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Proc. Natl. Acad. Sci. USA, Published ahead of print May 7, 2018 | https://doi.org/10.1073/pnas.1720121115
Osmotic stabilization prevents cochlear synaptopathy after blast trauma
Jinkyung Kima, Anping Xiaa, Nicolas Grilleta, Brian E. Applegateb, and John S. Oghalaic,1
aDepartment of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA 94305; bDepartment of Biomedical Engineering, Texas A&M University, College Station, TX 77843; and cCaruso Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, CA 90033
1To whom correspondence should be addressed.
aDepartment of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA 94305; bDepartment of Biomedical Engineering, Texas A&M University, College Station, TX 77843; and cCaruso Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, CA 90033
1To whom correspondence should be addressed.
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.
endolymphatic hydrops | in vivo imaging | cochlea | optical coherence tomography | hearing loss
endolymphatic hydrops | in vivo imaging | cochlea | optical coherence tomography | hearing loss
논문정보
- Research article
- 2018년 05월 (BRIC 등록일 2018-05-16)
- 국외 연구진
- 의약학 > 신경의학
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