Impact of repeated intranasal gentamicin irrigation on structure and function of the vestibular brainstem.

Abstract

Gentamicin is an aminoglycoside antibiotic that broadly targets Gram-negative bacteria. While gentamicin is a clinically effective antibiotic, it has significant oto- and nephrotoxicity. In human subjects, repeated exposure to gentamicin results in dizziness, tinnitus, and high frequency hearing loss. Gentamicin has similar effects across animal species and through several different routes of delivery, including injection and direct deposits in the tympanic cavity. Gentamicin can also be administered intranasally to treat sinusitis in humans and this route of delivery is believed to minimize toxic effects. Nonetheless, we hypothesized that intranasal irrigation of gentamicin will result in ototoxicity and impaired auditory and vestibular function similar to systemic delivery. We investigated this hypothesis in Sprague-Dawley rats that received bilateral, intranasal irrigations of a therapeutic dose of gentamicin or saline from postnatal day (P) 21-31. We examined vestibular structure and function in control and gentamicin-exposed rats by assessing performance on a series of sensorimotor tasks, recording vestibular evoked myogenic potentials (VEMPs), and examining number and morphology of neurons in the brainstem vestibular nuclei. Gentamicin-exposed animals had significantly worse performance on sensorimotor tasks, significantly slower VEMPs, and significantly fewer neurons in the vestibular nuclei. Together, our findings indicate that intranasal administration of gentamicin results in impaired auditory and vestibular function consistent with other routes of delivery.