Oxidative Stress Poster Session



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Involvement of NMDA receptors in the glutamate-induced hydroxyl radical production and neurodegeneration in the rat striatum.

Lancelot, E. (Laboratoire de Pharamcologie, UniversitÚ RenÚ Descartes, France)
Callebert, J. (Laboratoire de Pharmacologie, UniversitÚ RenÚ Descartes, France)

Contact Person: Jacques Callebert (michel.masella@lrb.ap-hop-paris.fr)


In the present study we reported, by the use of a microdialysis technique, a massive hydroxyl radical production in the rat striatum during a 500 mM glutamate perfusion. Glutamate also produced a substantial striatal lesion of approximately 24 mm3. The blockade of NMDA receptors by systemically administered dizocilpine (5 mg/kg, i.p.) resulted in a reduction of both hydroxyl radical formation and tissue injury. In this experiment, the glutamate-induced necrosis correlated positively with the amount of hydroxyl radicals produced during the perfusion. Moreover, dizocilpine exerted a similar antioxidant and neuroprotective effect toward a 10 mM NMDA perfusion. On the contrary, when dizocilpine (100 Ám) or 2-amino-5-phosphonopentanoic acid (300 ÁM), two NMDA receptor antagonists, were given through the microdialysis probe, they did not modify the volume of the lesion although they reduced significantly the hydroxyl radical formation. This discrepancy may be the consequence of a limited diffusion of the drugs to the outer areas of the lesion which are more susceptible to be protected. Taken together, these results demonstrate that NMDA receptors are really implicated in the hydroxyl radical production and in the neurodegeneration induced by glutamate.

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Poster Number PAlancelot 0162
Keywords: glutamate, NMDA receptors, hydroxyl radicals, striatum, microdialysis

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Lancelot, E.; Callebert, J.; (1998). Involvement of NMDA receptors in the glutamate-induced hydroxyl radical production and neurodegeneration in the rat striatum.. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/oxidative/lancelot0162/index.html
© 1998 Author(s) Hold Copyright