Abstract
Elevation of brain glucose before the onset of nearly complete ischemia leads to increased lactic acid within brain. When excessive, such acidosis may be a necessary factor for converting selective neuronal loss to brain infarction from nearly complete ischemia. To examine the potential neurotoxicity of excessive lactic acid concentrations, we microinjected (0.5 µl/min) 150 m
M
sodium lactate solutions (adjusted to 6.50-4.00 pH) for 20 min into parietal cortex of anesthetized rats. Interstitial pH (pH
0
) was monitored with hydrogen ion–selective microelectrodes. Animals were allowed to recover for 24 h before injection zones were examined with the light microscope. Injectants produced brain necrosis in a histological pattern resembling ischemic infarction only when pH
0
was ≤ 5.30. Nonlethal injections showed only needle tract injuries. Abrupt deterioration of brain acid-base homeostatic mechanisms correlated with necrosis since pH
0
returned to baseline more slowly after lethal tissue injections than after nonlethal ones. The slowed return of pH
0
to baseline after the severely acidic injections may reflect altered function of plasma membrane antiport systems for pH regulation and loss of brain hydrogen ion buffers.
