Role of the P38 Mitogen-activated Protein Kinase/cytosolic Phospholipase A2 Signaling Pathway in Blood-brain Barrier Disruption After Focal Cerebral Ischemia and Reperfusion

Overview

Journal J Cereb Blood Flow Metab

Publisher Sage Publications

Specialties Cardiology & Vascular Diseases
Endocrinology
Neurology

Date 2008 Jun 12

PMID 18545259

Citations 68

Authors

Chikako Nito

Hiroshi Kamada

Hidenori Endo

Kuniyasu Niizuma

D Jeannie Myer

Pak H Chan

Affiliations

Soon will be listed here.

Abstract

Cytosolic phospholipase A(2) (cPLA(2)) is a key enzyme that mediates arachidonic acid metabolism, which causes cerebral ischemia-induced oxidative injury, blood-brain barrier (BBB) dysfunction, and edema. Recent reports have shown that p38 mitogen-activated protein kinase (MAPK) is related to phosphorylation and activation of cPLA(2) and release of arachidonic acid. However, involvement of the p38 MAPK pathway in cPLA(2) activation and of reactive oxygen species in expression of p38 MAPK/cPLA(2) after ischemia-reperfusion injury in the brain remains unclear. To address these issues, we used a model of transient focal cerebral ischemia (tFCI) in rats. Western blot analysis showed a significant increase in expression of phospho-p38 MAPK and phospho-cPLA(2) in rat brain cortex after tFCI. Activity assays showed that both p38 MAPK and cPLA(2) activation markedly increased 1 day after reperfusion. Intraventricular administration of SB203580 significantly suppressed activation and phosphorylation of cPLA(2) and attenuated BBB extravasation and subsequent edema. Moreover, overexpression of copper/zinc-superoxide dismutase remarkably diminished activation and phosphorylation of both p38 MAPK and cPLA(2) after reperfusion. These findings suggest that the p38 MAPK/cPLA(2) pathway may promote BBB disruption with secondary vasogenic edema and that superoxide anions can stimulate this pathway after ischemia-reperfusion injury.

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