Acidification is observed in stroke ranging between pH 6.1 and 6.5 in focal and global ischemia. This acidification induces deleterious effects including release of protease and calcium, activation of acid-sensing ion channels, mitochondrial destruction, and more. The pathological aspects of acidification have been well documented; nonetheless our understanding of how pH contributes to neuronal death in cerebral ischemia is still incomplete. Here, we examined the vulnerability of NBCn1 knockout mice to neuronal death induced by brain insults. Compared to wild-type littermates, NBCn1 knockout mice develop low plasma and CSF pH. To determined neuroprotective effect, mice were administered with NMDA (75 mg/kg body weight; intraperitoneal injection; 8 males for each group of knockouts and wild types). Knockout mice showed substantially reduced expression and activity of active caspase-3, and low TUNEL staining. Thus, knockout mice exhibit reduced neuronal death. In cultures of hippocampal neurons from postnat...