These initial attempts at targeting GluN2B-PSD-95-nNOS signaling pathway for the treatment of stroke was quickly followed by a well-designed study in a focal ischemia model in gyrencephalic nonhuman primates (Cook et al., 2012a,b) and a successful phase 2, double-blind, placebo-controlled multicenter clinical trial of neuroprotection in procedurally-induced stroke (Hill et al., 2012). This evidence concerns the gene NOS1 and Stroke.