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Conflicting electrophysiological and anatomical data from drug-impaired guinea pig cochleas
Abstract:
In guinea pigs that had been treated with very large doses of the aminoglycoside amikacin (14 x 450 mg/kg/day, i.m.) clear, short-latency responses to various click stimuli could be recorded at the round window. When the same cochleas were examined histologically, no outer or inner hair cells could be found along the entire length of the basilar membrane, save for a very few outer hair cells remaining at the apex. The response patterns resembled that of the compound action potential, and various characteristics suggest that they were of neural origin. Vestibular function, investigated by electronystagmography during rotation, appeared normal, as did most of the saccular and utricular hair cells. Transmission electron microscopy revealed a significant number of cochlear nerve fibres still innervating the remnants of Corti's organ. In other cochleas with similarly extensive destruction induced by another aminoglycoside (sisomycin, 14 x 125 mg/kg/day, 15 days as well as 3 months post-Rx), no responses could be recorded from the round window. Cochleas that were less affected, with the upper turns preserved, gave only small, long-latency responses. These preliminary observations are confirmed by further experiments now in progress. They suggest that unless a considerable number of inner hair cells remained undetected in the lower basal turn, a possibility that appears highly unlikely, there was either a direct mechanical excitation of cochlear nerve fibres, or an acoustical stimulation of vestibular sense organs.
Insights
Aminoglycoside antibiotics like amikacin can cause severe hearing loss by destroying cochlear hair cells. However, guinea pigs treated with amikacin still showed neural responses, suggesting direct nerve stimulation or vestibular organ involvement.
Area of Science:
- Ototoxicity research
- Auditory neuroscience
- Pharmacology
Background:
- Aminoglycosides are potent antibiotics with known ototoxic side effects.
- High doses of amikacin cause significant damage to cochlear hair cells.
Purpose of the Study:
- To investigate the origin of auditory responses in guinea pigs with severe aminoglycoside-induced cochlear damage.
- To explore potential mechanisms of sound detection in the absence of hair cells.
Main Methods:
- Administered high doses of amikacin and sisomycin to guinea pigs.
- Recorded auditory brainstem responses (ABRs) at the round window.
- Performed histological and transmission electron microscopy of cochleas.
- Assessed vestibular function using electronystagmography.
Main Results:
- Amikacin treatment destroyed most cochlear hair cells but preserved neural responses.
- Responses in damaged cochleas were short-latency and suggested neural origin.
- Sisomycin caused more complete hair cell destruction, eliminating detectable responses.
- Vestibular function and hair cells appeared largely unaffected.
Conclusions:
- Auditory responses can persist despite near-complete hair cell loss.
- Mechanisms may include direct mechanical excitation of cochlear nerve fibers.
- Acoustic stimulation of vestibular sense organs is a possible alternative pathway.
- Further research is needed to confirm these findings.