Cross-Species Characterization of Peripheral and Central Effects of Occupational and Blast Exposures: Toward a Diagnostic and Therapeutic Testing Framework
Abstract
Active Service Members encounter potentially damaging sounds during the course of their daily operations and mission activities. These sounds may be continuous, such as an aircraft carrier deck, or loud and brief, such as an explosion or gunfire. Service Members and Veterans experience hearing problems at a much higher rate than the typical person, so it is imperative to understand whether different sounds lead to the same damage to the hearing system or whether they will have different types of damage and hearing difficulties. Furthermore, in order to develop treatments for those with hearing problems, it is necessary to use animal models where one can test different drugs and look for changes in the cells and neural circuits involved in hearing. This is not possible in humans. One major obstacle to developing treatments is that studies in animals, especially across species, differ substantially in how they design experiments and measurements. These designs also differ substantially from human studies. One major aim of our proposal is to coordinate sounds and measurements used to test hearing function across species. In the animal models, we will test the differences in hearing changes when animals are exposed to continuous noise, such as that experienced in military and many civilian workplaces, with brief, very loud noise made by a controlled explosive blast. Then we will measure how hearing changes progressively over time. We predict that in blast-exposed animals, the extremely loud blast sound will damage the hearing organ, the cochlea, along with the connections between the sound-sensing hair cells in the cochlea and the rest of the brain. This damage will result in some hearing loss and weaker output from the cochlea. The brain will try to compensate for weaker cochlear signals, leading to unexpectedly large and indiscriminate brain responses despite some hearing loss. In addition, the blast also produces a concussive wave that passes through and damages the brain, and regions necessary for complex sound recognition are particularly vulnerable, such that even compensating for hearing loss may not fully restore hearing function. However, the way that blast damages the brain is unclear and requires further investigation, which we will do in our current proposal by looking for changes in certain proteins related to the damage. By contrast, we predict that the exposure to loud, continuous noise will result in the brain responding less to sounds in order to protect the brain cells and circuits from too much excitement. From our animal studies, we will gain insight into the different ways that the cochlea and brain respond to these two potentially damaging sound types. Our second major aim is to use these data to understand the hearing of human subjects, including those with or without military experience, comparing those who are typically exposed to noisy environments with those who are not. In this way, we can predict how their hearing will change based on the animal studies. This is a critical improvement for the health of current Service Members and Veterans, because untreated hearing loss is correlated with significantly poorer health and mental health outcomes. Moreover, since we will have data from the same sounds and using the same measurements from the rat, chinchilla, and human, successful drug tests in the rat or chinchilla will be much easier to interpret and prepare for testing in humans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110829
Entities
People
- Michael G Heinz
Organizations
- Purdue University
- United States Army