Effects of ebselen on cerebral ischemia and reperfusion evaluated by microdialysis

Since ebselen is known to have glutathione peroxidase-like activity and inhibitory effects on lipoxygenase and cyclo-oxygenase, we investigated its protective effects against cerebral ischemia in the rat using microdialysis. Ebselen was given through a gastric tube 30 min before occlusion in the experimental groups. Ischemia was induced using 4-vessel occlusion either transiently (20-min occlusion of the arteries followed by reperfusion), or over a prolonged period (120-min occlusion). Extracellular lactate, pyruvate and purine catabolites were sampled using microdialysis and measured by high performance liquid chromatography. During ischemia, the level of lactate, adenosine, inosine and hypoxanthine in the control group increased markedly. The lactate: pyruvate ratio increased during ischemia and decreased after reperfusion. Although the level of lactate and adenosine decreased immediately after reperfusion, those of inosine and hypoxanthine showed delayed decrease. Ebselen reduced the maximum values of lactate and purine catabolites significantly and markedly in transient ischemia. Although it reduced the values significantly in prolonged ischemia, the decrements were less marked than those in transient ischemia. Based on these results we consider ebselen to protect against ischemic metabolic changes and to accelerate the recovery during reperfusion.