Excitatory amino acid antagonists protect cochlear auditory neurons from excitotoxicity

Since ischemic damage in the brain is linked to glutamate excitotoxicity, the effects of an acute exposure to glutamate, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole proprionic acid (AMPA) or N‐‐methyl‐D aspartate (NMDA) on the radial dendrites were compared with these occurring after a severe cochlear is...

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Veröffentlicht in:Journal of comparative neurology (1911) 1994-03, Vol.341 (2), p.241-256
Hauptverfasser: Puel, J.-L., Pujol, R., Tribillac, F., Ladrech, S., Eybalin, M.
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Sprache:eng
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Zusammenfassung:Since ischemic damage in the brain is linked to glutamate excitotoxicity, the effects of an acute exposure to glutamate, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole proprionic acid (AMPA) or N‐‐methyl‐D aspartate (NMDA) on the radial dendrites were compared with these occurring after a severe cochlear ischemia. Glutamate and AMPA, but not NMDA, produced a drastic swelling restricted to the radial dendrites below the inner hair cells (IHCs). At a concentration of 20 μM AMPA, a full electrophysiological recovery could be observed in some cochleas after washing the drug out. A prior perfusion of 6‐7‐dinitroquinoxaline‐2,3‐dione (DNQX, 50 μM) prevented the 25 μM AMPA‐induced dendritic swelling. No protective effect of D‐2‐amino‐5‐phosphonopentanoate (D‐AP5) could be observed. In the same way, ischemia (5‐40 minutes) resulted in a clear swelling of the radial dendrites. While D‐AP5 had no protective effects, 50 μM DNQX protected most of the radial dendrites from the ischemia‐induced swelling, excepting those contacting the modiolar side of the IHCs. Finally, 50 μM DNQX + 50 μM D‐AP5 resulted in a nearly complete protection of all the radial dendrites. Altogether, these results suggest that the acute swelling of radial dendrites primarily occurs via AMPA/kainate receptors. However, in radial dendrites contacting the inner hair cells on their modiolar side, NMDA receptors may be also involved.
ISSN:0021-9967
1096-9861
DOI:10.1002/cne.903410209