Premium
Pharmacological protection of hearing loss in the mouse model of endolymphatic hydrops
Author(s) -
Melki Sami J.,
Heddon Chris M.,
Frankel Jonathan K.,
Levitt Alex H.,
Momin Suhael R.,
Alagramam Kumar N.,
Megerian Cliff A.
Publication year - 2010
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.21018
Subject(s) - excitotoxicity , riluzole , spiral ganglion , medicine , ototoxicity , hearing loss , glutamate receptor , auditory brainstem response , cochlea , edaravone , audiometry , pharmacology , audiology , receptor , chemotherapy , cisplatin
Abstract Objectives/Hypothesis: Excitotoxic and related inflammatory injury are implicated in the spiral ganglion degeneration seen with Meniere's disease and endolymphatic hydrops (ELH). Excitotoxicity is initiated with glutamate elevation and associated with downstream increases in reactive oxygen species resulting in inflammation‐mediated neuronal degeneration. This study tests the hypothesis that interruption of the initial and/or downstream aspects of excitotoxicity should provide hearing protection in ELH‐associated hearing loss. Study Design: This study tests whether riluzole, a glutamate release inhibitor, and dimethylsulfoxide (DMSO), an anti‐inflammatory and antioxidant solvent with favorable properties at the level of glutamate receptors, can protect against early‐stage hearing loss in a mouse model of ELH. Methods: The Phex Hyp‐Duk mouse spontaneously develops ELH and postnatal hearing loss. Starting at postnatal day 6 (P6), daily injections of riluzole + DMSO or just DMSO were administered. Untreated mutants served as controls. At P21, P25, and P30, hearing function was assessed by recording auditory brainstem responses. A cochlear function index was developed to assess global cochlear function at each time point. Results: Compared to no treatment, DMSO provided significant hearing protection ( P < .05). The riluzole + DMSO also showed protection, but it was statistically indistinguishable from DMSO alone; a synergistic increase in protection with riluzole was not observed. Conclusions: This study demonstrates pharmacological hearing protection in an animal model of ELH. The results support the assertion that inflammatory (reactive oxygen species) injury, which is part of the excitotoxic pathway, contributes to the development of ELH‐associated hearing loss. Laryngoscope, 2010