Lactate-induced inhibition of glucose catabolism in guinea pig cortical brain slices

Extracellular lactate concentration rises following ischaemic stroke in bot h the infarcted area and in the surrounding ischaemic penumbra. We investig ated the effect of lactate accumulation on glucose metabolism in cortical s lices from guinea pigs initially by varying superfusion medium to tissue vo lumes. Stable intracellular K+ concentrations indicated that a decrease in media/tissue volume did not impair viability of the tissue, but C-13 NMR de monstrated that lactate accumulation in the superfusion medium reduced gluc ose oxidation with inhibition of glial metabolism via pyruvate carboxylase. The concentration of lactate which had accumulated when significant inhibi tion was observed was similar to 0.85 mM. In independent experiments we fou nd that superfusion of brain slices with lactate at this concentration (eve n using a 'high-volume' of superfusion fluid) decreased oxygen consumption by 40 +/- 3%. K+-induced depolarisation partially reversed this effect. The se results suggest that even low extracellular lactate concentrations may d epress metabolic rates in inactive and poorly perfused brain tissue in vivo through inhibition of glial metabolism of glucose. (C) 1999 Published by E lsevier Science Ltd. All rights reserved.