NMDARs in Cell Survival and Death: Implications in Stroke Pathogenesis and Treatment

Stroke is a leading cause of death and disability in developed countries. N-methyl-D-aspartate glutamate receptors (NMDARs) have important roles in stroke pathology and recovery. Depending on their subtypes and locations, these NMDARs may promote either neuronal survival or death. Recently, the functions of previously overlooked NMDAR subtypes during stroke were characterized, and NMDARs expressed at different subcellular locations were found to have synergistic rather than opposing functions. Moreover, the complexity of the neuronal survival and death signaling pathways following NMDAR activation was further elucidated. In this review, we summarize the recent developments in these areas and discuss how delineating the dual roles of NMDARs in stroke has directed the development of novel neuroprotective therapeutics for stroke.