Mechanism-Based Prevention of Noise-Induced Tinnitus: Protection and Repair of Peripheral Auditory Neuropathy
Abstract
Tinnitus is the “phantom” perception of a sound when that sound is not actually present. Tinnitus is the number 1 Service-related disability for those who served in the Gulf Wars. Noise-induced tinnitus occurs in approximately 40% of all Veterans. It can produce depression, anxiety, insomnia, a reduced quality of life, and impaired social integration, and reduce the ability to redeploy. Our goal is to develop treatments that will prevent chronic tinnitus from being induced by the noises that Service members are exposed to during their service and/or treat tinnitus once it has appeared. Our previous studies identified a way of preventing tinnitus from occurring if the treatment was given before a noise. This systemic pre-treatment (a combination of anti-excitotoxicity agents Piribedil, Memantine, and antioxidants) reduced the number of rats that developed tinnitus following a small arms fire-like impulse noise. While this was an exciting result, treatment before a noise may not always be feasible for Service members in the field. Our first two aims are therefore designed to test a different treatment approach that could be applied after the exposure to noise. This approach is to provide for “repair”; the effect of the noise is not “prevented,” but instead the noise-induced damage is repaired and brought back to the pre-noise state. Our proposed studies will first determine if such repair can prevent tinnitus from occurring if it begins within 1 day following the noise (Aim 1). We will test two military-relevant noise exposures, a small arms fire-like impulse noise and blast. The treatment to induce repair is to elevate a neurotrophic factor (NT-3) in the cochlea by local delivery (in poloxamer). Next, we will begin to examine the time window for effective treatment (Aim 2), how long after the noise can reconnection be induced by elevating NT-3 and can the later repair either prevent tinnitus from appearing or reverse it and cure tinnitus even after it has occurred. This would have widespread utility to Service members as well as the general public, which is also at risk for noise-induced tinnitus. Finally, our third aim will determine if results from our previous study showing pre-treatments that protect against small arms fire-like impulse noise damage to the inner ear will also protect from blast-induced damage and thereby also prevent blast-induced tinnitus from appearing.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710171
Entities
People
- Richard Altschuler
Organizations
- United States Army
- University of Michigan