Hydrogen ions kill brain at concentrations reached in ischemia.
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 microliter/min) 150 mM sodium lactate solutions (adjusted to 6.50-4.00 pH) for 20 min into parietal cortex of anesthetized rats. Interstitial pH (pH0) 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 pH0 was less than or equal to 5.30. Nonlethal injections showed only needle tract injuries. Abrupt deterioration of brain acid-base homeostatic mechanisms correlated with necrosis since pH0 returned to baseline more slowly after lethal tissue injections than after nonlethal ones. The slowed return of pH0 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.
D000138:Acidosis / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology*; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000378:metabolism / Q000494:pharmacology; D019344:Lactic Acid; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D007773:Lactates; D019344:Lactic Acid