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The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
12:21

The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration

Published on: November 26, 2015

Cochlear structure and function after round window application of ototoxins

Carol A Bauer1, Thomas J Brozoski

  • 1Division of Otolaryngology, School of Medicine, Southern Illinois University, P.O. Box 19662, Springfield, IL 62794-9662, USA. cbauer@siumed.edu

Hearing Research
|February 22, 2005
PubMed

Insights

Carboplatin selectively damages inner hair cells (IHCs) in chinchillas, while cisplatin causes outer hair cell (OHC) damage, often with accompanying IHC damage. This study quanties dose-dependent ototoxicity in the cochlea.

Area of Science:

  • Ototoxicity research
  • Auditory neuroscience
  • Mammalian cochlear physiology

Background:

  • Topical round window application of ototoxic agents is a key method for studying cochlear damage and hearing loss.
  • Species-specific differences in cochlear susceptibility to ototoxicity are well-documented.
  • Carboplatin is known as an inner hair cell (IHC) toxin, and cisplatin as an outer hair cell (OHC) toxin in chinchillas.

Purpose of the Study:

  • To quantify the dose-dependent damage to cochlear hair cells (IHCs and OHCs) in chinchillas following direct round window application of carboplatin or cisplatin.
  • To compare the ototoxic effects of carboplatin and cisplatin in the chinchilla cochlea.
  • To investigate potential applications in tinnitus research.

Main Methods:

  • Direct round window application of varying doses of carboplatin and cisplatin in chinchillas.
  • Detailed cytocochleogram analysis of the entire cochlear duct.
  • Auditory brainstem response (ABR) threshold measurements.

Main Results:

  • Carboplatin (2 and 3 mg/ml) caused significant IHC damage with minimal OHC damage, consistent with prior literature.
  • Cisplatin exhibited more variable effects, and contrary to previous reports, OHC damage was consistently accompanied by IHC damage across tested doses.
  • Dose-dependent hair cell damage was quantified for both agents.

Conclusions:

  • The study confirms carboplatin's selective toxicity to IHCs and highlights variability and concurrent IHC damage with cisplatin's OHC toxicity.
  • Direct round window application provides a valuable model for studying ototoxicity and hearing loss, with implications for tinnitus research.
  • Understanding these differential toxicities is crucial for developing targeted therapeutic strategies for hearing loss and tinnitus.

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