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Updated: Jul 4, 2026
The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
Published on: November 26, 2015
Time course of apoptotic cell death in guinea pig cochlea following intratympanic gentamicin application
Mitsuya Suzuki1, Munetaka Ushio, Tatsuya Yamasoba
1Department of Otolaryngology Head and Neck Surgery, University of Tokyo, Tokyo, Japan. misuzuki-tky@umin.ac.jp
Conclusions:
The present study showed that the molecular signal that promotes the death of cochlear hair cells (HCs) induced by intratympanic gentamicin application is significant before the manifestation of morphological and functional changes.
Objectives:
The effect of agents that protect the HCs from aminoglycoside ototoxicity is influenced by the timing of their administration. However, morphological, functional and molecular changes in the cochlea in the early stage following aminoglycoside application have rarely been studied. Therefore, we examined the chronological changes in the cochlea following intratympanic gentamicin application.
Materials And Methods:
Small pieces of gelatin sponge soaked with gentamicin (40 mg/ml) were placed on the round window membrane of mature guinea pigs, and the tympanic bulla was filled with gentamicin solution. They were euthanized at 6, 12, 18, 24, and 48 h following gentamicin application. Auditory brainstem responses (ABRs) were measured before gentamicin application and immediately before euthanasia, and the extent of missing and TUNEL-positive HCs was evaluated.
Results:
ABR thresholds significantly increased 18 h or later following gentamicin application, and the loss of HCs was seen at 24 and 48 h. While functional and morphological changes were not evident until 18 h after gentamicin application, substantial amounts of TUNEL-positive HCs appeared at 12 h.
