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Proc Natl Acad Sci U S A. 2018 May 22;115(21):E4853-E4860. doi: 10.1073/pnas.1720121115. Epub 2018 May 7.

Osmotic stabilization prevents cochlear synaptopathy after blast trauma.

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Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA 94305.
Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843.
Caruso Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, CA 90033


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.


cochlea; endolymphatic hydrops; hearing loss; in vivo imaging; optical coherence tomography

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