p38 MAPK의 저해제인 SB203580 의 국소허혈 동물모델에대한 뇌신경계 보호효과

초록

Several lines of evidence suggest a role of p38 MAPKs in inflammatory and apoptotic processes in various cell types. We have reported the delayed and differential induction of p38a and p38b MAPKs in microglia and astrocytes, respectively, in rat brain following one-hour middle cerebral artery occlusion (MCAO) and reperfusion. Here we showed that the intraventricular administration of SB203580, a p38 MAPK inhibitor, reduces infarction volume by more than 50% when administration was performed 30 min before MCA occlusion. The infarction volume was reduced by 20 % when SB203580 was administered even 1 day after MCA occlusion, indicating that SB203580 affords brain protective effect with a wide range of therapeutic window. The protective effect of p38 MAPK inhibition envisioned by decreasing infarction volume was apparent in cortex compared to the striatum. The treatment significantly inhibits morphological activation of microglia in the infarction core and moderately inhibits astrogliosis. The robust neuroprotective effect of SB203580 indicated the crucial role of p38 MAPK pathways in ischemic stroke.