It remains unknown if tissue acidosis contributes to neuronal loss dur
ing cerebral ischemia. We report that brief intracellular acidificatio
n (pH 6.62) results in delayed neuronal loss in cultured hippocampal s
lices. Cell loss was located primarily in stratum pyramidale and the h
ilus suggesting that neurons were preferentially damaged. Removal of m
olecular oxygen greatly attenuated cell loss suggesting that generatio
n of reactive oxygen species may underlie acidosis-induced toxicity. T
hese data suggest that acidosis and incomplete anoxia contributes to t
he delayed neuronal loss in the ischemic penumbra.