Recurrent glutamate stimulations potentiate the hydroxyl radicals responseto glutamate

Neurotoxicity induced by hydroxyl radicals (.OH) release is thought to be i nvolved in a number of acute and chronical neuropathologies of the central nervous system. As far as neurodegenerative processes are concerned, the po ssible mechanisms giving rise to such .OH releases remain poorly understood . In the present study, unanesthetized rats were perfused with a low salicy late solution through a chronic microdialysis cannula implanted into the st riatum, and the .OH responses to glutamate were analyzed. A single bolus of 3 mM glutamate elicited only minute releases of,OH in naive rats. By contr ast, recurrent infusions at 1-week intervals of the same glutamate concentr ation induced a robust .OH response. Similar potentiation of the initial re sponse also occurred for a larger glutamate concentration (30 mM), Opposite ly, multiple injections of a high (300 mM) glutamate concentration resulted in a slow down of the initial .OH response recorded in naive animals. The mechanisms giving rise to such effects are presently unknown. It is, howeve r, clear that repetitive dysfunctions of the glutamate neurotransmission ma y be sufficient to promote the release of significant amounts of hydroxyl r adicals, resulting in a progressive impairment of the astrocytic glutamate transporter, leading to neurodegenerative processes. J, Neurosci. Res. 56:1 60-165, 1999, (C) 1999 Wiley-Liss, Inc.