EXCITATORY AMINO-ACID ANTAGONISTS PROTECT COCHLEAR AUDITORY NEURONS FROM EXCITOTOXICITY

Since ischemic damage in the brain is linked to glutamate excitotoxici ty, the effects of an acute expo sure to glutamate, alpha-amino-3-hydr oxy-5-methyl-4-isoxazole proprionic acid (AMPA) or N-methyl-D aspartat e (NMDA) on the radial dendrites were compared with those occurring af ter a severe cochlear ischemia. Glutamate and AMPA, but not NMDA, prod uced a drastic swelling restricted to the radial dendrites below the i nner hair cells (IHCs). At a concentration of 20 mu M AMPA, a full ele ctrophysiological recovery could be observed in some cochleas after wa shing the drug out. A prior perfusion of 6-7-dinitroquinoxaline-2,3-di one (DNQX, 50 mu M) prevented the 25 mu M AMPA-induced dendritic swell ing. No protective effect of D-2-amino-5-phosphonopentanoate (D-AP5) c ould be observed. In the same way, ischemia (5-40 minutes) resulted in a clear swelling of the radial dendrites. While D-AP5 had no protecti ve effects, 50 mu M DNQX protected most of the radial dendrites from t he ischemia-induced swelling, excepting those contacting the modiolar side of the IHCs. Finally, 50 mu M DNQX + 50 mu M D-AP5 resulted in a nearly complete protection of all the radial dendrites. Altogether, th ese results suggest that the acute swelling of radial dendrites primar ily occurs via AMPA/kainate receptors. However, in radical dendrites c ontacting the inner hair cells on their modiolar side, NMDA receptors maybe also involved. (C) 1994 Wiley-Liss, Inc.