Abstract

Intracellular calcium toxicity appears to play a major role in cell death during cerebral ischemia. Such calcium enters the cell mainly through the N-methyl-D-aspartate subclass of the postsynaptic glutamate receptor. Increased extracellular hydrogen ion concentration has been shown recently to reduce N-methyl-D-aspartate-activated divalent cation currents. Therefore, we studied the effect of induced brain acidosis, via hypercarbic ventilation, as a potential therapeutic modality in focal cerebral ischemia. Brain acidosis reduced infarct volume in a biphasic manner, with maximal protection at approximately brain pH 6.8. The effect was lost at pH 6.5, presumably due to the effect of acidosis on glial glutamate uptake.