Journal
NEUROSCIENCE
Volume 269, Issue -, Pages 367-382Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2014.03.020
Keywords
tinnitus; blast; traumatic brain injury; sildenafil (Viagra, Revatio); hyperacusis; rat
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Funding
- US Department of Defense [W81XWH-11-2-0031]
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Blast-induced tinnitus, along with associated auditory impairment and traumatic brain injury, is a primary concern facing military service members. To search for treatment, we investigated the therapeutic effects of sildenafil, a phosphodiesterase-5 inhibitor, given its vasodilatory effects and evidence suggesting its beneficial effects on noise-induced hearing loss. Rats were subjected to three consecutive blast exposures at 22 psi and were monitored for tinnitus using a gap-detection acoustic startle reflex paradigm. Hearing thresholds and detection were tested using auditory brainstem responses and prepulse inhibition, respectively. Blasted rats were either treated with sildenafil or tap water following blast exposure, while age-matched sham control rats were treated with sildenafil and no blast exposure. Our results showed that sildenafil did not effectively prevent acute tinnitus onset and hearing impairment. Instead, sildenafil significantly suppressed high-frequency tinnitus from 3 to 6 weeks after blast exposure and reduced hearing impairment during the first week after blast exposure. Complex results were observed in the startle force data, where sildenafil-treated rats displayed significantly reduced startle force compared to the untreated blasted group, suggesting possible mitigation of traumatic brain injury and suppression of hyperacusis-like percepts. Taken together, sildenafil showed a therapeutic effect on blastinduced tinnitus and audiological impairment in a time-dependent manner. Other regimens such as higher dosage prior to blast exposure and combination with other treatments deserve further investigation to optimize the therapeutic effects. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
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