Extracellular signal-regulated kinase 1/2 activation in hippocampus after cerebral ischemia may not interfere with postischemic cell death

To investigate the effect of the activation of extracellular signal-regulated kinase 112 (ERK1/2) on cerebral ischemic injury, temporospatial alterations of active (diphosphorylated) ERK1/2 immunoreactivity in hippocampus was examined. Western blot showed that diphosphorylated ERK1/2 were decreased at 10 min of cerebral ischemia but increased rapidly (within 2 min) and transiently (within 4 h) during reperfusion. Immunohistochemistry showed that little diphosphorylated ERK1/2 immunoreactivity was seen in CA1 pyramidal cell bodies after ischemia. while strong immunoreactivity were seen in neuronal bodies in CA3/DG and in fiber systems in both CA1 and CA3 regions. Cerebral ventricular infusion of PD98059, a specific inhibitor of ERK kinase, completely prevented ERK1/2 activation after ischemia but had no effect on the survival of pyramidal cells in CA1 subfield. The results suggest that ERK 112 activation in hippocampus after brain ischemia may not interfere with the postischemic cell death in CA1 region. (C) 2001 Elsevier Science B.V. All rights reserved.