Related Experiment Video
Updated: Jul 18, 2026
Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice
Published on: January 9, 2019
Electrophysiological correlates of progressive sensorineural pathology in carboplatin-treated chinchillas
Mohamed M El-Badry1, Sandra L McFadden
1Otolaryngology Department, Audiology Unit, El-Minia University Hospitals, El-Minia University, El-Minia, Egypt.
Abstract:
Carboplatin produces progressive damage to auditory nerve fibers, spiral ganglion neurons (SGNs) and inner hair cells (IHC) in the chinchilla cochlea but leaves outer hair cells intact. Within 1 h after injection, many afferent terminals beneath IHCs and myelin lamellae surrounding SGN processes are vacuolated. One day after injection, approximately half of the nerve fibers are missing. IHCs are intact at 2 days, but 20-30% are missing at 3 days. We studied the electrophysiological correlates of this progressive morphological damage by recording cochlear microphonics (CM), distortion product otoacoustic emissions (DPOAE), summating potentials (SP), compound action potentials (CAP) and midbrain evoked potentials (IC-EVP) before and 1 h, 12 h, 1 days, 3 days, 5 days, 7 days and 14 days after carboplatin injection (75 mg/kg IP) in four chinchillas. CM and DPOAEs tended to be unchanged or enhanced. CAP and SP showed little change until Day 3, when amplitudes were reduced in all animals and CAP thresholds were elevated by 9 dB; amplitudes declined further between Days 3 and 5 but not thereafter. IC-EVP amplitudes decreased on Days 3 or 5 but thresholds were relatively unchanged. All animals showed some recovery of IC-EVP between Days 7 and 14, including one with 70% enhancement on Day 14. The results indicate that threshold and amplitude measures fail to detect peripheral pathology until some relatively high threshold level of damage has been exceeded. This has important implications for monitoring peripheral damage and interpreting electrophysiological test results in animals and humans.
Insights
Carboplatin damages auditory nerve fibers and spiral ganglion neurons, but electrophysiological tests may not detect this peripheral pathology until significant damage has occurred. This impacts monitoring and interpreting results in both animals and humans.
Area of Science:
- Ototoxicity research
- Neuroscience
- Auditory system physiology
Background:
- Carboplatin chemotherapy is known to cause ototoxicity.
- The specific mechanisms and temporal progression of carboplatin-induced cochlear damage, particularly to neural structures, require further elucidation.
- Understanding the relationship between morphological damage and electrophysiological changes is crucial for accurate assessment.
Purpose of the Study:
- To investigate the progressive morphological and electrophysiological effects of carboplatin on the chinchilla cochlea.
- To correlate structural damage to auditory nerve fibers, spiral ganglion neurons (SGNs), and inner hair cells (IHCs) with changes in electrophysiological measures.
- To determine the sensitivity of various electrophysiological tests in detecting early-stage carboplatin-induced ototoxicity.
Main Methods:
- Chinchillas received a single injection of carboplatin (75 mg/kg IP).
- Morphological assessments of cochlear structures (auditory nerve fibers, SGNs, IHCs, outer hair cells) were performed at various time points post-injection.
- Electrophysiological recordings including cochlear microphonics (CM), distortion product otoacoustic emissions (DPOAEs), summating potentials (SP), compound action potentials (CAP), and midbrain evoked potentials (IC-EVP) were conducted before and after carboplatin administration.
Main Results:
- Carboplatin caused progressive vacuolation of afferent terminals and SGN processes within 1 hour, with significant nerve fiber loss by Day 1.
- Inner hair cell (IHC) loss began around Day 3.
- Electrophysiological measures like CAP and SP showed delayed changes, with significant amplitude reduction and threshold elevation noted around Day 3, indicating a lag in detection of peripheral damage. CM and DPOAEs remained largely unchanged or enhanced.
- Midbrain evoked potentials (IC-EVP) showed amplitude decreases later, with some recovery observed between Days 7 and 14.
Conclusions:
- Electrophysiological measures, particularly CAP and SP, are not sensitive to early peripheral cochlear damage caused by carboplatin.
- Significant morphological damage must exceed a certain threshold before it is reflected in standard electrophysiological test results.
- These findings have critical implications for the interpretation of electrophysiological data and the monitoring of ototoxicity in both preclinical animal models and human patients undergoing carboplatin treatment.
