Differential activation of p38 MAPKs in microglia and astrocytes following transient focal ischemia in rat

초록

Activation of p38 MAPK has been implicated in pathological changes in the course of inflammatory and apoptotic processes in various cell types including neurons. In previous report, we demonstrated that p38 MAPK shows constitutive expression in normal brain and expression patterns of two isoforms, p38α and p38β, are similar in general but distinct in that p38b is localized in astrocytes as well as in neurons. In current study, we report the differential activation of p38 MAPKα and p38 MAPKβ in the brain of rat suffered from transient focal ischemia. The immunoreactivity of p38α MAPK was markedly increased as early as 4 hrs after ischemia and continued to increase until 4 days after ischemia. The induction of p38α-immunoreactivity was concentrated in microglia located in the infarction core as well as at the peri-infarction area. The induction of p38α was accompanied by the activation of microglia, which was shown by isolectin lebeling. In contrast, the immunoreactivity for p38β was dramatically increased in reactive astrocytes mainly in peri-infarction area around 4 days after ischemic insult, and such an induction was sustained for up to 10 days after ischemia. Significant induction of p38αand p38β MAPKs in microglia and reactive astrocytes, respectively, in post-ischemic brain suggested that p38 MAPKs might play distinct but important roles in post-ischemic brain, which are related with delayed neuronal death and/or inflammatory process.