{"doi":"10.5281/zenodo.15542656","title":"Mechanisms of endolymphatic hydrops and cochlear synaptopathy after blast trauma","abstract":"Hearing loss occurs after blast exposure. The classical explanation is hair cell death resulting from stereociliary bundle damage. Another cause is excess glutamate release, which leads to cochlear synaptopathy, which affects neural encoding at higher sound intensities. Additionally, endolymphatic hydrops (ELH), which is associated with hearing loss in Meniere’s disease, also occurs after blast exposure and may contribute to hearing loss. Previously, we found that ELH was correlated with cochlear synaptopathy, and application of hypertonic saline to draw H2O out of the endolymph treated ELH and reduced synaptic loss. This raised the possibility that ELH contributes to the development of cochlear synaptopathy. Here, we sought to determine if ELH causes cochlear synaptopathy. We studied wild type (CBACaJ) mice, those without sterociliary bundle stimulation (TectaC1509G/C1509G), and mice lacking hair cell glutamate release (Vglut3KO). We used optical coherence tomography to compare ELH after blast exposure versus hypotonic challenge to isolate ELH from synaptopathy and derive the specific mechanisms at work. These findings were supported by histological sections and transmission electron microscopic imaging of dendritic terminals after blast trauma in wild type mice. We assessed whether glutamate excitotoxicity is necessary for ELH development after blast in Vglut3KO mice. Three out of five Vglut3KO mice lost all cochlear amplification and developed ELH, indicating that hair cell stimulation is necessary to develop ELH after blast trauma, but glutamate release is not. To determine if hair cells were involved in the development of ELH after hypotonic challenge, we applied a hypo-osmotic solution to the round window. ELH developed in wild type, TectaC1509G/C1509G, and Vglut3KO mice, but synaptopathy did not. These findings suggest that ELH is due to an osmotic gradient between perilymph and endolymph, and neither hair cell transduction nor glutamate release are required. Because ELH developed after an osmotic challenge but did not lead to synaptopathy, we explored the relationship between blast, ELH and synaptopathy. After blast exposure, only wild type, but not TectaC1509G/C1509G nor Vglut3KO mice developed synaptopathy. These data show that sterociliary bundle stimulation is necessary for synaptopathy, but insufficient without glutamate release from the hair cell. Overall, our findings reveal that ELH simply reflects the osmotic load within endolymph, relative to perilymph, but is not a cause of synaptopathy.","journal":"Zenodo (CERN European Organization for Nuclear Research)","year":2025,"id":588026,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1001762,"name":"Connie Paik","orcid":"0000-0001-5557-4018","position":1,"is_corresponding":false},{"id":809945,"name":"Patricia M. Quiñones","orcid":"0000-0002-7535-7739","position":2,"is_corresponding":false},{"id":1295490,"name":"Clayton B. Walker","orcid":"0000-0003-1137-9071","position":3,"is_corresponding":false},{"id":408167,"name":"Michael J. Serafino","orcid":null,"position":4,"is_corresponding":false},{"id":1246295,"name":"Dorothy W. Pan","orcid":"0000-0003-4066-7750","position":5,"is_corresponding":false},{"id":780953,"name":"Juemei Wang","orcid":null,"position":6,"is_corresponding":false},{"id":444431,"name":"Grady Phillips","orcid":null,"position":7,"is_corresponding":false},{"id":407140,"name":"Brian E. Applegate","orcid":"0000-0003-2795-5678","position":8,"is_corresponding":false},{"id":427216,"name":"Michael Anne Gratton","orcid":null,"position":9,"is_corresponding":false},{"id":661987,"name":"John S. Oghalai","orcid":"0000-0003-4241-6189","position":10,"is_corresponding":false},{"id":1295804,"name":"M. Fong","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:59:43.096742Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}