Carboplatin-induced early cochlear lesion in chinchillas
Related Experiment Video
Updated: Sep 23, 2026
Cochlear Implantation in the Guinea Pig
Published on: June 15, 2018
Jian Wang1, Dalian Ding, Richard J Salvi
1School of Human Communication Disorders, Dalhousie University, 5599 Fenwick Street, B3H 1R2 Halifax, NS, Canada. wangj4@dal.ca
Abstract:
Carboplatin preferentially damages inner hair cells (IHC) and type I spiral ganglion neurons (SGNs) in the chinchilla; however, the temporal sequence of events leading to the destruction of these structures is poorly understood. To better understand the mechanisms leading up to the destruction of IHCs and type I SGNs, we measured the activity in single auditory nerve fibers for the first 8 h following carboplatin treatment and also monitored the development of histopathologies in SGNs and IHCs using a dose of carboplatin that killed approximately 50% of the IHCs. The spontaneous discharge rate (SDR) showed a slight increase around 3 h post carboplatin followed by a significant decline at 4-5 h. The saturation driven discharge rate (DDR) showed a significant increase 1-5 h post carboplatin. These physiological changes were associated with the formation of small vacuoles in type I afferent terminals and proximal nerve fibers 1-6 h post carboplatin; signs of IHC damage were first observed around 24-48 h. Thus, the neurotoxic effects of carboplatin occur approximately a day before the IHCs are damaged. The large fluctuations in SDR and DDR that occur several hours after carboplatin treatment are most likely due to the neurotoxic effects of carboplatin.
Insights
Carboplatin damages auditory nerve fibers before inner hair cells. Neurotoxic effects on spiral ganglion neurons precede hair cell damage, indicating a distinct temporal sequence in ototoxicity.
Area of Science:
- Ototoxicity and neurobiology
- Auditory system research
Background:
- Carboplatin is known to damage inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs).
- The precise timing and sequence of these damaging events remain unclear.
Purpose of the Study:
- To elucidate the temporal sequence of carboplatin-induced damage to IHCs and type I SGNs.
- To correlate physiological changes in auditory nerve fibers with histopathological alterations.
Main Methods:
- Monitoring single auditory nerve fiber activity for 8 hours post-carboplatin treatment.
- Assessing histopathological changes in SGNs and IHCs.
- Measuring spontaneous discharge rate (SDR) and saturation driven discharge rate (DDR).
Main Results:
- Physiological changes, including SDR fluctuations and DDR increase, occurred within 1-5 hours post-treatment.
- Histopathological signs of neurotoxicity, such as vacuole formation in afferent terminals, were observed 1-6 hours post-treatment.
- IHC damage was evident significantly later, around 24-48 hours, indicating neurotoxicity precedes hair cell damage.
Conclusions:
- Carboplatin's neurotoxic effects on SGNs and their afferent fibers manifest before observable damage to IHCs.
- Auditory nerve fiber dysfunction occurs approximately 24 hours before inner ear hair cell damage, highlighting a critical temporal window in carboplatin ototoxicity.
More Related Videos
09:06Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice
Published on: January 9, 2019
12:21The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
Published on: November 26, 2015
