Mitogen-activated Protein Kinase-activated Protein (MAPKAP) Kinase 2 Deficiency Protects Brain from Ischemic Injury in Mice*

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 enzyme-linked 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.

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