LBP appears to have broad benefits in a variety of injury types by regulating different pathways. Based on the idea that different NMDA receptor subunits have distinct functions, we hypothesized that LBP exhibits its neuroprotective effect against ischemic injury by regulating NR2A and NR2B signaling pathways. The present study investigated the underlying mechanisms of LBP-induced neuroprotection in in vivo ischemia and in vitro oxygen-glucose deprivation (OGD) models and unraveled that indeed both NR2A and NR2B receptor signaling pathways play crucial role in the actions of LBP.