AIM: To investigate the interactions among postsynaptic density 95 (PSD-95), Ca2+-calmodulin dependent protein kinase IIα (CaMKIIα), and N-methyl-D-aspartate receptor subunit 2B (NR2B) during ischemia and reperfusion in hippocampus of rats. METHODS: Brain ischemia was induced by four-vessel occlusion procedure in rats. Immu- noprecipitation and immunoblotting were performed to study the interactions and phosphorylation of proteins. The association-dissociation of PSD-95 and CaMKIIα to and from N-methyl-D-aspartate (NMDA) receptor induced by ischemia and reperfusion and the effects of 1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenyl-pip- erazine (KN-62, a selective inhibitor of CaMKII) on these protein interactions were investigated. Coimmuno- precipitation and immunoblotting were performed for the studies of interactions among proteins. RESULTS: The alternations of the binding level of PSD-95 and CaMKIIα to NR2B during ischemia and reperfusion demonstrated the negative correlation to each other. Pre-administration of KN62 through both cerebral ventricles inhibited the 10 min ischemia-induced increase of the binding of PSD-95 to NR2B and, on the contrary, promoted the binding of CaMKIIα to NR2B. CONCLUSION: PSD-95 competes with CaMKII to bind to NR2B during ischemia and reperfusion in rat hippocampus. AIM: To investigate the interactions among postsynaptic density 95 (PSD-95), Ca2 + -calmodulin dependent protein kinase IIα (CaMKIIα), and N-methyl- D-aspartate receptor subunit 2B (NR2B) during ischemia and reperfusion in hippocampus of rats. METHODS: Brain ischemia was induced by four-vessel occlusion procedure in rats. Immu- noprecipitation and immunoblotting were performed to study the interactions and phosphorylation of proteins. The association-dissociation of PSD-95 and CaMKIIα to and from N-methyl-D- aspartate (NMDA) receptor induced by ischemia and reperfusion and the effects of 1- [N, O-bis- (5-isoquinolinesulfonyl) -N-methyl- a selective inhibitor of CaMKII) on these protein interactions were investigated. Coimmuno- precipitation and immunoblotting were performed for the studies of interactions among proteins. RESULTS: The alternations of the binding level of PSD-95 and CaMKIIα to NR2B during ischemia and reperfusion. the negative correlation to each other. Pre-administration of KN62 through both cerebral ventricles inhibited the 10 min ischemia-induced increase of the binding of PSD-95 to NR2B and, on the contrary, promoted the binding of CaMKIIα to NR2B. CONCLUSION: PSD -95 competes with CaMKII to bind to NR2B during ischemia and reperfusion in rat hippocampus.