title: Tumor Necrosis Factor-α-Induced Ototoxicity in Mouse Cochlear Organotypic Culture.
abstract: Tumor necrosis factor (TNF)-α is a cytokine involved in acute inflammatory phase reactions, and is the primary upstream mediator in the cochlear inflammatory response. Treatment of the organ of Corti with TNF-α can induce hair cell damage. However, the resulting morphological changes have not been systematically examined. In the present study, cochlear organotypic cultures from neonatal mice were treated with various concentrations and durations of TNF-α to induce inflammatory responses. Confocal microscopy was used to evaluate the condition of hair cells and supporting cells following immunohistochemical staining. In addition, the ultrastructure of the stereocilia bundle, hair cells, and supporting cells were examined by scanning and transmission electron microscopy. TNF-α treatment resulted in a fusion and loss of stereocilia bundles in hair cells, swelling of mitochondria, and vacuolation and degranulation of the endoplasmic reticulum. Disruption of tight junctions between hair cells and supporting cells was also observed at high concentrations. Hair cell loss was preceded by apoptosis of Deiters' and pillar cells. Taken together, these findings detail the morphological changes in the organ of Corti after TNF-α treatment, and provide an in vitro model of inflammatory-induced ototoxicity.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
authors.forename: Guo-Peng
authors.initials: GP
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing Friendship Hospital, Captital Medical University, Beijing, 100050, China.
authors.forename: Jing-Ying
authors.initials: JY
authors.lastname: Guo
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China; Department of Otolaryngology, Head and Neck Surgery, Beijing Friendship Hospital, Captital Medical University, Beijing, 100050, China.
authors.forename: Shu-Sheng
authors.initials: SS
authors.lastname: Gong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology; D015834:Cochlear Diseases / Q000473:pathology; D004195:Disease Models, Animal; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D009924:Organ Culture Techniques; D009925:Organ of Corti / Q000187:drug effects* / Q000473:pathology; D059547:Stereocilia / Q000187:drug effects* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha