Physiological and anatomical changes following demyelination of the auditory nerve in chinchillas

The goals of this study were to develop a reliable method of demyelinating the auditory nerve in chinchillas and to study the physiological effects resulting from such demyelination. Further, we wanted to test the hypothesis that auditory nerve demyelination might be the pathological mechanism underlying auditory neuropathy (AN). Chinchillas received a dose of either Adriamycin, a cytotoxic agent, or a sham (vehicle only) injection into the auditory nerve bundle near the cochlear nucleus. The cochlear microphonic (CM), compound action potential (CAP), and inferior colliculus evoked potentials (IC-EVPs) were recorded before and up to 2 months after injection. In addition, distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs) were also recorded. The control group, receiving the sham injection, showed no significant anatomical or physiological changes over the 2-month test period. None of the experimental animals demonstrated significant hair cell loss through the entire study period. Consistently, both the CM and DPOAEs were preserved with even enhanced amplitudes, especially for the CM. Demyelination of the ganglion cells in the modiolus (GC) and the auditory nerve fibers in the internal auditory canal (ANF) began by the first day after the injection and remained for the entire 2-month study period. However, not all experimental animals exhibited the same degree of demyelination. In 40% of the experimental animals (subgroup I), demyelination was severe enough to be detected through light and electron microscopic examination in both GC and ANF. Subgroup I showed substantial threshold elevation, amplitude reduction, and latency prolongation of the CAP and IC-EVPs beginning by the first day after drug injection. While there was progressive deterioration in the CAP over time, some recovery occurred for the IC-EVPs. ABR was absent by the first day and remained absent for the entire study period. On the other hand, 60% of the experimental animals (subgroup II) showed only electron microscopic demyelination of the ANF along with minor physiological changes. The results introduce a potential animal model of auditory nerve demyelination with physiological results that mimic those in AN.