INHIBITION OF TYROSINE PHOSPHORYLATION PREVENTS DELAYED NEURONAL DEATH FOLLOWING CEREBRAL-ISCHEMIA

Protein tyrosine phosphorylation plays an important role in the regula tion of neuronal function. We examined the effects of inhibition of ty rosine phosphorylation on ischemic neuronal damage in the CA1 region o f the hippocampus. In the gerbil hippocampus, genistein and lavendusti n A, tyrosine kinase inhibitors, were administered 30 min before initi ation of 5-min ischemia and reperfusion. Both genistein and lavendusti n A blocked tyrosine phosphorylation and prevented delayed neuronal de ath (DND). However, genistin, an inactive analogue of genistein, did n ot block DND. Genistein was dose-dependent in the inhibition of DND af ter ischemia and reperfusion. Administration of genistein 5 to 10 min after ischemia and reperfusion was ineffective in blocking DND in the CA1 region of the hippocampus. The tyrosine kinase inhibitors selectiv ely blocked the phosphorylation of microtubule-associated protein (MAP )-2 kinase following ischemia and reperfusion injury. These results su ggest that tyrosine phosphorylation in the ischemic brain is important for neuronal injury and that MAP-2 kinase may play a role in the onse t of delayed neuronal death.