It is plausible that in the early stage (1 h OGD), overexpression of NR2B and nNOS may induce the formation of a NR2B-PSD-95-nNOS complex. This complex will trigger production of NO followed by apoptosis (Christopherson et al., 1999; Sattler et al., 1999). Therefore, LBP may block the formation of the NR2B-PSD-95-nNOS complex by inhibiting expression of NR2B at the time point. At late stages (OGD for 4 h), however, when expression of NR2B was completely depressed, LBP did not further inhibit NR2B expression. LBP still prohibited overexpression of nNOS, which may be mediated through inhibiting a cascade of events related to mitochondrial injury and apoptosis, including reduction of calcium influx, mitochondrial permeability, Bad, cytC and caspase-3 levels after 4 h OGD. This is consistent with prior finding in an in vivo MCAO model (Wang T. et al., 2014). Finally, we used a NR2A inhibitor NVP-AAM077 and NR2B co-agonist D-serine to test whether the neuroprotective influence of LBP would antagonize the effect of these two drugs. Our results indicate that LBP can greatly block the action of NVP-AAM077 and D-serine, which suggests that LBP imparts its neuroprotective effects through inhibiting NR2B or activating NR2A.