{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:49:58Z","timestamp":1791643798259,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T00:00:00Z","timestamp":1518480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Endolymphatic sac (ELS) pathophysiology in M\u00e9ni\u00e8re's disease (MD) remains poorly understood. We identified from the literature a group of proteins expressed on the ELS and involved in endolymph volume regulation: aquaporin\u20102 (AQP2), vasopressin receptor V2R, sodium potassium chloride cotransporter 2 (NKCC2), and transient receptor potential cation channel V4 (TRPV4). Our objective was to determine whether their ELS expression was altered in MD, to better understand the pathophysiology of endolymphatic hydrops.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Prospective case\u2010control study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Tertiary care center.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects<\/jats:title><jats:p>Twenty\u2010four patients with definite MD undergoing endolymphatic duct blockage surgery were recruited, as well as 23 controls with no history of MD undergoing surgery for vestibular schwannoma (VS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>ELS biopsies and blood samples for plasma arginine vasopressin (AVP) were obtained. Immunohistochemistry for AQP2, V2R, NKCC2, and TRPV4 was performed. Slides were scanned digitally for highly sensitive pixel density analysis by specialized software (VIS; Visiopharm).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Global scores generated by the software represent total and relative protein expression density of 3 staining intensity levels, exclusively on ELS epithelium. AQP2 expression density was significantly elevated in MD compared to VS (<jats:italic>P<\/jats:italic> =. 003). There was no significant difference in plasma AVP, V2R, NKCC2, and TRPV4 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This original study evaluates simultaneous in situ expression of AQP2, V2R, NKCC2, and TRPV4 on the human ELS in MD, with a control group. Our results show only AQP2 upregulation on the ELS of patients with MD. We suggest a constitutively increased expression of AQP2\u00a0in MD, independent of its regulatory axis (AVP\u2010V2R). Acquired regulator sequence mutations could support this model.<\/jats:p><\/jats:sec>","DOI":"10.1177\/0194599818756829","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T08:01:06Z","timestamp":1518508866000},"page":"721-728","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["M\u00e9ni\u00e8re's Disease Pathophysiology: Endolymphatic Sac Immunohistochemical Study of Aquaporin\u20102, V2R Vasopressin Receptor, NKCC2, and TRPV4"],"prefix":"10.1002","volume":"158","author":[{"given":"Marc\u2010Henri","family":"Asmar","sequence":"first","affiliation":[{"name":"University of Montreal Hospital Centre Research Centre (CRCHUM) Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Gaboury","sequence":"additional","affiliation":[{"name":"University of Montreal Hospital Centre Research Centre (CRCHUM) Montreal QC Canada"},{"name":"Department of 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