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Here, we first establish a strong, dose\u2010dependent association between the severity of sleep disturbance and the degree of hearing loss in a clinical cohort of patients with sudden SNHL. To dissect causal mechanisms, we employ a mouse model of acute sleep deprivation (SD), demonstrating that SD causes a long\u2010lasting, high\u2010frequency hearing loss that, unlike restraint stress, cannot be attributed to generalized systemic stress. The core pathology is a tonotopically restricted cochlear synaptopathy, characterized by loss of hair cell ribbon synapses, initiated by transient oxidative stress and maintained by a chronic, self\u2010sustaining neuroinflammatory program, that drives persistent transcriptional suppression of large\u2010conductance calcium\u2010activated potassium (BK) channels. Tonotopic BK channels suppression is functionally validated by single\u2010cell electrophysiology and closely tracks frequency\u2010specific hearing loss. Critically, pharmacological intervention with the antioxidant N\u2010Acetyl\u2010L\u2010cysteine (NAC) or the BK channel opener NS1619 during the acute phase prevents auditory and synaptic deficits, establishing causal necessity for each pathway node. Together, these findings delineate a causally validated cascade from sleep loss to cochlear pathology, identifying a putative neuroinflammatory memory and BK channels as a therapeutic target for stress\u2010induced sensory neuropathy.<\/jats:p>","DOI":"10.1002\/advs.77570","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:58:57Z","timestamp":1788929937000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transient Sleep Deprivation Induces Persistent Auditory Neuropathy via ROS\u2010Initiated Neuroinflammation and BK Channel Suppression"],"prefix":"10.1002","author":[{"given":"Dan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology The Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou 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