Apoptosis in the repeated cerebral ischemia--behavioral & histochemical study

Abstract

We have been reported that the repeated cerebral ischemia induced more severe disruption of spatial cognition than single ischemia without any other motor disturbance in 8-arm radial maze task in rats. And we have been clarified that it is corresponding with 60% of selective cell injury of the CA1 pyramidal cells in the hippocampus. Recently, characteristics of apoptosis such as internucleosomal DNA fragmentation have been found in excitotoxic neuronal death. In the present study, we investigated how necrosis and apoptosis following repeated ischemia involve to the cell death. Repeated cerebral ischemia (10 min x 2, 1 hr interval) induced significant disruption of spatial cognition not only 24 hrs but also 7 days after reperfusion. The decrease of H.E-positive neurons was found in the hippocampus CA1 area and frontal cortex within 3 days after reperfusion, while an DNA fragmentation and TUNNEL-positive neurons in the same areas were found afterward. Furthermore repeated cerebral ischemia-induced disruption of spatial cognition and apoptosis in the hippocampal CA1 area were inhibited by YM-90 K(15 mg/kg,i.p.), which is a selective AMPA/KA receptor antagonist, but not by MK-801. These results suggested that the apoptotic cell death may be occurred via non-NMDA receptor mechanism in relatively late phase of the reperfusion period and it may relate to the incidence of the disruption of spatial cognition in the rat.