{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T02:10:47Z","timestamp":1740276647927,"version":"3.37.3"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2010,7,16]],"date-time":"2010-07-16T00:00:00Z","timestamp":1279238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives\/Hypothesis:<\/jats:title><jats:p>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\u2010mediated neuronal degeneration. This study tests the hypothesis that interruption of the initial and\/or downstream aspects of excitotoxicity should provide hearing protection in ELH\u2010associated hearing loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design:<\/jats:title><jats:p>This study tests whether riluzole, a glutamate release inhibitor, and dimethylsulfoxide (DMSO), an anti\u2010inflammatory and antioxidant solvent with favorable properties at the level of glutamate receptors, can protect against early\u2010stage hearing loss in a mouse model of ELH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>The<jats:italic>Phex<jats:sup>Hyp\u2010Duk<\/jats:sup><\/jats:italic>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Compared to no treatment, DMSO provided significant hearing protection (<jats:italic>P<\/jats:italic>&lt; .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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>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\u2010associated hearing loss. 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