DIFFERENTIAL INDUCTION OF p38a AND p38b MAPK ISOFORMS IN MICROGLIA AND ASTROCYTES AFTER TRANSIENT FOCAL ISCHEMIA IN RAT

초록

Several lines of evidence suggest a role of p38 MAPKs in inflammatory and apoptotic processes in various cell types. Here we report the biphasic and distinct induction of p38a and p38b MAPKs in rat brain following one-hour middle cerebral artery occlusion (MCAO). The kinase activities of both p38a and p38b were increased within 30 min after ischemic insult, and the immediate induction of the kinase activities returned to the basal level in an hour. The second surge of the p38a activation was observed around 2 days after ischemia-reperfusion, whereas the second surge of the p38b induction occurred around 4 days after ischemic insult. Interestingly, the increased expression of p38a during the second surge was found in microglia cells in the infarction core as well as the peri-infarction area. In contrast, p38b was increased in the nucleus and proximal parts of the axon and dendrites of neurons during the early induction, whereas it was induced in reactive astrocytes in the peri-infarction area during the second round of induction. The differential and protracted induction of p38a and p38b MAPKs in microglia and astrocytes, respectively, was closely matched to the activation processes of each glia cell type in post-ischemic brain. These results suggest distinct roles of p38 MAPK isoforms in the activation of different glia cell types in the post ischemic brain.