Faculty Directory

Research

Brain pH is an important factor that has biological and pathological impacts in the central nervous system. Acidification causes deleterious effects as it causes release of protease and calcium, activation of acid-sensing ion channels, mitochondrial destruction, and more. Paradoxically, a mild acidification has a protective effect. A mild acidification delays the onset of damage. Lowering pH to 6.9–7.3 inhibits calcium accumulation, excitotoxicity, hypoxic injury. Thus, a pH decrease is beneficial for neurons as long as it does not markedly fall to the level where deleterious effects are inevitable. Despite this current understanding, it is presently unclear how applicable regulating brain pH can be to a therapeutic approach to protection from brain damage. Understanding this regulation is extremely valuable for addressing neonatal metabolic or respiratory acidosis, which if untreated can lead to myocardial depression, seizures, or shock.

My lab focuses on the sodium bicarbonate transporter NBCn1 (SLC4A7), a pH-regulating protein that moves Na+ and HCO3– across the cell. Our study shows that NBCn1 knockout mice are less vulnerable to ischemia. In the experiments of cerebral infarction by a unilateral occlusion of the common carotid artery and hypoxia, we found that, while wild type mice showed sizable infarction, knockout mice had no discernible injury. Furthermore, these knockout mice are less susceptible to seizure and have decreased seizure severity and duration. These data suggest that NBCn1 deletion protects neurons from acute brain insults. Our finding is interesting as the data lead to the possibility that blocking NBCn1 might help protect the brain from acute insults. 

Research Center(s)

• Children’s Center for Neurosciences Research (CCNR) →