Sound preconditioning therapy inhibits ototoxic hearing loss in mice
Soumen Roy, … , Tracy S. Fitzgerald, Lisa L. Cunningham
Soumen Roy, … , Tracy S. Fitzgerald, Lisa L. Cunningham
Published November 1, 2013
Citation Information: J Clin Invest. 2013;123(11):4945-4949. https://doi.org/10.1172/JCI71353.
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Categories: Brief Report Otology

Sound preconditioning therapy inhibits ototoxic hearing loss in mice

Abstract

Therapeutic drugs with ototoxic side effects cause significant hearing loss for thousands of patients annually. Two major classes of ototoxic drugs are cisplatin and the aminoglycoside antibiotics, both of which are toxic to mechanosensory hair cells, the receptor cells of the inner ear. A critical need exists for therapies that protect the inner ear without inhibiting the therapeutic efficacy of these drugs. The induction of heat shock proteins (HSPs) inhibits both aminoglycoside- and cisplatin-induced hair cell death and hearing loss. We hypothesized that exposure to sound that is titrated to stress the inner ear without causing permanent damage would induce HSPs in the cochlea and inhibit ototoxic drug–induced hearing loss. We developed a sound exposure protocol that induces HSPs without causing permanent hearing loss. We used this protocol in conjunction with a newly developed mouse model of cisplatin ototoxicity and found that preconditioning mouse inner ears with sound has a robust protective effect against cisplatin-induced hearing loss and hair cell death. Sound therapy also provided protection against aminoglycoside-induced hearing loss. These data indicate that sound preconditioning protects against both classes of ototoxic drugs, and they suggest that sound therapy holds promise for preventing hearing loss in patients receiving these drugs.

Authors

Soumen Roy, Matthew M. Ryals, Astrid Botty Van den Bruele, Tracy S. Fitzgerald, Lisa L. Cunningham

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Figure 1

Sound preconditioning induces HSPs without causing permanent hearing loss.

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Sound preconditioning induces HSPs without causing permanent hearing los...
Mice were exposed to sound preconditioning (8–16 kHz octave band of noise at 90 dB SPL) for 2 hours. (A) Hearing thresholds were measured by ABR. Twenty-four hours after sound exposure, mice had mean TTSs of 9 to 22 dB. Hearing sensitivity returned to pretest levels by 1 week after sound exposure. Asterisks indicate significance between the pretest and 24-hour post-test ABR thresholds (ANOVA, *P < 0.05). (B) Sound exposure did not cause any change in the amplitude of ABR wave I. (C) Cochleas from sound-treated and control mice were collected at 2, 4, 8, and 12 hours after sound exposure. Sound caused the induction of Hsp32 and Hsp70 mRNA in cochleas of sound-treated mice relative to those of untreated (control) mice. Asterisks indicate a significant increase in Hsp mRNA relative to control. (D) Hsp70 induction in response to sound was restricted to the cochlea. Tissues were collected from control and sound-exposed mice 8 hours after sound exposure. Sound exposure induced Hsp70 mRNA in cochlea but not in brain, heart, or kidney. Asterisk indicates a significant increase in Hsp70 mRNA relative to control. Data shown are the means ± SEM.