Energy metabolism and NAD-NADH redox state in brain slices in response to glutamate exposure and ischemia

Abstract

A comparative study of the effects of excitotoxic levels of glutamate with ischemia on the cerebral energy metabolism and [NAD]/[NADH] ratio was carried out in adult rat brain slices. Glutamate moderately decreased the high energy phosphates and intracellular pH whereas ischemia showed a pronounced decrease in the high energy phosphates and intracellular pH. The [NAD]/[NADH] ratio increased continuously during glutamate exposure whereas an initial reduction and subsequent oxidation occurred during ischemia. Uptake of glutamate prevailed throughout the glutamate exposure to brain slices signifying favorable glial energy levels while efflux occurred during ischemia indicating complete neuronal and glial depolarization. A net synthesis of glutamate was also observed during ischemia. A small but significant increase in lactate may be a result of increased glycolysis during glutamate exposure, on the other hand a large increase in lactate during ischemia suggests a total failure of oxidative metabolism. Our results show that glutamate exposure to brain slices causes a mild energetic stress and an increase in [NAD]/[NADH] ratio whereas predominant inhibition of phosphate metabolites and dual effect on NAD/NADH redox state was observed during ischemia. It is suggested that the NAD/NADH redox state together with phosphate metabolites and intracellular pH of the periinfarct region could provide vital evidence about the possible involvement of glutamate.