Abstract
Effective personalized therapeutic treatment for hearing loss is currently not available. Cochlear oxidative stress is commonly identified in the pathogenesis of hearing loss based upon findings from excised tissue, thus suggesting a promising druggable etiology. However, the timing and site(s) to target for anti-oxidant treatment in vivo are not clear. Here, we address this long-standing problem with QUEnch-assiSTed Magnetic Resonance Imaging (QUEST MRI), which non-invasively measures excessive production of free radicals without an exogenous contrast agent. QUEST MRI is hypothesized to be sensitive to noise-evoked cochlear oxidative stress in vivo. Rats exposed to a loud noise event that resulted in hair cell loss and reduced hearing capability had a supra-normal MRI R1 value in their cochleae that could be corrected with anti-oxidants, thus non-invasively indicating cochlear oxidative stress. A gold-standard oxidative damage biomarker [heme oxidase 1 (HO-1)] supported the QUEST MRI result. The results from this study highlight QUEST MRI as a potentially transformative measurement of cochlear oxidative stress in vivo that can be used as a biomarker for improving individual evaluation of anti-oxidant treatment efficacy in currently incurable oxidative stress-based forms of hearing loss.
Highlights
Effective personalized therapeutic treatment for hearing loss is currently not available
The results were compared with a “gold standard” biomarker for oxidative stress: ex vivo whole mount preparations of the cochlea labeled for heme oxygenase I19; hair cell loss and hearing loss were evaluated as other markers[20]
The results show that our noise exposure resulted in hair cell damage and hearing loss primarily in the apex and middle regions of unprotected cochleae
Summary
Effective personalized therapeutic treatment for hearing loss is currently not available. The timing and site(s) to target for anti-oxidant treatment in vivo are not clear We address this long-standing problem with QUEnch-assiSTed Magnetic Resonance Imaging (QUEST MRI), which non-invasively measures excessive production of free radicals without an exogenous contrast agent. The results from this study highlight QUEST MRI as a potentially transformative measurement of cochlear oxidative stress in vivo that can be used as a biomarker for improving individual evaluation of anti-oxidant treatment efficacy in currently incurable oxidative stress-based forms of hearing loss. In preclinical studies treatment with anti-oxidants given early in the course of the disease can prevent noise-induced hearing loss[9,10,11] Translating these results into effective treatments for people requires solving the long-standing problem that conventional assays cannot measure cochlear oxidative stress in vivo[12]. The results were compared with a “gold standard” biomarker for oxidative stress: ex vivo whole mount preparations of the cochlea labeled for heme oxygenase I19; hair cell loss and hearing loss were evaluated as other markers[20]
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