Activation of mitogen-activated protein kinases after transient forebrain ischemia in gerbil hippocampus

We investigated the expression, activation, and distribution of c-Jun N-ter minal kinases (JNKs), p38 mitogen-activated protein kinases (p38s) and extr acellular signal-regulated kinases (ERKs) using Western blotting and immuno histochemistry in gerbil hippocampus after transient forebrain ischemia to clarify the role of these kinases in delayed neuronal death (DND) in the CA 1 subfield. Immunoblot analysis demonstrated that activities of JNK, p38, a nd ERK in whole hippocampus were increased after 5 min of global ischemia. We used an immunohistochemical study to elucidate the temporal and spatial expression of these kinases after transient global ischemia. The immunohist ochemical study showed that active JNK and p38 immunoreactivities were enha nced at 15 min of reperfusion and then gradually reduced and disappeared in the hippocampal CA1 region. On the other hand, in CA3 neurons, active JNK and p38 immunoreactivities were enhanced at 15 min of reperfusion and peake d at 6 hr of reperfusion and then gradually reduced but was continuously de tected 72 hr after ischemia. Active ERK immunoreactivity was observed trans iently in CA3 fibers and dentate gyrus. Pretreatment with SB203580, a p38 i nhibitor, but not with PD98059, an ERK kinase 1/2 inhibitor, reduced ischem ic cell death in the CA1 region after transient global ischemia by inhibiti ng the activity of p38. These findings indicate that the p38 pathway may pl ay an important role in DND during brain ischemia in gerbil. Components of the pathway are important target molecules for clarifying the mechanism of neuronal death.