ELEVATED EXTRACELLULAR GLUTAMATE CONCENTRATIONS INCREASED MALONDIALDEHYDE PRODUCTION IN ANESTHETIZED RAT-BRAIN CORTEX

Oxidative stress is believed to be involved in the damaging mechanism of excitotoxic insult. Thus, we investigated the effect of elevated ex tracellular glutamate levels on malondialdehyde production, a common i ndex of lipid peroxidation, in anesthetized rat brain cortex. Elevatio n of extracellular glutamate levels was achieved either by exogenously perfusing glutamate solutions, or by perfusing L-trans-pyrrolidine-2, 4-dicarboxylate (PDC), a competitive inhibitor of glutamate uptake tra nsporter, through an implanted microdialysis probe. Malondialdehyde le vels in the microdialysates, which were reacted with thiobarbituric ac id, were analyzed by a high performance liquid chromatography system e quipped with a fluorescence detector. Perfusion of glutamate (1.5 and 15 mM) resulted in dose-dependent increases in extracellular malondial dehyde production (as high as a 6-fold increase in malondialdehyde pro duction following perfusion of 15 mM glutamate solution). PDC (3.14 an d 31.4 mM), not only significantly increased the extracellular glutama te levels in a dose-dependent manner, but also dramatically increased malondialdehyde production (as high as 20-fold increase). These result s suggest that excitotoxicity induces oxidative stress in anesthetized rat brain cortex, as evidenced by the glutamate-induced increase in m alondialdehyde production. (C) 1998 Published by Elsevier Science Irel and Ltd.