Mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 deficiency protects brain from ischemic injury in mice

Abstract

Mitogen-activated protein (MAP) kinase-activated protein kinase 2 (MK2) is one of several kinases directly regulated by p38 MAP kinase. A role of p38 MAP kinase in ischemic brain injury has been previously suggested by pharmacological means. In the present study, we provide evidence for a role of MK2 in cerebral ischemic injury using MK2-deficient (MK2-/-) mice. MK2-/- mice subjected to focal ischemia markedly reduced infarct size by 64 and 76% after transient and permanent ischemia, respectively, compared with wild-type mice. Furthermore, MK2-/- mice had significant reduction in neurological deficits. Real-time PCR analysis identified a significantly lower expression in interleukin-1β mRNA (53% reduction) but not in tumor necrosis factor-α mRNA in MK2-/- mice over wild-type animals after ischemic injury. The significant reduction in interleukin-1β was also confirmed in MK2-/- mice by enzymelinked immunosorbent assay. The marked neuroprotection from ischemic brain injury in MK2-/- mice was not associated with the alteration of hemodynamic or systemic variables, activation of caspase-3, or apoptosis. Our data provide new evidence for the involvement of MAP kinase pathway in focal ischemic brain injury and suggest that this effect might be associated with the expression of interleukin-1β in the ischemic brain tissue.