Differential vulnerability of inner and outer hair cell systems to chronicmild hypoxia and glutamate ototoxicity: Insights into the cause of auditory neuropathy

Objective: To describe the effects of long-term mild hypoxia and of glutama te poisoning on the functional properties of the cochlea. Methods: Outer hair cell activity was monitored using otoacoustic emissions and cochlear microphonics, and inner hair cell/cochlear afferent function was measured using neural responses (cochlear action potentials or auditory brainstem responses [ABRs]). Results: In contrast to the effects of acute anoxia, in which all aspects o f cochlear function are simultaneously lost, mild, long-term hypoxia result s in a clear differential effect on outer versus inner hair cell systems. D uring a 2-hour period of mild hypoxia, ABR amplitude and threshold deterior ate significantly, whereas outer hair cell function, as reflected by otoaco ustic emissions, shows Little or no change. A similar dissociation between inner and outer hair cell function is observed during instillation of gluta mate (1-10 mM), where the cochlear microphonic and the otoacoustic emission s are unchanged, whereas cochlear action potential amplitudes are reduced. Conclusion: These studies demonstrate a difference in vulnerability of inne r and outer hair cell systems. The inner hair cell/cochlear afferent system is vulnerable to long-term, mild hypoxia; this may be an etiologic factor in hearing loss of cochlear origin, particularly in high-risk birth infants with auditory neuropathy.