Correlation between hippocampal neuronal damage and spatial learning deficit due to global ischemia.

Global cerebral ischemia leads to selective neuronal damage in the CA1 sector of the hippocampus and in the striatum. This ischemia leads to a deficit in spatial learning and memory in the water maze. The results of earlier studies that have examined the relationship between neuronal damage and the deficit in the water maze were not clear-cut. It has been observed that neuroprotection reduces both the deficit in the water maze and the neuronal damage. The present study therefore approached the relationship between the neuronal damage and the deficit in the water maze by pharmacological means. Global cerebral ischemia was induced in male Wistar rats by four-vessel occlusion for 20 min. Ischemic rats were then treated with the noncompetitive non-NMDA receptor antagonist GYKI 52466 (30 mg/kg), the radical scavenger LY 231617 (20 mg/kg), the inhibitor of protein kinase C staurosporine (0.1 mg/kg), or solvent. Treatment with GYKI 52466 or LY 231617 reduced the deficit in spatial learning by limiting the increase in swim distance due to ischemia. In addition, LY 231617 reduced the deficit in spatial memory as demonstrated by minimizing the ischemia-induced reduction in time spent in the quadrant of the former platform position during the probe trial. Staurosporine had no influence on the ischemia-induced behavioural changes. Histological examination revealed neuronal damage in the hippocampus and in the striatum in all of the ischemic rats. However, treatment with GYKI 52466 or LY 231617 reduced the hippocampal damage. Correlation analysis demonstrated a correlation between hippocampal damage and total swim distance (r = 0.88, P < 0.001). No correlation was found between hippocampal damage and quadrant time of the probe trial (r = -0.24, p > 0.1). No correlation was observed between striatal damage and either total swim distance of the escape trials (r = 0.28. p > 0.1) or quadrant time of the probe trial (r = -0.08, p > 0.6). It is concluded that a correlation exists between hippocampal damage and the deficit in spatial learning following global cerebral ischemia.