Lactate reduces glutamate-induced neurotoxicity in rat cortex

Experiments were carried out to test the hypothesis that lactate reduces th e neurotoxicity of glutamate in vivo. MAP2 immunohistochemistry was used to measure lesion size, and microdialysis to measure the changes in glucose a nd lactate in the extracellular compartment. After implantation of a microd ialysis probe 100 mM glutamate with or without 6 mM lactate was added to th e perfusion medium and infused into the cortex of unanesthetized rats. Infu sion of 100 mM glutamate for a period of 30 min produced a lesion of 6.05 /- 0.64 mmm(3), an increase in lactate of 124 +/- 19% above basal and a 21 +/- 9% reduction of glucose below basal level. When 6mM L-lactate was perfu sed together with 100 mM glutamate there was a significant reduction in the size of the lesion and there was no reduction in dialysate glucose. When L -lactate was replaced with D-lactate the lesion size and the increase in di alysate lactate were greater than after glutamate alone. The neuroprotectiv e role Of L-lactate is attributed to its ability to meet the increased ener gy demands of neurones exposed to high concentrations of glutamate. (C) 200 1 Wiley-Liss, Inc.