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

Abstract

Extracellular lactate concentration rises following ischaemic stroke in both the infarcted area and in the surrounding ischaemic penumbra. We investigated the effect of lactate accumulation on glucose metabolism in cortical slices from guinea pigs initially by varying superfusion medium to tissue volumes. Stable intracellular K + concentrations indicated that a decrease in media/tissue volume did not impair viability of the tissue, but 13C NMR demonstrated that lactate accumulation in the superfusion medium reduced glucose oxidation with inhibition of glial metabolism via pyruvate carboxylase. The concentration of lactate which had accumulated when significant inhibition was observed was ∼0.85 mM. In independent experiments we found that superfusion of brain slices with lactate at this concentration (even using a ‘high-volume’ of superfusion fluid) decreased oxygen consumption by 40±3%. K +-induced depolarisation partially reversed this effect. These results suggest that even low extracellular lactate concentrations may depress metabolic rates in inactive and poorly perfused brain tissue in vivo through inhibition of glial metabolism of glucose.