Osmotic Stabilization Prevents Cochlear Synaptopathy After Blast Trauma

[Aaron123]

Very interesting paper out of John Oghalai's lab along with Brian Applegate. It may provide some insight into how synapses are damaged and a way to fix it. Please note, this is basic science research in mice so there is no trial scheduled, no drug, no timeline, just perhaps some insight into how the damage occurs.

Significance
Trauma due to roadside bombs is an unfortunate consequence of modern warfare and terrorist attacks. Hearing loss often occurs because the cochlea is the body's most sensitive pressure transducer. Here, we used in vivo imaging of the mouse cochlea using optical coherence tomography to show that increased endolymph volume correlates with damage to the auditory synapse. Reducing endolymph volume by increasing perilymph tonicity treated the synaptic loss. Therefore, this study identifies a treatment for noise-induced hearing loss. Furthermore, it suggests that this treatment may help patients with Meniere's disease, a disabling syndrome of vertigo and hearing loss due to increased endolymph volume.


Abstract
Traumatic noise causes hearing loss by damaging sensory hair cells and their auditory synapses. There are no treatments. Here, we investigated mice exposed to a blast wave approximating a roadside bomb. In vivo cochlear imaging revealed an increase in the volume of endolymph, the fluid within scala media, termed endolymphatic hydrops. Endolymphatic hydrops, hair cell loss, and cochlear synaptopathy were initiated by trauma to the mechanosensitive hair cell stereocilia and were K+-dependent. Increasing the osmolality of the adjacent perilymph treated endolymphatic hydrops and prevented synaptopathy, but did not prevent hair cell loss. Conversely, inducing endolymphatic hydrops in control mice by lowering perilymph osmolality caused cochlear synaptopathy that was glutamate-dependent, but did not cause hair cell loss. Thus, endolymphatic hydrops is a surrogate marker for synaptic bouton swelling after hair cells release excitotoxic levels of glutamate. Because osmotic stabilization prevents neural damage, it is a potential treatment to reduce hearing loss after noise exposure.

Link to paper: http://www.pnas.org/content/early/2018/05/01/1720121115

Other articles/press releases about this: https://cen.acs.org/biological-chemistry/Osmosis-prevent-noise-induced-hearing/96/web/2018/05 and https://news.usc.edu/142599/simple-treatment-may-minimize-hearing-loss-caused-by-loud-noises/

 

[GregCA]

It is great that it is also linked with endolymphatic hydrops and Meniere's... a set of conditions who could also use some help.

 

[Samir]

A little something about noise levels and noise protection in the military:

U.S. soldiers and Marines caught in roadside bombings and firefights in Iraq and Afghanistan are coming home in epidemic numbers with permanent hearing loss and ringing in their ears, prompting the military to redouble its efforts to protect the troops from noise.
...
The Navy and Marines have begun buying and distributing state-of-the-art earplugs, known as QuietPro, that contain digital processors that block out damaging sound waves from gunshots and explosions and still allow users to hear everyday noises. They cost about $600 a pair.
...
In any case, hearing protection has its limits. While damage can occur at 80 to 85 decibels - the noise level of a moving tank - the best protection cuts that by only 20 to 25 decibels. That is not enough to protect the ears against an explosion or a firefight, which can range upwards of 183 decibels, said Dr. Ben Balough, a Navy captain and chairman of otolaryngology at the Balboa Navy Medical Center in San Diego.

https://www.cbsnews.com/news/hearing-loss-now-a-military-epidemic/

Conversely, inducing endolymphatic hydrops in control mice by lowering perilymph osmolality caused cochlear synaptopathy that was glutamate-dependent, but did not cause hair cell loss. Thus, endolymphatic hydrops is a surrogate marker for synaptic bouton swelling after hair cells release excitotoxic levels of glutamate.

I have often seen references to "excitotoxic levels of glutamate" when reading about sensori-neural hearing loss. I don't fully understand how this works to be honest. But are we able to hear this? Are we able to "hear the damage" so to speak?

My tinnitus is most definitely caused by acoustic trauma, and for a short period of time before my tinnitus became constant and right before I started hearing the clicks in my ears, I recall hearing what I would best describe as a frying egg. Usually when I went to bed at night and laid down with the back of my head on the pillow, I would hear this kind of "tsss... tsss..." sound in my left ear, playing like that intermittently until I fell asleep. It was like some kind of release of pressure or whatever. I am convinced it was not an auditory hallucination, but I have no way of proving it either. Just my two cents! I think it was the hair cells or nerves/neurons dying off. Then came the clicks and tonal tinnitus, and these other sounds went away.

Along with these frying egg sounds I also had a static or hissing sound, and that was the first indication of damage I think, but it did not bother me at all. It most likely takes some time for everything to degenerate to the point of developing full tinnitus experience.

Either way, this is a very good and important find! Now we just need to make this imaging instrument available for clinical use. It could be valuable in setting a diagnosis and selecting a treatment.

 

[Steven__]

A little something about noise levels and noise protection in the military:



I have often seen references to "excitotoxic levels of glutamate" when reading about sensori-neural hearing loss. I don't fully understand how this works to be honest. But are we able to hear this? Are we able to "hear the damage" so to speak?

My tinnitus is most definitely caused by acoustic trauma, and for a short period of time before my tinnitus became constant and right before I started hearing the clicks in my ears, I recall hearing what I would best describe as a frying egg. Usually when I went to bed at night and laid down with the back of my head on the pillow, I would hear this kind of "tsss... tsss..." sound in my left ear, playing like that intermittently until I fell asleep. It was like some kind of release of pressure or whatever. I am convinced it was not an auditory hallucination, but I have no way of proving it either. Just my two cents! I think it was the hair cells or nerves/neurons dying off. Then came the clicks and tonal tinnitus, and these other sounds went away.

Along with these frying egg sounds I also had a static or hissing sound, and that was the first indication of damage I think, but it did not bother me at all. It most likely takes some time for everything to degenerate to the point of developing full tinnitus experience.

Either way, this is a very good and important find! Now we just need to make this imaging instrument available for clinical use. It could be valuable in setting a diagnosis and selecting a treatment.

I was exactly the same and always heard like Charlie Brown for awhile when people talked

 

[Bobby B]

Not really prevent T - my T started the minute I left the shooting range and hasn't stopped since. It's due to the destruction of those hair cells which isn't fixed by the salt/sugar injection.

About a week later I experienced hearing loss, distortion and H and yes those is due to nerve damage which could be prevented by those injections , but 3 years later the H and sound issue has greatly improved because neurons in nerve cells can regenerate to an extent but not hair cells

 

[jer]

Interesting comments. Thank you! But one thing, they have not totally ruled out nerve damage from tinnitus. As far as I know, they are just not quite sure what causes tinnitus. And maybe the nerve damage prevents the healing process. So it could or could not be related all to each other, that is the problem with these things. In any case, more good news about possible progress in the hearing field. I feel like we are making great strides at the moment.

 

[dingaling]

I'm not convinced to be honest

Depending on the type and intensity of noise, it can cause synaptopathy where the connections at synaptic level between the base of the hair cell and dendrites are lost (e.g. broken/snapped).

I really don't see how an injection of salt into the eardrum (which is nowhere near the basal ganglia) could reverse this but I'm open to be corrected