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 1/2 (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 ERK1/2 activation in hippocampus after brain ischemia may not interfere with the postischemic cell death in CA1 region.