Effect of staurosporine, a protein kinase C inhibitor, on impairment of working memory in rats exposed to cerebral ischemia.

A 5-min period of cerebral ischemia induced in rats by the four-vessel occlusion method increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) assessed by a working memory procedure applied in a three-panel runway task. The protein kinase C (PKC) inhibitor, staurosporine 0.03 and 0.1 mg/kg, administered immediately after blood flow reperfusion, significantly reduced the increase in errors expected to occur 24 h after 5 min of ischemia. However, administration of staurosporine 0.1 mg/kg 6 h after ischemia had no effect on the increase in errors. The protective effect of staurosporine suggests that the enhanced PKC activity during the early reperfusion phase plays a crucial role in the post-ischemic impairment of working memory.