postsynaptic signal events associated with neuroprotective effect of ischemic postconditioning. Methods—Global cerebral ischemia was induced for 15 minutes by the 4-vessel occlusion method in male Sprague–Dawley rats. Ischemic postconditioning was conducted 10 minutes later by a single reocclusion for 3 minutes. Results—A severe global cerebral ischemia after 5 days of reperfusion destroyed almost all hippocampal CA1 pyramidal neurons. A brief ischemic postconditioning robustly reduced the neuronal loss after ischemia. Preadministration of phosphoinositide 3-kinase inhibitor LY294002 blocked the neuroprotection of postconditioning, whereas mitogen-activated protein kinase kinase 1 inhibitor PD...
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