NIH-WRAIR investigation homes in on inner ear effects of explosive blasts

NIH-WRAIR investigation homes in on inner ear effects of explosive blasts

August 4, 2021

Among other health effects, encountering the explosive devices widely deployed in military conflicts can cause long-lasting hearing and balance difficulties. A recent collaboration between the National Institutes of Health Intramural Research Program (IRP) and the Walter Reed Army Institute of Research has produced important insights into the biological basis of those disabilities, which could eventually lead to better methods of preventing and treating them.

Nearly half of American military deaths and 80% of injuries during the wars in Afghanistan and Iraq have been related to home-made bombs called ‘improvised explosive devices’ (IEDs). Even when the heat and debris released by an IED doesn’t cause apparent bodily harm, the detonation can still produce a ‘blast wave’ — essentially a fast-moving wall of pressurized air — that can cause less obvious damage to the brain and the delicate biological structures inside the ear involved in hearing and balance. Nearly a million U.S. veterans were receiving disability payments for hearing loss as of 2014, and hearing aids, while certainly helpful, are far from a perfect solution.

“Hearing aids amplify everything, including background noise,” explains Beatrice Mao, PhD, the new study’s first author and a postdoctoral fellow in the lab of IRP senior investigator Matthew Kelley, PhD. “They’re not as good as what your ear can do.”

Despite the prevalence of the problem, little is known about how exactly blast waves lead to hearing and balance difficulties. One reason is that many studies of how these forces affect the body rely on small, home-made ‘blast simulators’ — often made from plastic PVC pipe — that can be highly variable and sometimes do a poor job of approximating real-world explosions. In an attempt to fix this problem, Kelley’s lab teamed up with researchers at Walter Reed who had access to a more advanced blast simulator that was carefully designed by engineers to produce more consistent blast waves that more closely resemble those produced by real-life explosions.

“This allowed, we thought, for a more realistic blast exposure,” Mao explained. “It’s more like an open-field explosive exposure as opposed to having an explosion go off in essentially a plastic coffin that you’re lying in.”

In the new study, mice were exposed to simulated blasts either once or three times, and the researchers assessed the effects on their hearing over the subsequent six months. Unsurprisingly, all the mice initially showed signs of severe hearing loss, and mice exposed to three blasts showed only minimal signs of recovery six months later.

The researchers also examined the sensory cells, known as hair cells, located on the cochlea, the part of the inner ear responsible for converting sounds into electrical signals the brain can interpret. The inner hair cells, which send auditory information to the brain, did not decrease in number after the animals were exposed to blast waves. However, blast exposure did decrease the number of connections between the inner hair cells and the spiral ganglion neurons that serve as the first stop for auditory signals traveling from the inner hair cells to the brain.

In humans, this kind of change could contribute to a phenomenon called ‘hidden hearing loss’ reported by many service members who encounter explosions. This form of hearing loss causes difficulty hearing in noisy environments but does not show up on traditional hearing tests that rely on simple, pure tones produced in quiet surroundings.

“Hidden hearing loss is a relatively recent discovery,” Mao said. “It has to do, not with a loss of cells, but a loss of the cells’ ability to transmit signals. It’s only identified when someone is given a test where they need to detect a specific sound amongst noise.”

While blast exposure did not affect the number of inner hair cells, it did decrease the number of outer hair cells, with much greater and more widespread loss of those cells in mice that experienced three blasts compared to those that experienced one. Outer hair cells play supportive roles in hearing such as pre-amplifying sounds before they reach the inner hair cells, and once lost they cannot grow back. These findings suggest that researchers working on treatments for blast-induced hearing loss might want to focus their efforts on preventing the loss of the outer hair cells or stimulating their regeneration.

The study also found that all mice exposed to blasts had severe damage to their eardrums, which help transfer sound energy to the hair cells in the inner ear. The fact that a single blast ruptured the eardrums but additional blasts still caused even more damage to outer hair cells suggests that extremely loud sounds can damage the inner ear even without passing through the ear drum, such as by sending powerful vibrations to the inner ear through the skull. If this is the case, it would mean that in-ear hearing protection like earplugs may not be enough to protect hearing in some situations.

Finally, the study found that the animals exposed to blasts showed neither obvious behavioral signs of balance problems nor changes to the vestibular hair cells in the inner ear that send balance-related information to the brain. These results suggest that the balance problems some people experience after encountering explosive blasts might be caused by traumatic brain injury or other mechanisms rather than damage to vestibular hair cells.

Kelley and Mao hope their study will help other researchers more tightly focus their efforts to develop prevention and treatment approaches for blast-induced hearing and balance problems, since their results suggest certain blast-induced changes in the ear might be particularly responsible for those issues. Meanwhile, now that the collaboration with Walter Reed has ended, Kelley’s lab will return to what he calls their “bread-and-butter” research area: figuring out the genes and molecules responsible for constructing hair cells in the first place.

“These hair cells are super special cells — they’re the only cells in the body that can detect sound — and we want to understand from a genetic perspective how do you make those cells,” Kelley said. “That’s important not just for understanding how the ear develops, but if we want to force the system to remake those cells, we need to know the genetic pathways that are required to actually build those cells. We’d love to be able to coerce the system into regenerating hair cells, but we don’t know what pathways we need to turn on to do that.”

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