Nimodipine improves the disruption of spatial cognition induced by cerebral ischemia

The direct neuroprotective effect of nimodipine, a central Ca antagonist, was investigated in in vitro experiments. Also, in in vivo experiments, the effects of nimodipine and amlodipine, a noncentral Ca antagonist, on rat cerebral ischemia models developing by different mechanisms were compared. In an in vitro ischemic model using acidotic and hypoglycemic rat cerebellar granule cells, nimodipine directly protects against brain neuronal cell damage. In in vivo models of single (one 10-min, four-vessel occlusion) and repeated rat cerebral ischemia (two 10-min, four-vessel occlusions; a 50-min interval), the impairment observed 24 h after the single ischemic procedure was likely to be prevented by nimodipine (0. 1-5mg/kg, i.p.). At 7 days after the repeated cerebral ischemia, the disruption of spatial cognition was significantly prevented by nimodipine (5 mg/kg, i.p.) but not amlodipine (5 mg/kg, i.p.), which was given after each ischemia. These results indicated that nimodipine may protect neuronal cells by a more persistent mode of action, that is, nimodipine may enter into the cell and control the intracellular Ca ion cascade by inhibiting excessive Ca(2)+ influx into the mitochondria.