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Updated: Jul 16, 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
Pattern of cochlear damage caused by short-term kanamycin application using the round window microcatheter method
Yasuyuki Hashimoto1, Satoshi Iwasaki, Kunihiro Mizuta
1Department of Otolaryngology, Hamamatsu University School of Medicine, Hamamatsu city, Japan. hashimot@hama-med.ac.jp
Conclusion:
Short-term local application of kanamycin by the microcatheter method can control the region and severity of drug effect on the cochlea by changing the concentration and administration time.
Objectives:
To investigate the effect of short-term round window administration of kanamycin by the microcatheter method on cochlear stereociliary bundle loss in a guinea pig model.
Materials And Methods:
Two concentrations and two time periods were used for drug administration to the inner ear. In groups of six animals, a total dose of 172.5 mg/ml or 345 mg/ml of kanamycin was instilled at the rate of 0.1 ml/h into the round window niche over either a 1 h or 2 h period by the microcatheter method. One group of six animals received a saline infusion as a control. The animals were sacrificed after 4 days and stereociliary bundle loss was observed by SEM. Functional changes were evaluated by auditory brainstem response.
Results:
With regard to the severity of the damage, higher drug concentrations were associated with more severe effects. The severity of damage was the same when the same total dose was used; however, it was found that when the dose was administered over a longer period, the damage region was wider. The functional changes also corresponded with the morphological changes.
Insights
Short-term microcatheter delivery of kanamycin to the cochlea allows control over drug effects. Adjusting kanamycin concentration and administration time influences the extent and severity of cochlear damage.
Area of Science:
- Ototoxicity research
- Auditory neuroscience
- Pharmacology
Background:
- Kanamycin is an ototoxic antibiotic.
- Understanding localized drug delivery to the cochlea is crucial for minimizing side effects.
- The microcatheter method offers precise control over drug administration.
Purpose of the Study:
- To evaluate the impact of short-term kanamycin administration via microcatheter on cochlear stereociliary bundle loss.
- To investigate the influence of varying kanamycin concentrations and administration durations on ototoxicity in a guinea pig model.
Main Methods:
- Kanamycin was administered to guinea pig cochleae using a microcatheter at concentrations of 172.5 mg/ml or 345 mg/ml.
- Administration occurred over 1-hour or 2-hour periods at a rate of 0.1 ml/h.
- Stereociliary bundle loss was assessed via scanning electron microscopy (SEM), and auditory function was evaluated using auditory brainstem response (ABR).
Main Results:
- Higher kanamycin concentrations resulted in more severe cochlear damage.
- While total dose determined damage severity, longer administration periods led to a wider region of damage.
- Observed morphological changes in stereociliary bundles correlated with functional deficits measured by ABR.
Conclusions:
- Short-term, localized kanamycin application via microcatheter enables control over the extent and severity of cochlear ototoxicity.
- Modulating kanamycin concentration and administration time are key factors in managing cochlear drug effects.
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