title: Conservation of endocochlear potential in mice with profound hearing loss induced by co-administration of kanamycin and furosemide.
abstract: Research in mammalian hair cell regeneration is hampered by a lack of in vivo model of adult mouse inner ear injury. In the present study we investigated the effects of a combination of a single dose of aminoglycoside followed by a loop diuretic in adult mice. The auditory brainstem response threshold shift, extent and defining characteristics of the cochlear lesion were assessed and verified at different time points post-treatment. Our data indicated that this drug combination caused the rapid and extensive death of outer hair cells (OHCs). OHC death presented throughout the cochlea that commenced in the basal turn by 24 h and progressed apically. In contrast, inner hair cell (IHC) loss was delayed and mild. Terminal deoxynucleotidyl transferase dUTP nick end labelling-positive nuclei demonstrated that the majority of OHCs died via an apoptotic pathway. Auditory threshold shifts of up to 90 dB SPL indicated a profound hearing loss. In addition, the endocochlear potential (EP) in the drug-treated animals displayed a significant decline at 12 h post-treatment followed by recovery by 48 h post-treatment. Despite this recovery, there was a significant and progressive decrease in strial vascularis thickness, which was predominantly due to atrophy of marginal cells. The present study reproduced an adult mouse model of aminoglycoside-induced hearing loss. The mechanism underlying the recovered EP in the model with extensive hair cell death is discussed.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xiong
authors.forename: Hanqi
authors.initials: H
authors.lastname: Chu
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Huang
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Cui
authors.forename: Liangqiang
authors.initials: L
authors.lastname: Zhou
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Jianling
authors.initials: J
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Chen
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D001309:Auditory Threshold; D016923:Cell Death; D002470:Cell Survival; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D003055:Cochlear Microphonic Potentials / Q000502:physiology*; D004195:Disease Models, Animal; D004232:Diuretics; D004338:Drug Combinations; D016057:Evoked Potentials, Auditory, Brain Stem; D005665:Furosemide; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000648:ultrastructure; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000648:ultrastructure; D034381:Hearing Loss / Q000139:chemically induced* / Q000473:pathology; D007612:Kanamycin; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011500:Protein Synthesis Inhibitors; D013316:Stria Vascularis / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D004232:Diuretics; D004338:Drug Combinations; D011500:Protein Synthesis Inhibitors; D007612:Kanamycin; D005665:Furosemide