Differential and delayed induction of p38α and p38β 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 differential activation of p38α and p38β MAPKs in the rat brain following transient focal cerebral ischemia. The kinase activities of p38α and p38β were strongly induced in the brain within 30 min after ischemia-reperfusion, and the immediate induction returned to the basal levels in an hour. The second surge of the p38α activation was observed around 2 days after ischemia-reperfusion, whereas the second round of induction of p38β was observed around 4 days after ischemic insult. Interestingly, the increased expression of p38α during the second surge was found in microglia cells in the infarction core as well as in the peri-infarction area. In contrast, p38β was increased initially in the nucleus of neurons during the immediate induction, whereas it was induced in reactive astrocytes in peri-infarction area during the second round of induction. Interestingly, the differential and delayed induction of p38α and p38β MAPKs in microglia cells and reactive astrocytes, respectively, was closely matched to the activation processes of each glia cell type. These results lead us to predict the distinct roles of p38 MAPK isoforms in the activation of different glia cell types in the post ischemic brain.