SB203580 투여를 통한 허혈 후 뇌신경계 보호 효과

초록

We have previously reported the delayed and differential induction of p38a and p38b MAPKs in microglia and astrocytes, respectively, in brain following transient global ischemia. Here we report the sustained induction and activation of p38a MAPK in activating microglia in rat brain after transient middle cerebral artery occlusion (MCAO). The intraventricular administration of SB203580, a p38 MAPK inhibitor, at 30 min before MCAO reduced the infarct volume to 50% of the control, which was accompanied by the significant improvement of neurological deficits. More interestingly, the infarct volume was reduced to 72% and 77%, when SB203580 was administered 6 hrs and even 12 hrs after MCA occlusion, respectively. The induction of various factors involved in inflammatory processes, such as iNOS, TNF-a, IL-1b and COX-2, was suppressed by the administration of SB203580 at 6 hrs after MCAO. These results suggest that the sustained activation of p38 MAPK pathway and p38 MAPK associated inflammatory processes play a crucial role in postischemic brain.