Related Experiment Video
Updated: Aug 18, 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
Comparison of vestibular and cochlear ototoxicity from transtympanic streptomycin administration
H H Wanamaker1, N B Slepecky, L K Cefaratti
1Department of Otolaryngology, SUNY Health Science Center at Syracuse, New York, USA.
Hypothesis:
The relative dose-related cochlear and vestibular ototoxicity produced by transtympanically injected streptomycin (SM) compared to that of gentamicin (GM) was assessed.
Background:
Although SM, the first aminoglycoside used transtympanically, is thought to be selectively vestibulotoxic, it has been replaced by GM in current clinical use. Little experimental data exist that directly demonstrate the relative cochlear and vestibular ototoxicity resulting from transtympanic administration of SM compared to GM.
Methods:
Histologic evaluation was performed on inner ears from Mongolian gerbils to study vestibular and cochlear damage. Comparisons were made between animals receiving single (1 x SM) and five daily (5 x SM) injections of SM/Gelfoam-slurry and similarly injected and noninjected controls. These data were compared to results obtained using GM (1 x GM and 5 x GM) reported previously.
Results:
Two weeks after injection, parallel qualitative and quantitative changes were seen in posterior cristae and cochlear sensory epithelia in the 1 x and 5 x SM injected groups, similar to those resulting from GM injections. Statistically significant decreases in number of hair cells were seen when 5 x SM injected ears were compared to 1 x SM injected ears and control ears. Increased damage was seen with increased dosage of each drug. Whenever damage was observed to the posterior crista sensory cells, damage was also seen in cochlear hair cells.
Conclusions:
In this model, SM and GM produced significant cochlear damage when vestibular damage occurred. These results suggest that, in the gerbil, SM and GM are ototoxic but not selectively vestibulotoxic. Increasing the number of transtympanic injections generally increases the damage to sensory hair cells in the posterior crista and the cochlea. A variation in interanimal susceptibility to ototoxic effects exists, but the amount of damage is consistent in cochlear and vestibular hair cells from the same animal. No evidence for selective vestibular ototoxicity from transtympanic SM was found.
Insights
Streptomycin (SM) and gentamicin (GM) both cause cochlear and vestibular ototoxicity in gerbils, with damage increasing with dosage. Neither drug demonstrated selective vestibular toxicity in this study.
Area of Science:
- Ototoxicity research
- Aminoglycoside drug effects
- Inner ear histology
Background:
- Streptomycin (SM), an early transtympanic aminoglycoside, was thought to be vestibulotoxic but is largely replaced by gentamicin (GM).
- Limited experimental data directly compare the cochlear and vestibular ototoxicity of transtympanic SM versus GM.
Purpose of the Study:
- To assess the relative dose-related cochlear and vestibular ototoxicity of transtympanically injected streptomycin (SM) compared to gentamicin (GM).
Main Methods:
- Histologic evaluation of inner ear damage in Mongolian gerbils following single and multiple transtympanic injections of SM/Gelfoam-slurry.
- Comparison of SM-induced damage with previously reported GM-induced damage and noninjected controls.
Main Results:
- Both SM and GM induced parallel qualitative and quantitative changes in vestibular and cochlear sensory epithelia.
- Statistically significant hair cell loss occurred with increased SM dosage, and cochlear damage was observed concurrently with vestibular damage.
- Increased number of transtympanic injections generally increased damage to sensory hair cells in both the posterior crista and cochlea.
Conclusions:
- In this gerbil model, both SM and GM are ototoxic, affecting both cochlear and vestibular systems, and are not selectively vestibulotoxic.
- Higher doses and multiple injections of SM and GM exacerbate damage to sensory hair cells.
- Ototoxicity effects were consistent between cochlear and vestibular hair cells within the same animal, despite interanimal susceptibility variations.
Related Concept Videos
01:13The Cochlea
01:16Anatomy of the Ear
01:15Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations