Related Experiment Video
Updated: Sep 5, 2025
The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
Published on: November 26, 2015
Effects of Combined Gentamicin and Furosemide Treatment on Cochlear Macrophages
Liana Sargsyan1, Austin R Swisher1, Alisa P Hetrick1
1Research Service, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USA.
Abstract:
Combining aminoglycosides and loop diuretics often serves as an effective ototoxic approach to deafen experimental animals. The treatment results in rapid hair cell loss with extended macrophage presence in the cochlea, creating a sterile inflammatory environment. Although the early recruitment of macrophages is typically neuroprotective, the delay in the resolution of macrophage activity can be a complication if the damaged cochlea is used as a model to study subsequent therapeutic strategies. Here, we applied a high dose combination of systemic gentamicin and furosemide in C57 BL/6 and CBA/CaJ mice and studied the ototoxic consequences in the cochlea, including hair cell survival, ribbon synaptic integrity, and macrophage activation up to 15-day posttreatment. The activity of macrophages in the basilar membrane was correlated to the severity of cochlear damage, particularly the hair cell damage. Comparatively, C57 BL/6 cochleae were more vulnerable to the ototoxic challenge with escalated macrophage activation. In addition, the ribbon synaptic deterioration was disproportionately limited when compared to the degree of outer hair cell loss in CBA/CaJ mice. The innate and differential otoprotection in CBA/CaJ mice appears to be associated with the rapid activation of cochlear macrophages and a certain level of synaptogenesis after the combined gentamicin and furosemide treatment.
Insights
Gentamicin and furosemide cause ototoxicity, leading to hair cell loss and inflammation in mice. CBA/CaJ mice show innate otoprotection, unlike C57 BL/6 mice, due to faster macrophage activation.
Area of Science:
- Ototoxicity research
- Neuroscience
- Immunology
Background:
- Aminoglycosides and loop diuretics induce ototoxicity, causing hair cell loss and cochlear inflammation.
- Macrophage activity in the cochlea is crucial but can complicate therapeutic studies if unresolved.
- Understanding differential susceptibility to ototoxic agents is vital for developing otoprotective strategies.
Purpose of the Study:
- To investigate the ototoxic effects of gentamicin and furosemide in C57 BL/6 and CBA/CaJ mice.
- To correlate macrophage activity with cochlear damage severity and hair cell survival.
- To explore the mechanisms behind differential otoprotection observed in CBA/CaJ mice.
Main Methods:
- Administered high-dose systemic gentamicin and furosemide to C57 BL/6 and CBA/CaJ mice.
- Assessed hair cell survival, ribbon synaptic integrity, and macrophage activation up to 15 days post-treatment.
- Analyzed cochlear tissue, focusing on the basilar membrane and macrophage presence.
Main Results:
- Macrophage activity correlated with cochlear and hair cell damage severity.
- C57 BL/6 mice exhibited greater vulnerability and heightened macrophage activation compared to CBA/CaJ mice.
- CBA/CaJ mice showed limited synaptic deterioration relative to outer hair cell loss, suggesting innate otoprotection.
Conclusions:
- Differential otoprotection in CBA/CaJ mice is linked to rapid cochlear macrophage activation and synaptogenesis.
- The study highlights the role of macrophages in ototoxicity and potential protective mechanisms.
- Findings provide insights into mouse strain-specific responses to ototoxic drugs, informing future research.
