MEK/ERK- and calcineurin/NFAT-mediated mechanism of cerebral hyperemia and brain injury following NMDA receptor activation.

N-methyl-d-aspartate (NMDA) receptor activation increases regional cerebral blood flow (rCBF) and induces neuronal injury, but similarities between these processes are poorly understood. In this study, by measuring rCBF in vivo, we identified a clear correlation between cerebral hyperemia and brain injury. NMDA receptor activation induced brain injury as a result of rCBF increase, which was attenuated by an inhibitor of mitogen-activated protein kinase or calcineurin. Moreover, NMDA induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear translocation of nuclear factor of activated T-cell (NFAT) in neurons. Therefore, a MEK/ERK- and calcineurin/NFAT-mediated mechanism of neurovascular coupling underlies the pathophysiology of neurovascular disorders.