Posttreatment with EPC-K1, an inhibitor of lipid peroxidation and of phospholipase A2 activity, reduces functional deficits after global ischemia in rats.

In this study the effect of an inhibitor of lipid peroxidation and of phospholipase A2 activity, EPC-K1, on spatial learning deficit and neuronal damage following transient cerebral ischemia was evaluated. Global ischemia was induced by four-vessel occlusion (4VO) for 20 min in rats. EPC-K1 (10 mg/kg IP) was administered either a) 15 min before induction of ischemia, b) immediately after, or c) 30 min after onset of reperfusion. One week after surgery spatial learning was tested in the Morris water maze. EPC-K1 reduced the deficit in spatial learning when given immediately or 30 min after the onset of reperfusion but not when applied 15 min before ischemia. Neuronal damage in the CA1 sector of the hippocampus produced by 4VO was slightly, but not significantly attenuated by posttreatment. The present data demonstrate that posttreatment with EPC-K1 exerts a protective effect on deficits in spatial learning induced by 4VO. These results support the hypothesis that lipid peroxidation and activation of phospholipase A2 contribute to functional alterations of the brain during reperfusion following forebrain ischemia.