Aminoglycoside Ototoxicity: A Human Temporal Bone Study

Hinojosa, Raúl; Nelson, Erik G.; Lerner, Stephen A.; Redleaf, Miriam; Schramm, David

doi:10.1097/00005537-200110000-00025

Cited by 43 publications

(21 citation statements)

References 30 publications

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“…A few human temporal bone studies have described segmental degeneration and/or atrophy of the stria vascularis in deceased donors who were exposed to gentamicin, tobramycin, neomycin, or kanamycin [22, 26, 27]. Similarly, in our study, we found a smaller stria vascularis, mainly at the apical turn, in our CF group .…”

Section: Discussionsupporting

confidence: 85%

Changes in the inner ear structures in cystic fibrosis patients

Pauna

Monsanto

Kurata

et al. 2017

International Journal of Pediatric Otorhinolaryngology

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Objective Although prolonged use of antibiotics is very common in cystic fibrosis (CF) patients, no studies have assessed the changes in both cochlear and peripheral vestibular systems in this population. Methods We used human temporal bones to analyze the density of vestibular dark, transitional, and hair cells in specimens from CF patients who were exposed to several types of antibiotics, as compared with specimens from an age-matched control group with no history of ear disease or antibiotic use. Additionally, we analyzed the changes in the elements of the cochlea (hair cells, spiral ganglion neurons, and the area of the stria vascularis). Data was gathered using differential interference contrast microscopy and light microscopy. Results In the CF group, 83% of patients were exposed to some ototoxic drugs, such as aminoglycosides. As compared with the control group, the density of both type I and type II vestibular hair cells was significantly lower in all structures analyzed; the number of dark cells was significantly lower in the lateral and posterior semicircular canals. We noted a trend toward a lower number of both inner and outer cochlear hair cells at all turns of the cochlea. The number of spiral ganglion neurons in Rosenthal’s canal at the apical turn of the cochlea was significantly lower; furthermore, the area of the stria vascularis at the apical turn of the cochlea was significantly smaller. Conclusions Deterioration of cochlear and vestibular structures in CF patients might be related to their exposure to ototoxic antibiotics. Well-designed case-control studies are necessary to rule out the effect of CF itself.

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Section: Discussionsupporting

confidence: 85%

Changes in the inner ear structures in cystic fibrosis patients

Pauna

Monsanto

Kurata

et al. 2017

International Journal of Pediatric Otorhinolaryngology

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“…It is interesting to note that the pathology and neural degeneration seen in these cat cochleae after several years of deafness appears to be considerably more severe than the alterations one would expect in the human cochlea after equivalent periods of profound deafness even after congenital deafness (e.g., Linthicum and Anderson 1991;Nadol et al 2001). The extent and progression of hair cell loss and SGC degeneration are likely dependent on the extent and rapidity of onset of aminoglycoside-induced damage to the cochlea and possibly also on species-specific differences in neuronal survival patterns (Forge and Schacht 2000;Hinojosa et al 2001;Johnsson et al 1981;McFadden et al 2004;Sone et al 1998). The dosage of aminoglycosides in our experimental design was intentionally higher than would be used clinically to reduce the variability of the results and to provide a reliable model for profound neonatal hearing loss.…”

Section: Cochlear Pathologymentioning

confidence: 97%

Spatial Selectivity to Intracochlear Electrical Stimulation in the Inferior Colliculus is Degraded After Long-Term Deafness in Cats

Vollmer¹,

Beitel²,

Snyder³

et al. 2007

Journal of Neurophysiology

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Vollmer M, Beitel RE, Snyder RL, Leake PA. Spatial selectivity to intracochlear electrical stimulation in the inferior colliculus is degraded after long-term deafness in cats. J Neurophysiol 98: 2588 -2603, 2007. First published September 12, 2007 doi:10.1152/jn.00011.2007. In an animal model of electrical hearing in prelingually deaf adults, this study examined the effects of deafness duration on response thresholds and spatial selectivity (i.e., cochleotopic organization, spatial tuning and dynamic range) in the central auditory system to intracochlear electrical stimulation. Electrically evoked auditory brain stem response (EABR) thresholds and neural response thresholds in the external (ICX) and central (ICC) nuclei of the inferior colliculus were estimated in cats after varying durations of neonatally induced deafness: in animals deafened Ͻ1.5 yr (short-deafened unstimulated, SDU cats) with a mean spiral ganglion cell (SGC) density of ϳ45% of normal and in animals deafened Ͼ2.5 yr (long-deafened, LD cats) with severe cochlear pathology (mean SGC density Ͻ7% of normal). LD animals were subdivided into unstimulated cats and those that received chronic intracochlear electrical stimulation via a feline cochlear implant. Acutely deafened, implanted adult cats served as controls. Independent of their stimulation history, LD animals had significantly higher EABR and ICC thresholds than SDU and control animals. Moreover, the spread of electrical excitation was significantly broader and the dynamic range significantly reduced in LD animals. Despite the prolonged durations of deafness the fundamental cochleotopic organization was maintained in both the ICX and the ICC of LD animals. There was no difference between SDU and control cats in any of the response properties tested. These findings suggest that long-term auditory deprivation results in a significant and possibly irreversible degradation of response thresholds and spatial selectivity to intracochlear electrical stimulation in the auditory midbrain.

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“…The authors reasoned that spiral ganglion degeneration may occur, independent of hair cell damage. Hinojosa et al (2001) reported temporal bone histopathologic findings from two patients treated with gentamicin and tobramycin. Postmortem analysis revealed loss of spiral ganglion neurons and hair cells.…”

Section: Human Temporal Bone Histopathologymentioning

confidence: 99%