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Osmotic stabilization prevents cochlear synaptopathy after blast trauma.

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.
AuthorsJinkyung Kim, Anping Xia, Nicolas Grillet, Brian E Applegate, John S Oghalai
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 115 Issue 21 Pg. E4853-E4860 (05 22 2018) ISSN: 1091-6490 [Electronic] United States
PMID29735658 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Topics
  • Animals
  • Auditory Threshold
  • Cochlea (physiopathology)
  • Cochlear Diseases (physiopathology, prevention & control)
  • Endolymphatic Hydrops (physiopathology)
  • Hair Cells, Auditory (pathology)
  • Hearing Loss, Noise-Induced (physiopathology, prevention & control)
  • Mice
  • Noise (adverse effects)
  • Osmosis

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