Inner Ear Pathologies After Cochlear Implantation in Guinea Pigs: Functional, Histopathological, and Endoplasmic Reticulum Stress-Mediated Apoptosis.

Abstract

Objectives: Vestibular dysfunction is one of the most common complications of cochlear implantation (CI); however, the pathological changes and mechanisms underlying inner ear damage post-CI remain poorly understood. This study aimed to investigate the functional and histopathological changes in the cochlea and vestibule as well as endoplasmic reticulum (ER) stress-mediated apoptosis in guinea pigs after CI.

Design: Auditory brainstem response, ice water test, and vestibular evoked myogenic potentials were used to assess cochlear and vestibular function in guinea pigs before and after CI. Histopathological analyses were conducted at various time points post-CI to observe morphological changes in the cochlea and vestibule, as well as the impact of ER stress on these tissues.

Results: After CI, 10.7% (9/84) of the guinea pigs exhibited nystagmus and balance dysfunction. Auditory brainstem response thresholds increased significantly after CI, and air-conducted cervical and ocular vestibular evoked myogenic potential response rates decreased. The ice water test revealed a gradual reduction in nystagmus elicitation rates, along with decreased nystagmus frequency, prolonged latency, and shortened duration. Histopathological analysis of the cochlea revealed fibrous and osseous tissue formation in the scala tympani and a reduction in hair cells and spiral ganglion cells. In the vestibule, alterations included flattening the ampullary crista and disorganized sensory epithelial cells. Transmission electron microscopy revealed pathological changes including cytoplasmic vacuolization and chromatin uniformity in both cochlear and vestibular hair cells. ER stress was prominent in the cochlea, while no substantial stress response was observed in the vestibule.

Conclusions: Our study highlights the various effects of CI surgery on cochlear and vestibular function and morphology in guinea pigs. ER stress-mediated apoptosis may contribute to secondary cochlear damage, whereas the vestibular system demonstrates adaptive responses that preserve cellular homeostasis. These findings provide insights into potential mechanisms underlying inner ear complications post-CI.