Role of P38 mitogen-activated protein kinase on Cx43 phosphorylation in cerebral vasospasm after subarachnoid hemorrhage

Abstract

Objectives: Cx43 phosphorylation is involved in the pathogenesis of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). However, the exact phosphorylation mechanism of Cx43 in CVS is not fully elucidated. Thus, we examined the role of P38MAPK in CVS and Cx43 phosphorylation, using a double hemorrhage rat model.Methods: Sprague–Dawley rats weighing 300–350 g were grouped into sham, SAH, vehicle, and SAH + SB203580. SAH was induced by double injecting blood into the prechiasmatic cisterns. Neurological score was measured with the Garcia scoring system, and the diameters of basilar arteries and the expression of pCx43, pP38MAPK, and P38MAPK proteins were measured through pressure myograph measurement and Western blot analysis, respectively.Results: The neurological scores remarkably decreased after SAH but remarkably improved after SB203580 was used. The results of pressure myograph analysis on the SAH and vehicle groups showed the considerable narrowing of the basilar arteries in comparison with that of the sham group. By contrast, the arterial diameters in the SAH + SB203580 group were much larger than those observed in the SAH and vehicle groups. Moreover, the P38MAPK expression in the sham group had no substantial change in contrast to the SAH and vehicle groups, and pCx43 and pP38MAPK increased in the SAH and vehicle groups. Meanwhile, the SAH + SB203580 group showed marked decrease in Cx43 and P38MAPK phosphorylation levels relative to the SAH and vehicle groups.Conclusions: P38MAPK pathway facilitates the development of CVS through the upregulation of Cx43 phosphorylation.