Gentamicin administration on the stapes footplate causes greater hearing loss and vestibulotoxicity than round window administration in guinea pigs.
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Date
2013-10
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Publisher
Elsevier
Abstract
Clinically, gentamicin has been used extensively to treat the debilitating symptoms of Mèniére’s disease
and is well known for its vestibulotoxic properties. Until recently, it was widely accepted that the round
window membrane (RWM) was the primary entry route into the inner ear following intratympanic drug
administration. In the current study, gentamicin was delivered to either the RWM or the stapes footplate
of guinea pigs (GPs) to assess the associated hearing loss and histopathology associated with each
procedure. Vestibulotoxicity of the utricular macula, saccular macula, and crista ampullaris in the posterior
semicircular canal were assessed quantitatively with density counts of hair cells, supporting cells,
and stereocilia in histological sections. Cochleotoxicity was assessed quantitatively by changes in
threshold of auditory brainstem responses (ABR), along with hair cell and spiral ganglion cell counts in
the basal and second turns of the cochlea. Animals receiving gentamicin applied to the stapes footplate
exhibited markedly higher levels of hearing loss between 8 and 32 kHz, a greater reduction of outer hair
cells in the basal turn of the cochlea and fewer normal type I cells in the utricle in the vestibule than
those receiving gentamicin on the RWM or saline controls. This suggests that gentamicin more readily
enters the ear when applied to the stapes footplate compared with RWM application. These data provide
a potential explanation for why gentamicin preferentially ablates vestibular function while preserving
hearing following transtympanic administration in humans.
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Citation
King, E. B., Salt, A. N., Kel, G. E., Eastwood, H. T., & O’Leary, S. J. (2013). Gentamicin administration on the stapes footplate causes greater hearing loss and vestibulotoxicity than round window administration in guinea pigs. Hearing Research (304). p159-166.