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Abstract
Endolymphatic hydrops, increased endolymphatic fluid within the cochlea, is the key pathologic finding in patients with Meniere’s disease, a disease of episodic vertigo, fluctuating hearing loss, tinnitus, and aural fullness. Endolymphatic hydrops also can occur after noise trauma and its presence correlates with cochlear synaptopathy, a form of hearing loss caused by reduced numbers of synapses between hair cells and auditory nerve fibers. Here we tested whether there is a mechanistic link between these two phenomena by using multimodal imaging techniques to analyze the cochleae of transgenic mice exposed to blast and osmotic challenge. In vivo cochlear imaging after blast exposure revealed dynamic increases in endolymph that involved hair cell mechanoelectrical transduction channel block but not the synaptic release of glutamate at the hair cell–auditory nerve synapse. In contrast, ex vivo and in vivo auditory nerve imaging revealed that synaptopathy requires glutamate release from hair cells but not endolymphatic hydrops. Thus, although endolymphatic hydrops and cochlear synaptopathy are both observed after noise exposure, one does not cause the other. They are simply co-existent sequelae that derive from the traumatic stimulation of hair cell stereociliary bundles. Importantly, these data argue that Meniere’s disease derives from hair cell transduction channel blockade.
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1 University of Southern California, Caruso Department of Otolaryngology – Head and Neck Surgery, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853)
2 University of Southern California, Caruso Department of Otolaryngology – Head and Neck Surgery, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853); Texas A&M University, Department of Biomedical Engineering, College Station, USA (GRID:grid.264756.4) (ISNI:0000 0004 4687 2082)
3 Washington University in St. Louis, Department of Otolaryngology – Head and Neck Surgery, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0004 1936 9350)
4 University of Southern California, Caruso Department of Otolaryngology – Head and Neck Surgery, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853); University of Southern California, Department of Biomedical Engineering, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853)
5 Boys Town National Research Hospital, Center for Sensory Neuroscience, Omaha, USA (GRID:grid.414583.f) (ISNI:0000 0000 8953 4586)