Developing TNF-a-Mediated Treatment for Blast-Induced Tinnitus
Abstract
Topic Area: Hearing Loss/Dysfunction, Balance Disorders, and/or Tinnitus -- Etiology of injury. Studies to better understand the primary/secondary effects of blast exposure on the auditory systems. Studies to increase the understanding of the mechanisms underlying tinnitus. More than 50,000 U.S. military personnel have been wounded since 2001. Blast injuries account for over 80% of combat-related injuries. Blast-induced neurotrauma and post-traumatic stress disorder are referred to as "signature injuries" of the Global War on Terrorism, with prevalence as high as 16% and 14%, respectively. Though rare in the civilian population, the socio-economic impacts of blast injuries have risen in the public awareness in light of recent tragic Boston Marathon Bombing. Blast-induced tinnitus is the most common sequela of blast injuries and is listed as the number one diagnosis for service-connected disability claims. Of all military personnel who have sustained blast injuries, 70% reported tinnitus symptoms within 72 hours of the exposure, and 43% reported suffering persistent tinnitus 1 month after. The annual cost to compensate Veterans for tinnitus in the United States is nearly $2 billion and rising. Post-traumatic stress disorder and depression are strongly associated with blast-induced tinnitus, and 34% of Veterans with tinnitus carry a diagnosis of post-traumatic stress disorder concurrently. Tinnitus is often intensified by the sounds that trigger "flash-backs," and Service Members who carry both tinnitus and post-traumatic stress disorder diagnoses experience post-trauma stress disorder symptoms more frequently and with greater intensity than Veterans with post-trauma stress disorder but without tinnitus. Tinnitus, referred as "ringing in the ear" in layman s terms, is scientifically defined as sound perception without an external acoustic event. When improvised explosive devices are detonated, the sound level can exceed 140 dB SPL. The intense noise combined with the instantaneous overpressure created by the detonation inflicts injuries both to the ears and to the brain. In the ears, blasts perforate the tympanic membrane and damage hair cells, causing hearing loss. In the brain, blast shockwaves damage the nerve cells causing traumatic brain injury. A potentially important player in blast-induced traumatic brain injury and tinnitus is a protein called tumor necrosis factor alpha (TNF-alpha). It is produced by brain cells in response to insult, such as blast exposure. Once produced, TNF-alpha causes secondary injury and worsens the damage to the brain. In addition, it can make nerve cells overexcited to fire erroneously, which may be the cause of phantom tinnitus perception. We hypothesize that blast-induced increase in TNF-alpha is a major contributor to blast-induced traumatic brain injury, tinnitus, and other neurological impairments. In the proposed research, we will test three TNF-alpha inhibitors to determine (1) whether they reverse blast-induced increase in TNF-alpha expression; (2) whether they attenuate blast-induced traumatic brain injury and abolish blast-induced tinnitus and anxiety disorders; and (3) whether they abolish putative neural correlates of tinnitus. Our immediate goal is to determine whether targeting TNF-alpha is an effective method to treat blast-induced traumatic brain injury, tinnitus, and other brain disorders. Once our hypothesis is validated, we will develop drugs by working with pharmaceutical companies and conduct clinical trials by working with clinicians for the treatment of blast exposure-induced traumatic brain injury, tinnitus, and other cognitive and neurological disorders.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510028
Entities
People
- Shaowen Bao
Organizations
- United States Army
- University of Arizona