Role of MAPK in chronic cerebral vasospasm.

This study was undertaken to investigate the role of p44/42 MAPK in a dog double hemorrhage model of subarachnoid hemorrhage (SAH), and whether MEK inhibitors can alter the degree of SAH-induced vasoconstriction. The diameter of the basilar artery, which was compared with day 0 angiogram, decreased gradually in a time-dependent manner from day 3 (80%), day 5 (68%) through day 7 (53.5%). The level of MAPK (p44/42) immunoprecipitation peaked on day 3 and remained enhanced through day 7 (P < 0.05). MEK inhibitor PD98059 significantly reduced p44/42 MAPK immunoprecipitation and significantly reversed vasospasm and increased residual diameter to 79.0% on day 7. These results demonstrated that p44/42 MAPK kinase is involved in the pathogenesis of cerebral vasospasm. The MEK inhibitor PD98059 might be useful in the treatment of vasospasm.