Hearing loss and glutamate efflux in the perilymph following transient hindbrain ischemia in gerbils

The mechanism underlying ischemia-induced hearing loss was studied in gerbi ls with transient hindbrain ischemia. Occlusion of the vertebral arteries c aused an increase in the concentration of glutamate in the perilymph and el evated the compound action potential (CAP) threshold to 24.6 dB at 5 minute s, the CAP threshold subsequently recovered on reperfusion, gradually reach ing 8.3 dB 120 minutes after reperfusion. Under electron microscopy, affere nt dendrites of the cochlear nerve in contact with inner hair cells exhibit ed abnormal swelling 5 minutes after ischemia/reperfusion. These morphologi cal changes were not observed in cochleas treated with an alpha-amino-3-hyd roxy-5-methyl-4-isoxazo propionic acid (AMPA)/kainate-type glutamate recept or antagonist, 6-7-dinitroquinoxaline-2,3-dione (DNQX), before hindbrain is chemia; an N-methyl-D-aspartate (NMDA)-type receptor antagonist, D-2-amino- 5-phosphonopentanoate (D-AP5), was ineffective. Moreover, the histopatholog ical alterations noted 5 minutes after reperfusion were spontaneously ameli orated 120 minutes after ischemia/reperfusion. These findings suggest that the ischemia-induced increase in extracellular glutamate concentration with subsequent activation of AMPA/kainate receptors is responsible for neurite degeneration and hearing loss in the early stages following transient hind brain ischemia. (C) 2000 Wiley-Liss, Inc.